Redox-active proteins containing a heme with a Fe atom as a cofactor
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About the Guest(s): Dr. Kristin Hieshetter Dr. Kristin Hieshetter is a seasoned chiropractor and expert in functional health. She has a profound passion for educating people about the human body's amazing capabilities and bringing it to its fullest potential. As the host of Functional Health Radio, she shares her extensive knowledge of cutting-edge health topics and provides actionable advice to help listeners improve their well-being. Dr. Hieshetter is particularly focused on the role of mitochondria in various health conditions and has dedicated much of her work to advancing the understanding and application of functional health principles. Episode Summary: In this enlightening episode of Functional Health Radio, Dr. Kristin Hieshetter delves into the alarming decline in life expectancy in the United States and the surge in chronic diseases among children. Exploring the reasons behind this health crisis, she introduces the audience to the critical role of mitochondria—the energy powerhouses of our cells—and how their dysfunction can lead to various degenerative diseases. Dr. Hieshetter discusses the innovative therapeutic potential of methylene blue, a compound originally used as a textile dye, which has now emerged as a miracle drug for its remarkable effectiveness in treating conditions such as Alzheimer's, Parkinson's, stroke, and mitochondrial dysfunction. She breaks down the biochemistry of methylene blue, its history, and how it can enhance energy production, reduce inflammation, and support neurogenesis. The episode is filled with actionable insights, scientific explanations, and inspirational stories, making it a must-listen for anyone interested in optimizing their health and unlocking the human body's true potential. Key Takeaways: Mitochondria and Health: The importance of mitochondria in energy production and how their dysfunction contributes to chronic diseases. Methylene Blue as a Miracle Drug: The transition of methylene blue from a textile dye to a potent therapeutic agent with applications in treating malaria, brain diseases, and supporting mitochondrial health. Impact on Neurodegeneration: Methylene blue's ability to protect against neurodegenerative diseases, enhance mitochondrial function, and promote new neuronal growth. Scientific Backing: Extensive research supporting methylene blue's effectiveness in reducing free radicals, improving brain function, and aiding recovery from traumatic injuries. Practical Usage Tips: Guidelines for using methylene blue safely and effectively, including dosages and considerations for individuals on specific medications. Notable Quotes: "We are walking around in the most amazing, intelligent, responsive, adapting, and aware system in the world, the human body." "Methylene blue not only protects your mitochondria but enhances the growth of new neurons, the growth of new synapses, and thereby enhances neurogenesis." "In Alzheimer's disease, methylene blue upregulates complex four to help you speed up metabolism so the body can have more energy." "Imagine that—to take methylene blue if you know you've got a leaky gut to protect your heart valves from things like strep and E. coli hanging out in your heart." "Methylene blue reduces lipid peroxidation. What's the most important lipid in your entire body? Your brain." Resources: "Neuroprotection: An Emerging Role for Methylene Blue" - Journal Molecular Neurobiology, June 2018, Volume 55, Pages 5137-51. "Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathway" - Journal FASEB, March 2008. "The Protective Role of Methylene Blue in Alzheimer's Disease via the Mitochondrial Function and Cytochrome c Oxidase" - Journal of Alzheimer's Disease, 2010. Previous episodes of Functional Health Radio discussing methylene blue and the benefits of extra virgin olive oil. Functional Health Mastery Dr. Kristin's passionate and knowledgeable approach makes this episode a compelling listen for anyone interested in functional health and the role of mitochondria in overall wellness. Don't miss out on the invaluable insights—tune in to unlock the secrets to a healthier, more vibrant life. Stay tuned for more impactful episodes on Functional Health Radio!
Note: The views of this podcast represent those of my guest(s) and I. Note: Purpose of these episodes- not at all, for advice or medical suggestions. These are aimed to provide support for peer pharmacists in training in educational and intellectually stimulating ways. Again, these are not at all for medical advice, or for medical suggestions. Please see your local state and board-certified physician, PA or NP, and pharmacist for medical advice and suggestions. -- In this episode of the podcast, we dive into the mystical Kingdom of Cytochrome where drugs and enzymes come to life! Discover the delicate dance of drug interactions through an enchanting allegory featuring characters like Sir Simvastatin and Lady Grapefruit. Perfect for science students and curious minds alike, this story-driven episode makes complex pharmacology concepts easy to grasp and memorable. Tune in for a unique blend of education and entertainment!
Welcome back to the Evolving Wellness Podcast! In this episode, we're diving deep into the intersection of circadian and quantum biology with our special guest, Dr. Alexis J Cowan. Join us as Dr. Cowan shares her incredible journey from battling chronic health issues to discovering the transformative potential of sunlight in healing. From decoding the mysteries of gut microbiomes to unlocking the therapeutic benefits of UV light, this episode offers practical strategies to optimize your metabolic health. Explore beyond the confines of traditional science and embark on a holistic journey toward well-being. Tune in for illuminating discussions, actionable insights, and a roadmap to holistic living. Check Out Dr. Alexis J Cowan Instagram LinkedIn Courses Podcast Youtube Website The key moments in this episode are: 2:34 - Dr. Cowan's personal health story 6:55 - The gut microbiome 8:25 - Mold's effect on your mitochondria 13:53 - Mitochondrial function & UV light 16:35 - Dr. Cowan's PHD research 20:37 - UV light and the microbiome 22:17 - Changing how we study the sun 27:46 - The melanocortin pathway & POMC effects on appetite 30:17 - Healing mold exposure with circadian & quantum biology 35:28 - Healing with the sun 39:03 - Healing in extreme climates 42:42 - Deuterium depletion 44:50 - Working out outdoors vs indoors 48:14 - The shortcomings of the current scientific framework 53:07 - The fallibility of blood labs 55:48 - Our body's water network 58:40 - Cytochrome 4, ATP, and our mitochondria 1:00:56 - Cellular hydration 1:02:15 - Astro Herbalism 1:05:07 - Contacting Dr. Cowan This video is not medical advice & as a supporter to you and your health journey - I encourage you to monitor your labs and work with a professional! ________________________________________ Click here to get all my free guides and product recommendations to get started on your journey! Check out all my courses to understand how to improve your mitochondrial health & experience long lasting health! (Use code PODCAST to save 10%) Sign up for my newsletter to get special offers in the future!
In this episode we combine many of the pharmacy school raps that have complemented to understanding and learning concepts in Pharmacy School. -- Note: Purpose of these episodes- not at all, for advice or medical suggestions. These are aimed to provide support for peer pharmacists in training in educational and intellectual stimulating ways. Again, these are not at all for medical advice, or for medical suggestions. Please see your local state and board certified physician, PA or NP, and pharmacist for medical advice and suggestions. --
Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices
Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices
Welcome to the Cytochrome Hear feed, where you can find all our short audiofiction projects. Link: https://shows.acast.com/cytochrome-hear RSS Feed: https://feeds.acast.com/public/shows/cytochrome-hear
Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices
References JLR 2014 55(6) Pages 1165-1172. JLR 2018 59(6): 1058–1070. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message
Drs Michael S. Saag and Charles W. Flexner discuss the mechanisms of drug-drug interactions and the promise and limitations of longer-acting HIV therapeutics for both treatment and prevention. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/986504). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources HIV Infection and AIDS https://emedicine.medscape.com/article/211316-overview Drug Interactions With Antiretroviral Therapy (ART) https://emedicine.medscape.com/article/2039809-overview Common Drug Interactions With Protease Inhibitors https://emedicine.medscape.com/article/2041624-overview HIV-Protease Inhibitors https://pubmed.ncbi.nlm.nih.gov/9562584/ The Role of Drug Metabolizing Enzymes in Clearance https://pubmed.ncbi.nlm.nih.gov/24392841/ AIDS Clinical Trials Group https://actgnetwork.org/ Ritonavir https://reference.medscape.com/drug/norvir-ritonavir-342627 The Cytochrome P450 Isoenzyme and Some New Opportunities for the Prediction of Negative Drug Interaction In Vivo https://pubmed.ncbi.nlm.nih.gov/29780235/ Boosting https://clinicalinfo.hiv.gov/en/glossary/boosting Cytochrome p450 Structure, Function and Clinical Significance: A Review https://pubmed.ncbi.nlm.nih.gov/28124606/ Darunavir https://reference.medscape.com/drug/prezista-darunavir-342647 Atazanavir https://reference.medscape.com/drug/reyataz-atazanavir-342608 Tenofovir Disoproxil Fumarate https://clinicalinfo.hiv.gov/en/drugs/tenofovir-disoproxil-fumarate/patient The Structure and Mechanism of Drug Transporters https://pubmed.ncbi.nlm.nih.gov/34272696/ Tenofovir Alafenamide (TAF) Clinical Pharmacology https://pubmed.ncbi.nlm.nih.gov/35146360/ Prodrugs for Improved Drug Delivery: Lessons Learned From Recently Developed and Marketed Products https://pubmed.ncbi.nlm.nih.gov/33137942/ Update on Drug-Drug Interaction at Organic Cation Transporters: Mechanisms, Clinical Impact, and Proposal for Advanced In Vitro Testing https://pubmed.ncbi.nlm.nih.gov/33896325/ The Role of Organic Anion Transporting Polypeptides in Drug Absorption, Distribution, Excretion and Drug-Drug Interactions https://pubmed.ncbi.nlm.nih.gov/27783531/ Creatinine Clearance https://pubmed.ncbi.nlm.nih.gov/31334948/ Dolutegravir https://reference.medscape.com/drug/tivicay-tivicay-pd-dolutegravir-999861 Cobicistat https://reference.medscape.com/drug/tybost-cobicistat-999845 Paxlovid https://pubmed.ncbi.nlm.nih.gov/35138785/ Interaction Between Ritonavir and Statins https://pubmed.ncbi.nlm.nih.gov/11959074/ COVID-19 Drug Interactions https://www.covid19-druginteractions.org/checker Cabotegravir https://reference.medscape.com/drug/vocabria-apretude-cabotegravir-1000364 Lenacapavir https://reference.medscape.com/drug/sunlenca-lenacapavir-4000240 Inhibitors of the HIV-1 Capsid, a Target of Opportunity https://pubmed.ncbi.nlm.nih.gov/29782334/ Flip-Flop Pharmacokinetics--Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development https://pubmed.ncbi.nlm.nih.gov/21837267/ Polymeric Biomaterials for Medical Implants and Devices https://pubmed.ncbi.nlm.nih.gov/33465850/ Microneedle Arrays Combined With Nanomedicine Approaches for Transdermal Delivery of Therapeutics https://pubmed.ncbi.nlm.nih.gov/33419118/ Preexposure HIV Prophylaxis https://emedicine.medscape.com/article/2054869-overview
WERU 89.9 FM Blue Hill, Maine Local News and Public Affairs Archives
Producer/Host: Sarah O’Malley This episode explains the function of the CO1 gene, which is used for DNA barcoding animals. The gene codes for part of the protein cytochrome oxidase, which is integral to aerobic respiration and the generation of ATP. It is also idea for barcoding because of its not to fast/not too slow mutation rate. About the host: Sarah O’Malley is an ecologist, naturalist and science communicator passionate about deepening her listeners’ experiences with the natural world. She teaches biology and sustainability at Maine Maritime Academy and is currently collaborating on a guide book to the intertidal zone in the Gulf of Maine. The post The Essential Rhythm 12/11/22: Cytochrome oxidase what? first appeared on WERU 89.9 FM Blue Hill, Maine Local News and Public Affairs Archives.
The Essential Rhythm | WERU 89.9 FM Blue Hill, Maine Local News and Public Affairs Archives
Producer/Host: Sarah O’Malley This episode explains the function of the CO1 gene, which is used for DNA barcoding animals. The gene codes for part of the protein cytochrome oxidase, which is integral to aerobic respiration and the generation of ATP. It is also idea for barcoding because of its not to fast/not too slow mutation rate. About the host: Sarah O’Malley is an ecologist, naturalist and science communicator passionate about deepening her listeners’ experiences with the natural world. She teaches biology and sustainability at Maine Maritime Academy and is currently collaborating on a guide book to the intertidal zone in the Gulf of Maine. The post The Essential Rhythm 12/11/22: Cytochrome oxidase what? first appeared on WERU 89.9 FM Blue Hill, Maine Local News and Public Affairs Archives.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.07.515397v1?rss=1 Authors: Liu, J., Li, W., Li, J., Song, E., Liang, H., Rong, W., Jiang, X., Xu, N., Wang, W., Qu, S., Zhang, Y., Zhang, C.-Y., Zen, K. Abstract: Extracellular miRNAs serve as signal molecules in the recipient cells. Uptake of extracellular miRNAs by the recipient cells and their intracellular transport, however, remains elusive. Here we show RNA phase separation as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ~110nm discrete nanoparticles which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which the majority of miRNAs are in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of Cytochrome b, leading to increase in ATP and ROS reduction in HEK293T cells. Our findings reveal a previously unrecognized mechanism for uptaking and delivering functional extracellular miRNAs into mitochondria. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
The long( a hot week) awaited episode on the death of cells and all things holy. Jk, but for real if you thought this episode was interesting check out the research my interviewee had[One of Ron's many research articles https://rdcu.be/cW75R , https://link.springer.com/article/10.1007/s10495-020-01647-9#citeas]. This episode focuses on the forms of celluar death, it's reason for survival, and the mechanisms that make it work. Enjoy!! Sources https://youtu.be/-vmtK-bAC5E (What is Apoptosis?" The Apoptotic Pathways and the Caspase Cascade) https://youtu.be/luR6mLnMOwg(Cytochrome C, The Middle Child of the Electron Transport Chain) https://www.immunochemistry.com/pages/necrosis-vs-necroptosis-vs-apoptosis#:~:text=Necrosis%20is%20an%20uncontrolled%20and,or%20small%20clusters%20of%20cells. (Necrosis vs Necroptosis vs Apoptosis) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087413/#:~:text=Apoptosis%20is%20described%20as%20an,release%20of%20inflammatory%20cellular%20contents. (Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells)
The human brain has various states which alter our mood, cognitive function, and even physical health. Being in the right state at the right time may dramatically bolster our bodies against diseases such as Alzheimer's and neurodegeneration or optimise our brain functioning. Photobiomodulation (PBM) is a field of study dealing with light and its physical effects or interactions with the body. Vielight's products, which utilise PBM technology, may help address neurodegeneration and a variety of other health concerns. In this episode, Peter Adams, Vice President of Business Development at Vielight, talks about the science and mechanisms of action behind photobiomodulation's health benefits. He also discusses Vielight's products and their therapeutic effects in fighting off neurodegeneration. If you want to learn about photobiomodulation's positive health effects, this episode is for you! Here are three reasons why you should listen to this episode: Understand the benefits of photobiomodulation on brain injuries and other health concerns. Learn PBM's mechanisms of action and the science behind how it works. Discover Vielight's PBM products. Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to https://www.peakwellness.co.nz/epigenetics. Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5 km or run a 100-miler? Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle? Go to www.runninghotcoaching.com for our online run training coaching. Health Optimisation and Life Coaching Are you struggling with a health issue and need people who look outside the square and are connected to some of the world's greatest science and health minds? Then reach out to us through support@lisatamati.com, and we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, contact us at support@lisatamati.com. Order My Books My latest book Relentless chronicles the inspiring journey of how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions worldwide, go to https://shop.lisatamati.com/collections/books. Lisa's Anti-Ageing and Longevity Supplements NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting-edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and the liver. Take charge of your energy levels, focus, metabolism and overall health to live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity, which are rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: https://nmnbio.nz/collections/all NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Quality You Can Trust — NMN Our premium range of anti-ageing nutraceuticals (supplements that combine Mother Nature with cutting-edge science) combats the effects of aging while designed to boost NAD+ levels. Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health Metabolic Health My ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection. Episode Highlights [03:08] What Is Photobiomodulation? Photobiomodulation or PBM utilises the way light physically affects the human body instead of light's effects on our cognitive and mental faculties. Light wavelengths of 600 to 1100 nanometers (nm) have therapeutic purposes. Blue or ultraviolet light is an excellent disinfectant but can't penetrate deeply due to its shorter wavelength. At the red end of the colour spectrum, infrared light may overheat heat or burn cells. There's a sweet spot near the red end that has a nice combination of penetration but without the negative cellular effect. [05:21] How Light Gets into the Body One way to get light into the body is intranasally. There's a profusion of blood cells very close to the surface in the sinuses, so it's a good place to penetrate the blood. Dr Lew Lim, founder and CEO of Vielight, discovered the non-invasive intranasal method. Another path is transcranial using diodes. Vielight's goal has always been to develop and design low-power rechargeable devices that are easy and safe to use at home. Vielight did a study with the Centre for Addiction and Mental Health (CAMH), proving that the whole brain is affected by light diodes. [10:21] Neuro Alpha and Neuro Gamma Vielight's product, Neuro Alpha, pulses at 10 Hz, helping the brain resonate in the alpha wave band. Neuro Gamma, pulsing at 40 Hz, was designed mainly to address the reduction in beta-amyloid plaques, which may be associated with Alzheimer's disease. The effect of the two products has yet to be rigorously scientifically quantified, but users have reported significant benefits. Many sports professionals and psychological trainers use Vielight's products to prepare for a match or game. After Peter was in an accident, Neuro Alpha calmed him down while he had a concussion. He used the Neuro Gamma to help alleviate brain fog while at work. [13:32] Healing Mechanisms of PBM There is an increase in glutamate after a traumatic brain injury, which leads to neurons constantly firing and dying, so glutamate level needs to be controlled post-concussion. Vielight recently completed a study on forty retired athletes with repetitive head injuries at the University of Utah. Pre- and post-fMRIs showed increased blood flow in the brain. One of the key mechanisms of PBM delivered intranasally is a change in the viscosity, which increases microcirculation. PBM also increases nitric oxide and leads to a reduced oxygen species effect. PBM increases adenosine triphosphate (ATP) levels — a good indicator of immune function. The Cytochrome c oxidase leads to increased oxygen at the ATP synthase, which increases ATP production. [35:30] 633 Red, 655 Prime, 810 Infrared and Neuro Pro Vielight's 633 red uses a light-emitting diode (LED), while 655 Prime is a red laser diode with more power and penetration. Both products bioinfuse the blood. 810 Infrared is near the infrared band, and its diode produces a red glow. Near-infrared diodes can go into the deep brain. Neuro Pro uses six diodes and an intranasal. Users control each diode with an app, where they can change the power, pulse frequency, and phase. The device can go from 0 Hz up to 10 kilohertz. Vielight's products can help address neurodegeneration, which can come from repeated brain injuries usually experienced by athletes. [35:30] X-Plus and Neuro Vielight's X-plus has an intranasal and applicator. Users can use it with Neuro devices to reach the back of the head or other body parts. Recently Vielight completed a clinical trial with COVID-positive patients, wherein X-Plus was used to stimulate the immune system of the thymus. X-Plus can also be used to repair wounds from injuries in the bones and muscles. Vielight's Neuro uses four diodes, covering the default mode network of the brain. 7 Powerful Quotes “One of the key mechanisms of photobiomodulation, especially directly into the blood through the nose, is a change in the viscosity, increasing the microcirculation, and also an increase in nitric oxide, which is another great healer as well. And, of course, then there's the reduced oxygen species effect, so inflammation gets affected too. So there's a whole bunch of effects that seem to be happening in parallel.” “I think there's hope for Alzheimer's. I just saw another study with autism come out of Italy using neuro as well, which looks really promising.” “I always caution people to think that photobiomodulation is the answer to Alzheimer's. I think even if you look at, for example, antipsychotic drugs, anticonvulsant drugs, all of them, you're not gonna say that one is going to fix everything, and the chances of one fixing anything is less than 30%. [It's] the hit rate.” “It's my belief that underlying conditions that cause plaque in the brain could come from a myriad of sources, and I think it depends on your own individual profile, or physiological profile and chemical pathogenic profile.” “I think a lot of us have now over-excited brains from brain injuries, from toxins in the environment, from the wrong foods and inflammation, and all of the things that sort of happen. Trying to come down and get it in the right zone at the right time is definitely very, very important.” “...The gamma brainwave state of sleep, when you enter that state, that's the key detox part of the brain at night. And so, there is definitely something there to be sought, I think. If you can do it in meditation during the daytime, I think that's even better.” “There's always another quest to research, and it's really patient-reported outcomes that give us great spirit.” Resources Listen to the podcast episode: Photobiomodulation - What it is and how it helps. With Dr Lew Lim Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron! Pulsed Near-Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study. Find all the Vielight's products discussed in this episode on their website. Vielight's Research & Clinical Trials Study on the effects of the Vielight Neuro Gamma on individuals with sports-related traumatic brain injuries (TBIs) Connect with Peter Adams: Apollo About Peter Peter Adams is the Vice President of Business Development at Vielight. He has worked in executive, consulting and management positions internationally and in Canada, in large corporations and startups, including Fortune 500 companies. His current focus is on early-market development for Vielight Inc. Learn more about Vielight's products on their website. Get to know Peter's professional experience on Apollo. Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can learn about the benefits of photobiomodulation (PBM). Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa
I read from cysteine to cytochrome. The word of the episode is "cystic fibrosis". https://en.wikipedia.org/wiki/Cystic_fibrosis https://www.cff.org/ Theme music from Tom Maslowski https://zestysol.com/ Merchandising! https://www.teepublic.com/user/spejampar "The Dictionary - Letter A" on YouTube "The Dictionary - Letter B" on YouTube "The Dictionary - Letter C" on YouTube Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/ Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar https://www.tiktok.com/@spejampar 917-727-5757
Es braucht etwas mehr als 100 mg Zyanid, um einen 75 kg schweren Menschen zu töten. Etwas mehr als 100 mg und das unglückliche Opfer zeigt die verräterischen Anzeichen von "bläulichen Tönen des Sauerstoffmangels, die die Haut fleckig machen". Zyanidvergiftungen sind so alt wie die Nutzung von chemischen Stoffen mit diesem Bestandteil und diese Episode befasst sich mit der Chemie, die im Körper dabei geschieht. „Dies wird die vorläufig letzte Episode der Alltagschemie sein. Es hat mir sehr viel Spass gemacht, aber aus den üblichen Gründen, muss dieses Hobbyprojekt auf unbestimmte Zeit gestoppt werden. Vielen Dank an alle meine Hörer und Hörerinnen. Eine tolle Erfahrung, die ich nicht missen möchte. Macht es gut. Der Podcast wird bis auf weiteres online bleiben, aber keine neuen Inhalte werden hinzugefügt. Quellen Geschichtlicher Hintergrund · The Poisoner's Handbook: Murder and the Birth of Forensic Medicine in Jazz Age New York, Chapter 3, 2010, D. Blum ISBN: 978-1594202438 Zyanidvergiftungen und Zyanidchemie · https://en.wikipedia.org/wiki/Cyanide_poisoning · https://www.thoughtco.com/overview-of-cyanide-poison-609287 · https://en.wikipedia.org/wiki/Cyanide · https://en.wikipedia.org/wiki/Histotoxic_hypoxia Oxidative Phosphorylierung und Cytochrom C Oxidase · https://en.wikipedia.org/wiki/Cytochrome_c_oxidase#Inhibition · https://en.wikipedia.org/wiki/Oxidative_phosphorylation · https://en.wikipedia.org/wiki/Electron_transport_chain Mitochondrien · https://en.wikipedia.org/wiki/Mitochondrion · https://www.thoughtco.com/mitochondria-defined-373367 Medizinische Behandlung von Zyanidvergiftungen · https://www.drugs.com/cg/cyanide-poisoning.html · https://www.healthline.com/health/cyanide-poisoning
It takes a little bit more than 100mg of cyanide to kill a 75 kg human being. A little more than 100mg and the unfortunate victim will show the telltale signs of “bluish tones of oxygen deprivation mottle the skin.“ Cyanide Poisoning is as old as the usage of chemical compounds containing cyanide and this episode looks at the chemistry that happens in the body during a poisoning. “This will be the last episode of Chemistry in Everyday Life for now. It was a huge amount of fun, but for the usual reasons, I have to suspend this beloved hobby project for an indefinite period of time. I would like to thank you all for listening. I enjoyed this experience immensely and I am proud of what I achieved. Take care everyone
Need a quicker way to learn medical information? Does cytochrome P450 intimidate you? Do you ever feel that it is to difficult to memorize drug interactions to even try? Well, not anymore! My quirky ways of thinking has brought us yet another great way to learn this complex system in a fun, and thorough way!
Dr. Chris McCurdy is the international expert on Kratom. Dr. McCurdy and I discuss this "plant of controversy" in detail. Kratom almost became a schedule one substance in the United States. The work of Chris Bell, Dr. McCurdy and others prevented this. In the podcast, Dr. McCurdy and I delve into the long history of Kratom use in places like Southeast Asia, Kratom benefits, and why the controversial cases involving Kratom should be revisited. Who is Dr. Chris McCurdy? Christopher R. McCurdy, Ph.D. B.S.Ph, FAAPS, professor, Medicinal Chemistry, college of Pharmacy, University of Florida.Christopher McCurdy, Ph.D., is a broadly trained medicinal chemist, behavioral pharmacologist and pharmacist whose research focuses on the design, synthesis and development of drugs to treat pain and drug abuse. For over 20 years, much of his research has focused on opioid, Neuropeptide FF and sigma receptor ligand/probe design, synthesis, pharmacological evaluation and development.Watch below leading research scientist Dr. Chris McCurdy’s eye-opening lecture about Kratom effects and potential positive medical benefits.Highlights[5:01] The kratom controversy[17:34] Kratom metabolism [24:15] Cytochrome p450 family and genetic implications [30:00] Benefits of taking Kratom[40:11] Effects of the 7-Hydroxymitragynine alkaloid[45:38] Current stance from the FDA on KratomResourcesKratom deaths: CDC studyMedicine ManA Leaf of FaithSuspected Adulteration of Commercial Kratom Products with HydroxymitragyineHerbal Medicines for the Management of Opioid AddictionSponsorsB StrongI’ve been fascinated by blood flow restriction training for a very long time. B Strong made great innovations on this technology. I use it almost every day: high reps, low number of sets, a few exercises. In 20 minutes, I have a fantastic workout which is triggering an anabolic response.If you want to get your B Strong blood flow restriction device, head on over to https://bstrong.training/ and use the code BOOMER, and you’re going to get yourself 10% off.Disclaimer This information is being provided to you for educational and informational purposes only. This is being provided as a self-help tool to help you understand your genetics, biodata and other information to enhance your performance. It is not medical or psychological advice. Virtuosity LLC, or Decoding Superhuman, is not a doctor. Virtuosity LLC is not treating, preventing, healing, or diagnosing disease. This information is to be used at your own risk based on your own judgment. For the full Disclaimer, please go to (Decodingsuperhuman.com/disclaimer). See acast.com/privacy for privacy and opt-out information.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.367284v1?rss=1 Authors: Brittain, T. J., O'Malley, M. C., Swaim, C. M., Fink, R. A., Kokhan, O. Abstract: C-type cytochromes play an important role in respiration of dissimilatory metal-reducing bacteria. They form extended conduits for charge transfer between the cellular metabolism and external electron acceptors such as particles of iron oxide, metal ions, and humic substances. Out of more than a hundred c-type cytochromes in Geobacter sulfurreducens, only a small fraction has been previously characterized. Here we present our results on expression and biophysical characterization of GSU0105, a novel 3-heme cytochrome, important for Fe(III) respiration in G. sulfurreducens. We successfully cloned the gene and achieved ~3 mg/L of culture GSU0105 expression in E.coli. Despite a similar size (71 amino acids) and the same number of c-type hemes to the members of the cytochrome (cyt) c7 family, multiple sequence alignment suggests that GSU0105 does not belong to the cyt c7 family. UV-Vis spectroscopy revealed typical c-type cytochrome spectral features, including a weak iron-sulfur charge transfer band suggesting that at least one heme is ligated with a methionine residue. Far UV circular dichroism studies demonstrate approximately 35% content of -helices and {beta}-sheets, each, as well as thermal aggregation occurring above 60C. A combination of SAXS and analytical size exclusion chromatography data shows that GSU0105 is monomeric in solution. Finally, affinity pull-down assays demonstrate high binding affinity to PpcD and weaker binding to the other members of the cyt c7 family. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.14.296467v1?rss=1 Authors: Connick, J. P., Reed, J. R., Cawley, G. F., Backes, W. L. Abstract: Heme oxygenase 1 (HO-1) and the cytochromes P450 (P450s) are endoplasmic reticulum-bound enzymes that rely on the same protein, NADPH-cytochrome P450 reductase (POR), to provide the electrons necessary for substrate metabolism. Although the HO-1 and P450 systems are interconnected due to their common electron donor, they generally have been studied separately. As the expression of both HO-1 and P450s are affected by xenobiotic exposure, changes in HO-1 expression can potentially affect P450 function, and conversely, changes in P450 expression can influence HO-1. The goal of this study was to examine interactions between the P450 and HO-1 systems. Using bioluminescence resonance energy transfer (BRET), HO-1 formed HO-1P450 complexes with CYP1A2, CYP1A1, and CYP2D6, but not all P450s. Studies then focused on the HO-1/CYP1A2 interaction. CYP1A2 formed a physical complex with HO-1 that was stable in the presence of POR. As expected, both HO-1 and CYP1A2 formed BRET-detectable complexes with POR. Whereas the PORCYP1A2 complex was readily disrupted by the addition of HO-1, the PORHO-1 complex was not significantly affected by the addition of CYP1A2. Interestingly, enzyme activities did not follow this pattern. Whereas BRET data suggested substantial inhibition of CYP1A2-mediated 7-ethoxyresorufin deethylation in the presence of HO-1, its activity was actually stimulated at subsaturating POR. In contrast, HO-1-mediated heme metabolism was inhibited at subsaturating POR. These results indicate that HO-1 and CYP1A2 form a stable complex and have mutual effects on the catalytic behavior of both proteins that cannot be explained by simple competition for POR. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.265934v1?rss=1 Authors: Rodriguez-Lopez, C. E., Hong, B., Paetz, C., Nakamura, Y., Koudounas, K., Passeri, V., Baldoni, L., Alagna, F., Calderini, O., O'Connor, S. E. Abstract: Olive (Olea europaea) is an important crop in Europe, with high cultural, economic, and nutritional significance. Olive oil flavor and quality depend on phenolic secoiridoids, but the biosynthetic pathway of these iridoids remains largely uncharacterized. We discovered two novel, bi-functional cytochrome P450 enzymes, catalysing the rare oxidative C-C bond cleavage of 7-epi-loganin to produce oleoside methyl ester (OeOMES) and secoxyloganin (OeSXS), both through a ketologanin intermediary. Although these enzymes are homologous to the previously reported Catharanthus roseus Secologanin Synthase (CrSLS), the substrate and product profiles differ. Biochemical assays provided mechanistic insights into the two-step OeOMES and CrSLS reactions. Model-guided mutations of OeOMES changed the product profile in a predictable manner, revealing insights into the molecular basis for this change in product specificity. Our results suggest that, in contrast to published hypotheses, in planta production of secoxy-iridoids is secologanin independent. Notably, sequence data of cultivated and wild olives, points to a relation between domestication and OeOMES expression. Thus, the discovery of this key biosynthetic gene suggests a link between domestication and secondary metabolism, and could potentially be used as a genetic marker to guide next-generation breeding programs. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.27.269936v1?rss=1 Authors: Bukhdruker, S., Varaksa, T., Grabovec, I., Marin, E., Shabunya, P., Kadukova, M., Grudinin, S., Kavaleuski, A., Gusach, A., Gilep, A., Borshchevskiy, V., Strushkevich, N. Abstract: Spreading of the multidrug-resistant (MDR) strains of the deadliest pathogen Mycobacterium tuberculosis (Mtb) generates the need for new effective drugs. SQ109 showed activity against resistant Mtb and already advanced to Phase II/III clinical trials. Fast SQ109 degradation is attributed to the human liver Cytochrome P450s (CYPs). However, no information is available about interactions of the drug with Mtb CYPs. Here, we show that Mtb CYP124, previously assigned as a methyl-branched lipid monooxygenase, binds and hydroxylates SQ109 in vitro. A 1.25-[A] resolution crystal structure of the CYP124-SQ109 complex unambiguously shows two conformations of the drug, both positioned for hydroxylation of the {omega}-methyl group in the trans position. The hydroxylated SQ109 presumably forms stabilizing H-bonds with its target, i.e., the Mycobacterial membrane protein Large 3 (MmpL3). We anticipate that Mtb CYPs could function as analogs of drug-metabolizing human CYPs affecting pharmacokinetics and pharmacodynamics of antitubercular (anti-TB) drugs. Copy rights belong to original authors. Visit the link for more info
Dr. Francisco Gonzalez-Lima is one of the world's leading neuroscientists and an expert in Cytochrome Oxidase. This is part one of a two part discussion. Dr. Gonzalez-Lima educates on the role of cytochrome oxidase and the history of methylene blue. Who is Dr. Francisco Gonzalez-Lima? Francisco Gonzalez-Lima, Ph.D., is a courtesy professor in the Department of Psychiatry. He also holds the George I. Sanchez Centennial Professorship at The University of Texas at Austin, where he is a professor in the departments of Psychology, Psychiatry, Pharmacology and Toxicology and the Institute for Neuroscience.Gonzalez-Lima’s teaching experience includes undergraduate, medical, graduate and postdoctoral students, and he currently teaches the core graduate course in Functional Neuroanatomy. Gonzalez-Lima has been the research adviser of 22 Ph.D. students at UT Austin, and his trainees are world leaders in brain research on the relationship between brain energy metabolism, memory and neurobehavioral disorders.Gonzalez-Lima graduated with honors from Tulane University in New Orleans with a Bachelor of Science in biology and Bachelor of Arts in psychology, and he earned his doctorate in anatomy and neurobiology from the University of Puerto Rico School of Medicine, which honored him with a Distinguished Alumnus Award. He completed postdoctoral training (behavioral neuroscience) at the Technical University of Darmstadt, Germany, as an Alexander von Humboldt research fellow.Gonzalez-Lima has been a visiting neuroscientist in Germany, England, Canada and Spain and he has delivered more than 120 invited lectures about his brain research around the world. His research has been funded for more than 30 years with federal and private funds, and he has contributed to more than 350 scientific publications in peer-reviewed journals, conference proceedings, chapters and books.Current research in the Gonzalez-Lima laboratory focuses on the beneficial neurocognitive and emotional effects of noninvasive human brain stimulation in healthy, aging and mentally ill populations. This research primarily uses transcranial infrared laser stimulation and multimodal imaging (EEG, fNIRS and fMRI) in collaboration with colleagues at UT Austin, The University of Texas at Arlington and University of Texas Southwestern Medical Center. Gonzalez-Lima supervises and trains students and residents to contribute to these ongoing brain research projects.Highlights[17:13] Cytochrome oxidase as a marker for longevity[25:14] Dr. Gonzalez-Lima's journey into methylene blue[37:20] What is the history of methylene blue?[39:40] Magic Bullet[44:36] Methylene Blue dosingResourcesMethylene Blue Preserves Cytochrome Oxidase Activity and Prevents Neurodegeneration and Memory Impairment in Rats With Chronic Cerebral HypoperfusionEnergy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease durationPaul EhrlichSponsorsBlue Cannatine One of my favorite tools for cognitive enhancement, especially after long plan rides, is Blue Cannatine. The delivery mechanism is unique (buccle troche). It is especially effective for me on improving short-term memory, focus, and verbal fluency.It’s the closest thing that I found to NZT and I think you guys should try it out. Get yours at troscriptions.com.Full disclosure: I am involved with the company (I like the product that much).BiOptimizers If you’re over 35, your enzyme levels have already begun to decline and your immune system can be more susceptible to viruses.Enzymes are the workhorses of digestion. They break your food down into usable macro and micronutrients. Research shows that by the time someone hits 65, their saliva and pancreatic secretions, both of which are involved in enzyme activity—can have declined by as much as 50%! This decline creates chronic indigestion, setting the stage for gut issues, yeast and mold overgrowth, even malnutrition. This is why I’m a big fan of enzyme and probiotic supplementation and one of the best companies I’ve ever found that specializes in optimizing your digestion through both of these supplements are my friends at BiOptimizers.Head on over to www.bioptimizers.com/boomer and use coupon code BOOMER to get 10% off any package. They have the best guarantee I’ve seen in the industry. It’s a 365 day FULL money back guarantee. If you want to try MassZymes, I strongly suggest you head on over to their site and grab it your free bottle before they either run out or just take down this offer. Head on over to https://masszymes.com/boomerfree and you’ll automatically get your free bottle added to your shopping cart.Disclaimer This information is being provided to you for educational and informational purposes only. This is being provided as a self-help tool to help you understand your genetics, biodata and other information to enhance your performance. It is not medical or psychological advice. Virtuosity LLC, or Decoding Superhuman, is not a doctor. Virtuosity LLC is not treating, preventing, healing, or diagnosing disease. This information is to be used at your own risk based on your own judgment. For the full Disclaimer, please go to (Decodingsuperhuman.com/disclaimer). See acast.com/privacy for privacy and opt-out information.
In episode 24 of the Primal Pioneer, we are diving into why you should dissolve these limiting beliefs and how you don't have to take on a deprivation attitude when it comes to these foods. Instead, you can have carbs and sugars within your diet without pathological impacts on your body. Some topics we touch on include: How a light environment plays a crucial role in how we process and digest carbohydrates. When your food is turned into energy, it's not detected just as fats, proteins, and carbohydrates. The food is also broken down into a more anatomical level involving protons and electrons. We look to diet to rectify metabolic disorders, however, diet is a band-aid approach to rectifying these issues. Cytochrome 1 (NAD NADH) needs UV light to function optimally. If you're someone who struggles with cravings of carbohydrates and sugars, or tries to stray away from these types of foods, I'm certain that after you tune in to episode 24, you will have the knowledge on how you can enjoy a healthy diet that still involves carbs and sugars. Be sure to tune in to episode 24 to learn more about how you can utilize health carbohydrates in your diet. If you have enjoyed this episode of the podcast, take a screenshot, share it in your Instagram stories and tag me, @sunlight_rx. CONNECT WITH HEATHAR: Website The Sunlight Rx EBook Instagram Facebook WORK WITH HEATHAR: For additional guidance utilizing the healing powers of sunlight to improve nutrient and hormonal health and production, check out my Sunlight Rx Ebook at my website, heatharshepard.com!
Join us on Patreon at http://patreon.com/MinuteEarth As we see a rise in misinformation on YouTube, educational channels like MinuteEarth need your support today more than ever. Thanks also to our YouTube members. ___________________________________________ To learn more, start your googling with these keywords: Misinformation: false information that is spread, regardless of intent to mislead Disinformation: deliberately misleading or biased information; manipulated narrative or facts ___________________________________________ Subscribe to MinuteEarth on YouTube: http://goo.gl/EpIDGd Support us on Patreon: https://goo.gl/ZVgLQZ And visit our website: https://www.minuteearth.com/ Say hello on Facebook: http://goo.gl/FpAvo6 And Twitter: http://goo.gl/Y1aWVC And download our videos on itunes: https://goo.gl/sfwS6n ___________________________________________ Credits (and Twitter handles): Video Writer, Director, and Narrator: Julián Gustavo Gómez (@thejuliangomez) Video Illustrator: Arcadi Garcia Rius (@garirius) With Contributions From: Henry Reich, Alex Reich, Kate Yoshida, Ever Salazar, Peter Reich, David Goldenberg, Sarah Berman Music by: Nathaniel Schroeder: http://www.soundcloud.com/drschroeder Image Credits: Emperor penguin photo by Cristopher Michel https://flic.kr/p/pKneEA Macaroni penguin photo by Liam Quinn https://flic.kr/p/9YG3s2 COX-2 graphics by Cytochrome c https://commons.wikimedia.org/wiki/File:Cyclooxygenase-2.png ___________________________________________ References: Anderson, Janna, and Lee Rainie. "The future of truth and misinformation online." Pew Research Center 19 (2017). “Why Is YouTube Broadcasting Climate Misinformation to Millions?” Avaaz, 16 Jan. 2020, http://secure.avaaz.org/campaign/en/youtube_climate_misinformation/. Del Vicario, Michela, et al. "The spreading of misinformation online." Proceedings of the National Academy of Sciences 113.3 (2016): 554-559.Iammarino, Nicholas K., and Thomas W. O’Rourke. "The challenge of alternative facts and the rise of misinformation in the digital age: Responsibilities and opportunities for health promotion and education." American journal of health education 49.4 (2018): 201-205. Lewis, Paul. "Fiction is outperforming reality”: How YouTube’s algorithm distorts truth." The Guardian 2 (2018): 2018. Meserole, Chris. "How misinformation spreads on social media—And what to do about it." The Brookings Institution (May 9, 2018), https://www.brookings. edu/blog/order-from-chaos/2018/05/09/how-misinformation-spreads-on-social-media-and-what-to-do-about-it (2018). O'Connor, Cailin. How Misinformation Spreads-and Why We Trust It. Scientific American, Sept. 2019, http://www.scientificamerican.com/article/how-misinformation-spreads-and-why-we-trust-it/. Roberts, David. YouTube Has a Big Climate Misinformation Problem It Can't Solve. Vox, 26 Jan. 2020, http://www.vox.com/energy-and-environment/2020/1/26/21068473/youtube-climate-change-misinformation-epistemic-crisis. Syed-Abdul, Shabbir, et al. "Misleading health-related information promoted through video-based social media: anorexia on YouTube." Journal of medical Internet research 15.2 (2013): e30.Williamson, Phil. "Take the time and effort to correct misinformation." Nature 540.7632 (2016): 171-171. Wood, Mike. “How Does Misinformation Spread Online?” Psychology Today, Sussex Publishers, 6 Dec. 2018, http://www.psychologytoday.com/us/blog/web-mistrust/201812/how-does-misinformation-spread-online. Educational creators featured in this video: Jordan Harrod – https://www.youtube.com/channel/UC1H1NWNTG2Xi3pt85ykVSHA SciShow – https://www.youtube.com/user/scishow Tom Scott – https://www.youtube.com/user/enyay ASAP Science – https://www.youtube.com/user/AsapSCIENCE ViHart – https://www.youtube.com/user/Vihart DrawCuriosity – https://www.youtube.com/channel/UCOs_jEnQF2ePJzjJTgRtunA TierZoo – https://www.youtube.com/channel/UCHsRtomD4twRf5WVHHk-cMw Wannabe Linguist – https://www.youtube.com/channel/UCkl3U62tqz-4SDxbqjn4G7A Kurzgesagt – https://www.youtube.com/user/Kurzgesagt Sabrina Cruz – https://www.youtube.com/user/NerdyAndQuirky msbeautyphile – https://www.youtube.com/user/msbeautyphile CGP Grey – https://www.youtube.com/user/CGPGrey Hot Mess – https://www.youtube.com/channel/UCsaEBhRsI6tmmz12fkSEYdw Jabrils – https://www.youtube.com/channel/UCQALLeQPoZdZC4JNUboVEUg CrashCourse – https://www.youtube.com/user/crashcourse Tippe Top Physics – https://www.youtube.com/user/tippetopphysics
Guidance Recap Podcast | In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Final Guidance - Podcast Transcript
Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Final Guidance - Podcast Transcript
“You know your body better than anyone. You’re living in it 24/7. No one should be dismissing the stuff you have to say.”-Em MillerEm and Kate Miller are the co-authors of chronic illness blog, TwoBeingHealthy.com and the YouTube channel of the same name. Forced into non-traditional careers by chronic illnesses that include Lupus, POTS, EDS, Mast Cell Activation disorder diagnosed in their late teens, their blog is a delightful mix of practical tips for patients, product testing, and their own struggles. Today they share their journey, tips on how to advocate for yourself as a patient, and the importance of community support.Visit:Blog: https://www.twobeinghealthy.com/YouTube channel: http://bit.ly/2TOvA7EDoctors Appointment – Our Top 10 Tips! : http://bit.ly/2sO6DxXInstagram: @twobeinghealthyTime Stamps:17:58 – Em’s diagnosis of Lupus at 1718:55 – Kate’s diagnosis and that people typically have more than one autoimmune disorder19:20 – POTS diagnosis19:28 – What is POTS20:20 – Difference between how Em and Kate experience their illnesses22:16 – What is EDS23:24 – Perceptions of chronic illness and breaking the stigma28:00 – Empowering aspect of the TwoBeingHealthy blog29:04 – Examples of what they share on their blog30:50 – Problem with doctors assuming patients with the same conditions will have the same traits31:30 – The importance of advocating for yourself at doctor’s appointments32:39 – The importance of not wearing makeup or nailpolish to doctors’ appointments 37:22 – The importance of tracking your symptoms and having notes of everything you want to cover during the appointment38:55- Knowing the tests to ask for re EDS and POTS + the problem with POTS43:13 – How to act with a new doctor and a time constraint44:04 – What to do if you feel you’re not being taken seriously by the doctor46:16 – The importance of finding a doctor you can trust49:20 – Problems communicating with doctors, especially renowned specialists52:32 – Cytochrome mutations and their effect on medication absorption53:54 – Difference between advocating for oneself and making demands55:54 – Importance of mutual respect in doctor patient relationships and finding a doctor you trust59:45 – On Em and Kate’s unsponsored product testing1:01:37 – The importance of personal comfort1:04:10 – The importance of finding what works for you 1:04:49 – Benefits of having an emergency relief kit1:06:47 – The Chronic Babe and being as well as possible1:07:27 – The big impact of little changes and recommendations1:08:10 – The importance of health and being proactive1:09:10 – What is Mast Cell Activation Disorder1:14:11 – The chronic illness community that developed around the blog1:17:45 – The challenge of balancing the difficult and raw with the positive and proactive1:19:50 – The benefit of having someone vs going it alone1:20:38 – The upside of following other people’s chronic illness journeys on social media1:21:52 – Importance of community, partnerships, and trust SHARE
We are solar powered beings! But we now spend 93% of our lives INDOORS. Brilliant founder of Sauna Space, Brian Richards, takes us through the fascinating body-wide healing phenomena of red light therapy. We cover all the science, the applications, and the specifics of how biologically relevant light (found largely in firelight, sunrise, and sunset) can cause massive changes in cell behavior, function, and repair. There are hundreds of research studies on this subject. Over 400 gold-standard, placebo-controlled clinical trials exist on this subject. It's only a matter of time before we see tanning salons and 7-Elevens popping up with this sort of therapy. Learn the facts now and become a savvy consumer on the good stuff. Our bodies are solar panels that need to be fueled by the light that nourishes them. If after this episode, you feel compelled to order a SaunaSpace product of your own, you can use promo code "AMRONMD" to receive a discount on your order.
Welcome to our 53rd Episode of the IntransikBeats Podcast, to prepare for the transition of the autumn days smoothly, we're glad to present to you an hour of the finest selection of dynamic paced techno variety mixed by 'Diane Cytochrome' from Lyon, France. With a classical music background at the conservatory, Diane became very passionate about electronic music culture and gave up the piano and her cello for turntables. In her artistic approach, she forms her universe by drawing inspiration from different trends to forge her intimate vision of music. The desired aesthetic: find the light in the dark, vector of hope like life after death, a world where the vibrations are contrasted through heavy, powerful and melodic sounds. The Techno influence essentially consolidates this dark universe contrasted by the light. A singular universe without complacency through its sound selection without boundaries. Diane opened 'Les Nuits Sonores 2013' in Lyon, by mixing at the inauguration of the Festival. The 2013/2014 season marks her professionalization in the performing field as a DJ, with her residency 'CYTOCHROME' at the Terminal Club in Lyon. A lot has happened for her since then and a lot of promising projects in Europe are to be announced soon, so make sure to check her links out down below to support as usual ;) In the meantime, we hope you enjoy this podcast as much as we do and we ll catch you next month, thank you for the great support ! Tracklisting: DVM - Cultural difference Falhaber - That One Night 90 Process - Alter Ego dynArec - Criticize - dynarec remix X - H - X - Come for U NTBR - ISLAND JKS - Inside Out AIROD - Shockwave planners FUERR - Khörög Zurag ILLINURSE - Ein Zwei Polizei Basswell - Intense Euphoria NTBR - PLAYA DE AJO Brain 6 - Observer Swedish sisters UVB remix Klamer - Lonely persecuted soul TRBL - Voluctris (NTBR Edit) Fresh Sounds https://soundcloud.com/dianecytochrome Follow her activity @ https://www.facebook.com/dianecytochrome/?ref=hl More Mixes @ https://www.mixcloud.com/hopdiane/
Nathan Adams investigates some of the most important molecular machines within our cells, the cytochrome p450 enzymes
Fri, 2 Dec 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/14644/ https://edoc.ub.uni-muenchen.de/14644/1/Scharfenberg_Michael.pdf Scharfenberg, Michael ddc:570, ddc:500, Fakultät für Biologie 0
Background: Resistance of Plasmodium falciparum to atovaquone in vitro and in vivo has been associated to mutations in the parasite cytochrome b gene. Methods: Cultures were sequentially subjected to increasing doses of atovaquone alone or in combination with cycloguanil and the cytochrome b gene was sequenced. Additionally, we investigated the parasite cytochrome b gene of a patient returning from Mali with Malarone(R) treatment failure in vivo. Results: All strains that survived atovaquone concentrations in vitro of 2 x 10(-8) to 2 x 10(7) M showed the M1331 mutation and one strain with the highest atovaquone concentration the additional mutation L171F. Sequencing of the in vivo treatment failure revealed a point mutation at codon 268 resulting in an amino acid change from tyrosine to serine. Based on the repeated emergence of mutations at codon 268, but no detection of alterations at codon 133 in vivo, we developed a detection method for the diagnostic of codon 268 polymorphisms as a potential atovaquone/proguanil resistance marker. A nested PCR with 3 different pairs of primers for the second round was designed. Each product was digested with restriction enzymes, capable to distinguish the wild type from the two reported mutations at codon 268. Conclusion: Mutations at codon 268 of the parasite cytochrome bc(1) gene are associated with atovaquone/proguanil treatment failure in vivo and can be used as potential resistance marker This method provides a novel and robust tool to investigate the relevance of codon 268 polymorphisms as resistance marker and to monitor the further emergence of atovaquone/proguanil resistance.
Cytochrome b2 contains 2-fold targeting information: an amino-terminal signal for targeting to the mitochondrial matrix, followed by a second cleavable sorting signal that functions in directing the precursor into the mitochondrial intermembrane space. The role of the second sorting sequence was analyzed by replacing one, two or all of the three positively charged amino acid residues which are present at the amino-terminal side of the hydrophobic core by uncharged residues or an acidic residue. With a number of these mutant precursor proteins, processing to the mature form was reduced or completely abolished and at the same time targeting to the matrix space occurred. The accumulation in the matrix depended on a high level of intramitochondrial ATP. At low levels of matrix ATP, the mutant proteins were sorted into the intermembrane space like the wild-type precursors. The results: (i) suggest the existence of one or more matrix components that specifically recognize the second sorting signal and thereby trigger the translocation into the intermembrane space; (ii) indicate that the mutant signals have reduced ability to interact with the recognition component(s) and then embark on the default pathway into the matrix by interacting with mitochondrial hsp70 in conjunction with matrix ATP; (iii) strongly argue against a mechanism by which the hydrophobic segment of the sorting sequence stops translocation in the hydrophobic phase of the inner membrane.
Cytochrome b2 reaches the intermembrane space of mitochondria by transport into the matrix followed by export across the inner membrane. While in the matrix, the protein interacts with hsp60, which arrests its folding prior to export. The bacterial-type export sequence in pre-cytochrome b2 functions by inhibiting the ATP-dependent release of the protein from hsp60. Release for export apparently requires, in addition to ATP, the interaction of the signal sequence with a component of the export machinery in the inner membrane. Export can occur before import is complete provided that a critical length of the polypeptide chain has been translocated into the matrix. Thus, hsp60 combines two activities: catalysis of folding of proteins destined for the matrix, and maintaining proteins in an unfolded state to facilitate their channeling between the machineries for import and export across the inner membrane. Antifolding signals such as the hydrophobic export sequence in cytochrome b2 may act as switches between these two activities.
Cytochrome c heme lyase (CCHL) catalyses the covalent attachment of the heme group to apocytochrome c during its import into mitochondria. The enzyme is membrane-associated and is located within the intermembrane space. The precursor of CCHL synthesized in vitro was efficiently translocated into isolated mitochondria from Neurospora crassa. The imported CCHL, like the native protein, was correctly localized to the intermembrane space, where it was membrane-bound. As with the majority of mitochondrial precursor proteins, CCHL uses the MOM19-GIP receptor complex in the outer membrane for import. In contrast to proteins taking the general import route, CCHL was imported independently of both ATP-hydrolysis and an electrochemical potential as external energy sources. CCHL which lacks a cleavable signal sequence apparently does not traverse the inner membrane to reach the intermembrane space; rather, it translocates through the outer membrane only. Thus, CCHL represents an example of a novel, 'non-conservative' import pathway into the intermembrane space, thereby also showing that the import apparatus in the outer membrane acts separately from the import machinery in the inner membrane.
The ubiquinol-cytochrome c reductase complex, like the other proton-pumping respiratory complexes of mitochondria, is an assembly of many different subunits. However, only a few of these subunits participate directly in the electron transfer and proton translocation. The roles of the other subunits are largely unknown. We discuss here some intriguing features of two of these subunits.
The biogenesis of cytochrome c1 involves a number of steps including: synthesis as a precursor with a bipartite signal sequence, transfer across the outer and inner mitochondrial membranes, removal of the first part of the presequence in the matrix, reexport to the outer surface of the inner membrane, covalent addition of heme, and removal of the remainder of the presequence. In this report we have focused on the steps of heme addition, catalyzed by cytochrome c1 heme lyase, and of proteolytic processing during cytochrome c1 import into mitochondria. Following translocation from the matrix side to the intermembrane-space side of the inner membrane, apocytochrome c1 forms a complex with cytochrome c1 heme lyase, and then holocytochrome c1 formation occurs. Holocytochrome c1 formation can also be observed in detergent-solubilized preparations of mitochondria, but only after apocytochrome c1 has first interacted with cytochrome c1 heme lyase to produce this complex. Heme linkage takes place on the intermembrane- space side of the inner mitochondrial membrane and is dependent on NADH plus a cytosolic cofactor that can be replaced by flavin nucleotides. NADH and FMN appear to be necessary for reduction of heme prior to its linkage to apocytochrome c1. The second proteolytic processing of cytochrome c1 does not take place unless the covalent linkage of heme to apocytochrome c1 precedes it. On the other hand, the cytochrome c1 heme lyase reaction itself does not require that processing of the cytochrome c1 precursor to intermediate size cytochrome c1 takes place first. In conclusion, cytochrome c1 heme lyase catalyzes an essential step in the import pathway of cytochrome c1, but it is not involved in the transmembrane movement of the precursor polypeptide. This is in contrast to the case for cytochrome c in which heme addition is coupled to its transport directly across the outer membrane into the intermembrane space.
The covalent attachment of heme to apocytochrome c, and therefore the import of cytochrome c into mitochondria, is dependent on both NADH plus a cytosolic cofactor that has been identified to be FMN or FAD. NADH in concert with flavin nucleotides mediates the reduction of heme. Heme in the reduced state is a prerequisite for its covalent attachment to apocytochrome c by the enzyme cytochrome c heme lyase and thus for subsequent translocation of cytochrome c across the outer mitochondrial membrane during import.
The import of cytochrome c into Neurospora crassa mitochondria was examined at distinct stages in vitro. The precursor protein, apocytochrome c, binds to mitochondria with high affinity and specificity but is not transported completely across the outer membrane in the absence of conversion to holocytochrome c. The bound apocytochrome c is accessible to externally added proteases but at the same time penetrates far enough through the outer membrane to interact with cytochrome c heme lyase. Formation of a complex in which apocytochrome c and cytochrome c heme lyase participate represents the rate-limiting step of cytochrome c import. Conversion from the bound state to holocytochrome c, on the other hand, occurs 10-30-fold faster. Association of apocytochrome c with cytochrome c heme lyase also takes place after solubilizing mitochondria with detergent. We conclude that the bound apocytochrome c, spanning the outer membrane, forms a complex with cytochrome c heme lyase from which it can react further to be converted to holocytochrome c and be translocated completely into the intermembrane space.
The nuclear cyt-2-1 mutant of Neurospora crassa is characterized by a gross deficiency of cytochrome c (Bertrand, H., and Collins, R. A. (1978) Mol. Gen. Genet. 166, 1-13). The mutant produces mRNA that can be translated into apocytochrome c in vitro. Apocytochrome c is also synthesized in vivo in cyt-2-1, but it is rapidly degraded and thus does not accumulate in the cytosol. Mitochondria from wild-type cells bind apocytochrome c made in vitro from either wild-type or cyt-2-1 mRNA and convert it to holocytochrome c. This conversion depends on the addition of heme by cytochrome c heme lyase and is coupled to translocation of cytochrome c into the intermembrane space. Mitochondria from the cyt-2-1 strain are deficient in the ability to bind apocytochrome c. They are also completely devoid of cytochrome c heme lyase activity. These defects explain the inability of the cyt-2-1 mutant to convert apocytochrome c to the holo form and to import it into mitochondria.
Molecular cloning and characterization of cytochrome c cDNA clones of Neurospora crassa wild-type (74A) and a cytochrome c-deficient mutant (cyc1-1) are described. Southern blot analysis of genomic DNA indicates that only one cytochrome c gene exists in the N. crassa genome. The cDNA sequence of the wild-type cytochrome c confirmed the previously determined protein sequence. Sequence analysis of the cyc1-1 cDNA for cytochrome c revealed the presence of a larger open reading frame, owing to the presence of an unspliced intron in the 3' end of the coding region. Splicing of this intron is obviously prevented due to the presence of two base exchanges in the highly conserved intron consensus sequences. Consequently, cyc1-1 synthesizes apocytochrome c with an altered carboxy terminus, 19 amino acids longer than the wild-type cytochrome c, with the final 27 amino acids being of an unrelated sequence. This alteration in the carboxy terminus renders the apocytochrome c incompetent for binding to mitochondria and, consequently, import into mitochondria. Thus, unlike other mitochondrial precursor proteins, where it has been demonstrated that the amino terminus alone is sufficient to target the protein to the mitochondria, an intact carboxy terminus is required for efficient import of apocytochrome c into mitochondria. This is independent confirmation for the view that the import pathway of cytochrome c is unique with respect to all other mitochondrial proteins studied to date.
The import of cytochrome c into mitochondria can be resolved into a number of discrete steps. Here we report on the covalent attachment of heme to apocytochrome c by the enzyme cytochrome c heme lyase in mitochondria from Neurospora crassa. A new method was developed to measure directly the linkage of heme to apocytochrome c. This method is independent of conformational changes in the protein accompanying heme attachment. Tryptic peptides of [35S]cysteine-labelled apocytochrome c, and of enzymatically formed holocytochrome c, were resolved by reverse-phase HPLC. The cysteine-containing peptide to which heme was attached eluted later than the corresponding peptide from apocytochrome c and could be quantified by counting 35S radioactivity as a measure of holocytochrome c formation. Using this procedure, the covalent attachment of heme to apocytochrome c, which is dependent on the enzyme cytochrome c heme lyase, could be measured. Activity required heme (as hemin) and could be reversibly inhibited by the analogue deuterohemin. Holocytochrome c formation was stimulated 5–10-fold by NADH > NADPH > glutathione and was independent of a potential across the inner mitochondrial membrane. NADH was not required for the binding of apocytochrome c to mitochondria and was not involved in the reduction of the cysteine thiols prior to heme attachment. Holocytochrome c formation was also dependent on a cytosolic factor that was necessary for the heme attaching step of cytochrome c import. The factor was a heat-stable, protease-insensitive, low-molecular-mass component of unknown function. Cytochrome c heme lyase appeared to be a soluble protein located in the mitochondrial intermembrane space and was distinct from the previously identified apocytochrome c binding protein having a similar location. A model is presented in which the covalent attachment of heme by cytochrome c heme lyase also plays an essential role in the import pathway of cytochrome c.
A microsomal cytochrome P-450-NADPH dependent enzyme which hydroxylates stereo- and regiospecifically carbon atom 14 of (S)- -N- methyltetrahydroprotoberberines has been discovered in a number of plant cell cultures originating from species containing protopine alkaloids; the monooxygenase was solubilized, partially purified (100-fold) and characterized.
The Fe/S protein of complex III is encoded by a nuclear gene, synthesized in the cytoplasm as a precursor with a 32 residue amino-terminal extension, and transported to the outer surface of the inner mitochondrial membrane. Our data suggest the following transport pathway. First, the precursor is translocated via translocation contact sites into the matrix. There, cleavage to an intermediate containing an eight residue extension occurs. The intermediate is then redirected across the inner membrane, processed to the mature subunit, and assembled into complex III. We suggest that the folding and membrane-translocation pathway in the endosymbiotic ancestor of mitochondria has been conserved during evolution of eukaryotic cells; transfer of the gene for Fe/S protein to the nucleus has led to addition of the presequence, which routes the precursor back to its “ancestral” assembly pathway.
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7423/1/7423.pdf Neupert, Walter; Köhler, Helmut; Hennig, Bernd ddc:610, Medizin
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7398/1/7398.pdf Neupert, Walter; Hennig, Bernd ddc:610, Medizin
The tertiary structures of horse, tuna, Neurospora crassa, horse [Hse65,Leu67]- and horse [Hse65,Leu74]-cytochromes c were studied with high-resolution 1H n.m.r. spectroscopy. The amino acid sequences of these proteins differ at position 46, which is occupied by phenylalanine in the horse proteins but by tyrosine in the remaining two, and at positions 67, 74 and 97, which are all occupied by tyrosine residues in horse and tuna cytochrome c but in the other proteins are substituted by phenylalanine or leucine, though there is only one such substitution per protein. The various aromatic-amino-acid substitutions do not seriously affect the protein structure.
H NMR resonance assignments in the spectra of horse, tuna, Neurmpora crassa and Candida krusei cyto-chromes c are described. Assignments have been made using NMR double-resonance techniques in conjunction with electron-exchange experiments, spectral comparison of related proteins, and consideration of the X-ray structure of tuna cytochrome c. Resonances arising from 11 residues of horse cytochrome c have been assigned.
Transport of apocytochrome c across the outer mitochondrial membrane and conversion to holocytochrome c were studied in vitro. Apocytochrome c was synthesized in a cell-free homogenate from Neurospora crassa. Transfer in vitro was accomplished in a reconstituted system consisting of the postribosomal supernatant of the cell-free homogenate and of isolated and purified mitochondria from Neurospora. The reconstituted system has the following characteristics: * 1. Apocytochrome c is rapidly cleared from the supernatant and holocytochrome c appears in the mitochondria with the same kinetics. More than 80% of the apocytochrome c employed is converted to holocytochrome c. No transient accumulation of apocytochrome c is found in mitochondria. * 2. The heme group becomes covalently linked to apocytochrome c in the reconstituted system as demonstrated by analysis of tryptic peptide maps of the apoprotein and holoprotein. * 3. Deuterohemin added to the reconstituted system but not deuteroporphyrin inhibits the formation of holocytochrome c. This inhibition is reversed by protohemin. * 4. In the presence of deuterohemin about half of the apocytochrome c remains in the supernatant; the other half becomes associated with the mitochondria. The latter portion is tightly bound and is specifically released upon incubation of the mitochondria with excess apocytochrome c. It is converted to holocytochrome c after addition of protohemin. We conclude from these observations that apocytochrome c is transported across the outer mitochondrial membrane via receptor sites. In the presence of the heme analogue deuterohemin, binding to the receptor sites on the cytoplasmic surface of the outer mitochondrial membrane still takes place but translocation does not. The latter step is apparently coupled to the covalent linkage of the heme group. We suggest that the formation of the thioether bonds between apoprotein and heme is catalysed by an enzyme in the intermembrane space and that deuterohemin can compete with protohemin for binding to the enzyme. Finally, the data indicate that it is the heme group and not the porphyrin group which is coupled to the apoprotein.
The majority of mitochondrial proteins are synthesized on cytoplasmic ribosomes and transferred to the mitochondria where they are assembled to supramolecular structures. The intracellular transfer of these proteins appears to occur by a post-translational mechanism, i.e., it involves extramitochondrial precursor forms which are translocated in a step independent from translation. The synthesis and transfer of individual proteins was investigated in vivo, or in vitro employing homologous and heterologous cell free systems for protein synthesis. Cytochrome c was initially made as the apoprotein. This precursor protein was converted to the holoprotein on uptake by mitochondria in reconstituted systems. Integrity of mitochondria was essential for the apo to holo conversion. In the case of the ADP/ATP carrier protein, an integral transmembrane protein of the inner mitochondrial membrane, the initial translation product had the same apparent molecular weight as the mature protein. It was found in soluble form in the post-ribosomal supernatant. Citrate synthase, a matrix protein, was synthesized as a precursor with an apparent molecular weight of 47 000. Transfer to the mitochondria was accompanied by cleavage to yield a molecular weight of 45 000. The significance of these results in relation to the mechanisms of intracellular transfer and of assembly of the individual proteins is discussed.
Sat, 1 Dec 1979 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7339/1/Neupert_Walter_7339.pdf Neupert, Walter; Paluch, Ulrich; Zimmermann, Richard ddc:610, Medizin
# 1. Precipitating antibodies specific for apocytochrome c and holocytochrome c, respectively, were employed to study synthesis and intracellular transport of cytochrome c in Neurospora in vitro. # 2. Apocytochrome c as well as holocytochrome c were found to be synthesized in a cell-free homogenate. A precursor product relationship between the two components is suggested by kinetic experiments. # 3. Apocytochrome c synthesized in vitro was found in the post-ribosomal fraction and not in the mitochondrial fraction, whereas holocytochrome c synthesized in vitro was mainly detected in the mitochondrial fraction. A precursor product relationship between postribosomal apocytochrome c and mitochondrial holocytochrome c is indicated by the labelling data. In the microsomal fraction both apocytochrome c and holocytochrome c were found in low amounts. Their labelling kinetics do not suggest a precursor role of microsomal apocytochrome c or holocytochrome c. # 4. Formation of holocytochrome c from apocytochrome c was observed when postribosomal supernatant containing apocytochrome c synthesized in vitro was incubated with isolated mitochondria, but not when incubated in the absence of mitochondria. The cytochrome c formed under these conditions was detected in the mitochondria. # 5. Conversion of labelled apocytochrome c synthesized in vitro to holocytochrome c during incubation of a postribosomal supernatant with isolated mitochondria was inhibited when excess isolated apocytochrome c, but not when holocytochrome c was added. # 6. The data presented are interpreted to show that apocytochrome c is synthesized on cytoplasmic ribosomes and released into the supernatant. It is suggested that apocytochrome c migrates to the inner mitochondrial membrane, where the heme group is covalently linked to the apoprotein. The hypothesis is put forward that the concomitant change in conformation leads to trapping of holocytochrome c in the membrane. The probles of permeability of the outer mitochondrial membrane to apocytochrome c and the site and nature of the reaction by which the heme group is linked to the apoprotein are discussed.
Tue, 15 Oct 1974 12:00:00 +0100 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T36-447P02V-2S&_user=616146&_coverDate=10%2F15%2F1974&_rdoc=22&_fmt=high&_orig=browse&_srch=doc-info(%23toc%234938%231974%23999529997%23268635%23FLP%23display%23Volume)&_cdi=4938&_sort=d&_docancho https://epub.ub.uni-muenchen.de/7275/1/Neupert_Walter_7275.pdf Neupert, Walter; Werner, Sigurd; Rücker, Axel von
Three different cell types of Neurospora crassa deficient in cytochrome oxidase were studied: the nuclear mutant cni-1, the cytoplasmic mutant mi-1 and copper-depleted wild-type cells. * 1. The enzyme-deficient cells have retained a functioning mitochondrial protein synthesis. It accounted for 12–16% of the total protein synthesis of the cell. However, the analysis of mitochondrial translation products by gel electrophoresis revealed that different amounts of individual membrane proteins were synthesized. Especially mutant cni-1 produced large amounts of a small molecular weight translation product, which is barely detectable in wild-type. * 2. Mitochondrial preparations of cytochrome-oxidase-deficient cells were examined for precursors of cytochrome oxidase. The presence of polypeptide components of cytochrome oxidase in the mitochondria was established with specific antibodies. On the other hand, no significant amounts of heme a could be extracted. * 3. Radioactively labelled components of cytochrome oxidase were isolated by immunoprecipitation and analysed by gel electrophoresis. All three cell types contained the enzyme components 4–7, which are translated on cytoplasmic ribosomes. The mitochondrially synthesized components 1–3 were present in mi-1 mutant and in copper-depleted wild-type cells. In contrast, components 2 and 3 were not detectable in the nuclear mutant cni-1. Both relative and absolute amounts of these polypeptides in the enzyme-deficient cells were quite different from those in wild-type cells. * 4. The components of cytochrome oxidase found in the enzyme-deficient cells were tightly associated with the mitochondrial membranes. * 5. Processes, which affect and may control the production of enzyme precursors or their assembly to a functional cytochrome oxidase are discussed.