Cytochromes Puns

Just curious what has worked for you?

All the online materials talk about atleast cytochrome B, but it’s basically just an intermediate step to passing electrons to Cytochrome C

My Kaplan Book doesn’t even acknowledge the existence of Cytochrome B or C1.

Are they not tested on the MCAT?

Regulation of lipids is central to replicative senescence - Molecular BioSystems (RSC Publishing)

Free fatty acids, insulin resistance, and type 2 diabetes mellitus - PubMed (nih.gov)

With a layman's understanding of physiology, I have found it convincing that the BCL-xl inhibitors will allow for the release of cytochrome oxidases from the mitochondria which causes targetted apoptosis.

Free Fatty Acids naturally cause an inhibition of cytochrome oxidases and block cytochrome oxidase-reliant respiration. Elevated FFAs are also central to Diabetes and metabolic syndrome. There are few metabolites which are not able to be disposed of by the body. However, the unstable Poly-unsaturated fats in certain conditions produce metabolites such as lipofuscin which have only one pathway but to be stored in soft tissue. Some of these metabolites are stored in cells and accumulate with age leading to senescent activity (see first article above.) Diabetes makes this process much worse (see second article.)

Essentially, UBX1325 is dealing with this issue, exacerbated by diabetes, which causes cells to be suspended in a low-functional, anti-apoptosis state. There is no fixing these cells and there is no ability for the body to regulate them because they pathologically block the cytochrome oxidase activity required to remove them. Because UBX1325 inhibits BCL-xl it restores this cytochrome oxidase activity to help the body do what it does naturally.

UBX is on to something.

tl;dr Diabetes is associated with elevated free fatty acids, free fatty acids are responsible for senescence by blocking cytochrome oxidase and protected through BCL-xl. UBX1325 blocks BCL-xl to let the body destroy these cells damaged by FFAs, through cytochrome oxidase pathway of apoptosis.

With Bacopa, the usual fear is that, by inhibiting cytochrome P450, it can prevent the metabolization and thus the elimination of certain antidepressants and anti-psychotics, leading to a potential overdose. [1] [2]

[1] See: "Bacopa Side Effects" https://www.superfoods-scientific-research.com/medicinal-herbs/bacopa-side-effects.html

[2] PUBMED: Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents https://pubmed.ncbi.nlm.nih.gov/24566323/

However, I found nothing regarding bacopa and xanax (generic name: alprazolam) despite looking for articles or threads on the subject via numerous search engines (Google, DuckDuckGo, etc.). However, it is my personal experience that bacopa prevents xanax from working at all (which I take on rare ocassions for chest pains and panic attacks).

Alprazolam (xanax) is metabolized by Cytochrome P450 into alpha-hydroxy alprazolam (alpha-OHALP, pharmacologically more active) and 4-hydroxy alprazolam (4-OHALP, pharmacologically less active). [2]

[2] https://pubmed.ncbi.nlm.nih.gov/12196913/

I've been taking Bacopa for a few days now, and I just tried taking 0.5mg of xanax for an acute case of anxiety, and I felt nothing. Took a second 0.5mg of xanax an hour later. Still felt NOTHING.

So I suppose I'll need to discontinue Bacopa despite its blood flow improving and neuroprotective effects against the type of damage benzodiazipines can do to the brain. Luckily, I take other neuroprotective supplements (like Gingko Biloba and Acetyl-L-Carnitine) that do not interfere with Cytochrome P450 activity.

So, just a warning: if you are prescribed xanaz (i.e. alprazolam, or any other type of benzodiazipine for that matter) for panic attacks or for chest pains (angina) resulting from hypoxia (lack of blood flow to the heart, which can be induced by extreme stress or anxiety), you likely want to avoid taking Bacopa as it will interfere with your metabolization of the drug. It may still work to some degree, I don't know, perhaps in a few hours I'll feel it kick in. I'll report back later with any changes.

But yes, two hours later, and I can't feel it and my anxiety is still here an hour later and my chest pains had to be subdued with nitroglycerin. So, yes, if you take any other prescription drug that

Uworld says metronidazole is a substrate, FA says it's an inhibitor. Where is truth?

Introduction
Hello fellow drug nerds.

I have been enjoying the content of this forum for a while and decided to contribute with some of my own research. Below is what I have compiled so far.

If you have any additional or corrective knowledge about these processes, feel free to join in and help create an accurate understanding of how the enzyme inhibition works and practical pointers to safe use.

The Grapefruit Effect
Grapefruits contain the compounds furanocoumarins, which inhibits the CYP3A4 enzyme, which improve the availability of dissociatives, stimulants, sedatives and many other recreational and non-recreational compounds.

The furanocoumarins are supposedly found in the greatest concentration in the juice of the grapefruit, but final confirmation to this fact is needed.

The lower the bioavailability of any given drug, the higher the increase of the drug will be. The inhibition of the CYP3A4 enzyme leads to a higher systemic concentration (more drug actively available to create effect in body) as the chemical processes that usually break it down, become considerably slowed by the lack of enzymes.

This effectively allows users of the grapefruit effect to lower their doses of certain substances, as potency will be increased. The effect will, however differ, as the general activity of the CYP3A4 enzyme varies broadly in people (up to a 40-fold difference). Which explains the various reactions seen. It is therefore advisable to proceed with caution and stay attentive to past and present patterns in personal metabolism.

To inhibit the CYP3A4 enzyme, a 200 g of grapefruit should suffice to create a "clinically relevant" inhibitory effect and it does not matter if the grapefruit is white or red (although common misconceptions suggests otherwise).

The inhibition of the CYP3A4 enzyme occurs in the intestine, but not the liver, which seem to suggest that it specifically applies to the oral dosing route. If you have knowledge to suggest that the effect also takes place in the liver at a certain concentration, feel free to chime in.

https://preview.redd.it/ypy44qtf5be71.png?width=640&format=png&auto=webp&s=27d12e12f700a7c0e99c41c2f7753b9bf47fbe24

As the one who have severe drug-metabolism malfunction, I found some information might related with our symptoms. I'm not sure I'm allowed to post link, so let me know if this is not allowed. Also, I'm not good at English, if i misunderstand any report, please let me know.

https://dmd.aspetjournals.org/content/24/10/1134.short

" Ciprofloxacin and norfloxacin significantly depressed the N-demethylation of erythromycin by CYP3A4 in human microsomes and by CYP3A2 in rat microsomes." " These studies in hepatic microsomes demonstrate that fluoroquinolones can decrease CYP3A- and CYP1A-mediated biotransformation by competitive inhibition and that they have the potential to cause drug interactions with agents metabolized by these enzymes."

This report said FQ antibiotics inhibit cytochrome P450 enzymes which used as drug metabolizer. Cytochrome p450 is an important enzyme in relation to drug liver metabolism and drug interaction. There are many active differences in this enzymes between races and individuals, resulting in differences in the function of drug metabolism, which can cause different drug effects for each person. While others can tolerate it well, and some have side effects from it. Major CYP450 enzymes involved in drug metabolism (CYP1A2, CYP2B6, CYP2C9 and CYP3A4) can be affected by FQ antibiotics, and this might be the reason why some floxie fellows such as me can't tolerate medicine.

https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers

This are list of Inhibitor and Inducer of Cytochrome P450 enzymes. FQ antibiotics are on the list of CYP1A2, CYP2B6, CYP2C9 and CYP3A4 Inhibitors. Especially Ciprofloxacin and Norfloxacin, unluckily. I think FQ antibiotics inhibit our Cytochrome P450 enzymes with wrong way, then it affects our drug metabolism. That's why we cannot tolerate some supplements, or medicine such and flagyl, NSAIDs, Steroids, Antifungals, etc etc. It's side effects can be severe joint pain, tingling feeling all over the body, anxiety, acid reflux etc etc.

The key point is, our body's drug metabolism enzymes hurted by FQ, cannot metabolize medication through the liver well, so the residual toxicity from the medicine is remaining and floating in our blood, which i

Today’s fact of the day will address kava’s ability to inhibit (reduce function) of various enzymes known as cytochromes.

Cytochrome P450, also known as CYPs, are a family of enzymes that oxidize (break down) about 75-80% of all drugs in the body. These are important in the world of kava because kava, kava extract, and individual kavalactones have been shown in several studies to inhibit these enzymes to different degrees. When these enzymes are inhibited, whatever chemical which used that enzyme to metabolize will be slowed in its elimination, or at least in theory based on these papers.

https://preview.redd.it/fnj2pidvcdr61.jpg?width=2200&format=pjpg&auto=webp&s=12d7be6286a141120a6ba0b5f97866e3b3034d60

Most of the work today resides in the image attached. Attached is my attempt at taking these three studies and producing their results in a readable format. We’re using what’s known as IC50 values to denote the strength of inhibition of kava and fractions of kava. IC50 is defined as: a measure of the potency of a substance in inhibiting a specific biological or biochemical function [7]. Quite a number of natural products can inhibit these enzymes including grapefruit juice. In the attached diagram we see the reference values for grapefruit highlighted in yellow. These are the inhibition values you would see if you consumed grapefruit juice instead of kava. It’s worth it to note the inhibition values of grapefruit are much stronger than those of kava. The main two enzymes used in the vast bulk of elimination of pharmaceutical drugs are the enzymes CYP2D6 and CYP3A4. CYP2D6 was thought to be inhibited by kava, however these studies provide evidence that shows this may not be the case. CYP3A4, which accounts for roughly half of all drug metabolism has indeed shown inhibition in the presence of kava, and kava fractions.

What this means to the average kava drinker is that if you consume kava daily, you may want to watch out for pharmaceutical drugs which caution against the concurrent consumption of grapefruit juice. This warning is almost always printed on the side of the bottle. While kava may not be as strong of an inhibitor at these sites, it stands to reason that the compounding effect of consuming kava daily may indeed cause these inhibitory effects. This can cause these specific drugs to stay in your system for longer periods than intended, or cause their metabolites to stay in a specific form for a longer amount of time. Either

ADMET prediction of my query compounds show one of them isn’t a substrate or inhibitor of CYP2D6, 3A4, 1A2, 2C19, 2C9, but one of them is both a substrate and inhibitor of all except CypD6 . How do I discuss this please.

Cytochrome P450 CxnD exhibited C−S bond forming activity in chuangxinmycin biosynthesis, generating the unique tricyclic indole-S-hetero scaffold from thiol intermediates. Structural characterization of CxnD with a substrate analogue proposed a radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate.

Abstract

Microbial sulfur-containing secondary metabolites show various biological activities, but the C−S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C−S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp2)−H thiolation by the P450 in chuangxinmycin biosynthesis.

https://ift.tt/2QPtCo0

I take Strattera 25mg, Wellbutrin 150mg & Brintellix 10mg daily.
(I suffer from dysthymic & anxiety disorder, OCPD, ADD and severe misophonia)

My doctor prescribes me this combination of drugs, but it seems a strange combination to me, considering many cytochrome 450 interactions.

Anyway, I recently changed the intake of vortioxetine from morning to just before bedtime. So before: I took all three pills together in the morning / After: Bupropion and Atomoxetine in the morning, Vortioxetine in the evening.

The mood changes that followed the days after this change lead me to suspect that there is a substantial difference in the resulting plasma concentrations of vortioxetine and its metabolites, after having changed the timing of intake.

So these are my questions:

• Could this be possible?

• Is it therefore advisable not to take drugs with a large P450 interaction together, but better spread as far apart as possible throughout the day?

• Is it even possible to obtain stable plasma concentrations when there are so many P450 interactions between the different drugs?

• Are there any studies about this subject?

• Has anyone already used this combination with his patients? (with good results?)

Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c02146

Marc Garcia-Borràs, S. B. Jennifer Kan, Russell D. Lewis, Allison Tang, Gonzalo Jimenez-Osés, Frances H. Arnold, and K. N. Houk

https://ift.tt/3eI59sO

url: https://www.sciencedirect.com/science/article/abs/pii/S1055790398905383?via%3Dihub

DOI: 10.1006/mpev.1998.0538

PMID: 10082619

Thank you in advance!

Has ANYONE read this article?? Link: https://pubs.acs.org/doi/10.1021/acs.biochem.7b00890

I cannot wrap my brain around it and would be beyond grateful if someone who actually understands this research would take the time to simplify for me what the heck is going on here.

Microbial sulfur‐containing secondary metabolites show various biological activities and the C‐S bond‐forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C‐S bond forming activity in S‐heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole‐fused dihydrothiopyran skeleton from a L‐Trp‐derived thiol intermediate. Furthermore, X‐ray crystal structure of CxnD in complex with a substrate analogue and structure‐based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra‐molecular C(sp2)‐H thiolation by the P450 in chuangxinmycin biosynthesis.

https://ift.tt/2QPtCo0