Vitamin B 12 is a complex organometallic cofactor associated with three subfamilies of enzymes: adenosylcobalamin-dependent isomerases, methylcobalamin-dependent methyltransferases, and dehalogenases. These enzymes exploit different chemical aspects of the cofactor during catalysis. Glutamate mutase is one of a group of adenosylcobalamin-dependent enzymes that catalyze unusual isomerizations that proceed through the formation of radical intermediates. It shares a structurally similar cobalamin-binding domain with methylcobalamin-dependent enzymes. Adenosylcobalamin (coenzyme B 12) serves as the cofactor for a group of enzymes that catalyze unusual rearrangement or elimination reactions.
The use of radical intermediates in an active site lined with amino acid side chains that threaten to extinguish the reaction by presenting alternative groups for abstraction poses the conundrum. Adenolsylcobalamin-dependent enzymes catalyze free radical mediated reactions of their substrates. Stereochemical methods have been used to establish the nature of the cofactor.
B 12-dependent enzymes found in mammals are adenosylcobalamin-dependent methylmalonyl-CoA mutase and methylcobalamin-dependent methionine synthase. Methylmalonyl-CoA mutase catalyzes the rearrangement of methylmalonyl-CoA to form succinyl-CoA, an important reaction in the breakdown of fatty acids with an odd number of. Adenosylcobalamin (AdoCbl) is an essential vitamin whose production is limited to bacterial fermentation.
In this study, an alternative method for the synthesis of AdoCbl was reported. Glutamate mutase is one of a group of adenosylcobalamin-dependent enzymes that catalyze unusual isomerizations that proceed through the formation of radical intermediates. Enzymes that require adenosylcobalamin for activity catalyze reactions in which the first step is homolytic cleavage of adenosylcobalamin to form cob(II)alamin.
| Article | Description | Site |
|---|---|---|
| Effect on coenzyme binding and catalysis of mutations in the … | Glutamate mutase is one of a group of adenosylcobalamin-dependent enzymes that catalyze unusual isomerizations that proceed through the formation of a radical. | tcu.elsevierpure.com |
| Identification of a Reactivating Factor for Adenosylcobalamin … | Our findings indicate that the inactivated holoenzyme undergoes rapid and continuous reactivation in the presence of ATP, Mg2+, and free adenosylcobalamin in permeabilized… | www.ncbi.nlm.nih.gov |
| How Enzymes Control the Reactivity of Adenosylcobalamin | The objective of this study is to examine the manner in which enzymes regulate the reactivity of adenosylcobalamin, with a particular focus on its impact on coenzyme binding and the catalysis of mutations in the conserved histidine-aspartate pair. | ouci.dntb.gov.ua |
📹 Cofactors and Reactive Moieties of Vitamin B12 (Methylcobalamin, Adenosylcobalamin, Cob(III)alamin)
Vitamin B12, also known as cobalamin, is a crucial nutrient with various cofactor and reactive moiety forms. Cofactor Forms: 1.
What interrupts B12 absorption?
Digestive diseases: Diseases that affect the digestive system, like Crohn’s disease and celiac disease, can prevent your body from fully absorbing vitamin B12. Surgery: People who have gastrointestinal surgery — like a gastric bypass (weight loss surgery) — can have difficulty absorbing vitamin B12.
What is vitamin B12 deficiency?. Vitamin B12 deficiency happens when your body is either not getting enough or not absorbing enough vitamin B12 from the food that you eat that it needs to function properly. Vitamin B12 is an important nutrient that helps your body make red blood cells and DNA, the genetic material in all of your cells.
Untreated, vitamin B12 deficiency can cause physical, neurological and psychological problems.
What is vitamin B12?. Vitamin B12 is an important nutrient that helps your body keep your nerve cells and blood cells healthy. It also helps your body make DNA, the genetic material in all of your cells. Your body doesn’t make vitamin B12 on its own. You have to consume food and drinks that have vitamin B12 in order to get it. Vitamin B12 is found in animal products you eat and drink, like meat, dairy and eggs. It can also be found in fortified foods (foods that have certain vitamins and nutrients added to them) such as certain cereals, bread and nutritional yeast.
What enzyme metabolizes B12?
Abstract. Vitamin B12, the “antipernicious anaemia factor”, is a crystallisable cobalt-complex, which belongs to a group of unique “complete” corrinoids, named cobalamins (Cbl). In humans, instead of the “vitamin”, two organometallic B12-forms are coenzymes in two metabolically important enzymes: Methyl-cobalamin, the cofactor of methionine synthase, and coenzyme B12 (adenosyl-cobalamin), the cofactor of methylmalonyl-CoA mutase. The cytoplasmatic methionine synthase catalyzes the transfer of a methyl group from N-methyl-tetrahydrofolate to homocysteine to yield methionine and to liberate tetrahydrofolate. In the mitochondrial methylmalonyl-CoA mutase a radical process transforms methylmalonyl-CoA (a remains e. g. from uneven numbered fatty acids) into succinyl-CoA, for further metabolic use. In addition, in the human mitochondria an adenosyl-transferase incorporates the organometallic group of coenzyme B12. In all these enzymes, the bound B12-derivatives engage (or are formed) in exceptional organometallic enzymatic reactions. This chapter recapitulates the physiological chemistry of vitamin B12, relevant in the context of the metabolic transformation of B12-derivatives into the relevant coenzyme forms and their use in B12-dependent enzymes.
Vitamin B12-derivatives-enzyme cofactors and ligands of proteins and nucleic acids.
Gruber K, Puffer B, Kräutler B. Gruber K, et al. Chem Soc Rev. 2011 Aug;40:4346-63. doi: 10. 1039/c1cs15118e. Epub 2011 Jun 20. Chem Soc Rev. 2011. PMID: 21687905 Review.
What is the enzymatic role of cobalt in vitamin B12?
Cobalt, a trace element, is crucial for rumen microorganisms in the formation of vitamin B12. Vitamin B12 is essential in the metabolism of mammals and is involved in multiple metabolic reactions, such as the metabolism of carbohydrates, lipids, amino acids, and DNA. Adenosylcobalamin and methylcobalamin are coenzymes of methylmalonyl coenzyme A (CoA) mutase and methionine synthetase, which are essential for energy through ruminal metabolism. Cobalt deficiency can lead to hyporexia, reduced growth and weight loss, liver steatosis, anemia, impaired immune function, impaired reproductive function, and even death. Cobalt status in ruminant animals can be assessed through direct measurement of blood or tissue concentrations of cobalt or vitamin B12, as well as the level of methylmalonic acid, homocysteine, or transcobalamin in blood, urine, and other variables. Current recommendations suggest increasing cobalt supplementation and placing it around 0. 20 mg Co/kg DM. While there is no consensus on the response to increased supplementation with cobalt, studies have shown that when the total Co of the diet is approximately 1 to 1. 3 ppm (mg/kg), maximum responses are observed in milk production.
What limits B12 absorption?
Gastric acid inhibitors. People take gastric acid inhibitors to treat certain digestion problems, such as gastroesophageal reflux disease and peptic ulcer disease. These drugs can interfere with vitamin B12 absorption from food by slowing the release of hydrochloric acid into the stomach, leading to vitamin B12 deficiency. Gastric acid inhibitors include omeprazole (Prilosec), lansoprazole (Prevacid), cimetidine (Tagamet), and ranitidine (Zantac).
Metformin. Metformin is used to treat prediabetes and diabetes. Metformin might reduce vitamin B12 absorption and lower blood levels of vitamin B12.
Tell your doctor, pharmacist, and other health care providers about any dietary supplements and prescription or over-the-counter medicines you take. They can tell you if the dietary supplements might interact with your medicines. They can also explain whether the medicines you take might interfere with how your body absorbs or uses other nutrients.
Which enzyme helps in absorption of vitamin B12?
Absorption. The absorption of vitamin B 12 in humans is complex( 1, 2 ). Vitamin B 12 in food is bound to proteins and isreleased from the proteins by the action of a high concentration of hydrochloricacid present in the stomach. This process results in the free form of thevitamin, which is immediately bound to a mixture of glycoproteins secreted bythe stomach and salivary glands. These glycoproteins, called R-binders (orhaptocorrins), protect vitamin B 12 from chemical denaturation in thestomach. The stomach’s parietal cells, which secrete hydrochloric acid, also secrete a glycoprotein called intrinsic factor. Intrinsic factor bindsvitamin B 12 and ultimately enables its active absorption. Althoughthe formation of the vitamin B 12 – intrinsic factor complex wasinitially thought to happen in the stomach, it is now clear that this is not thecase. At an acidic pH the affinity of the intrinsic factor for vitaminB 12 is low whereas its affinity for the R-binders is high. When thecontents of the stomach enter the duodenum, the R-binders become partly digestedby the pancreatic proteases, which causes them to release their vitaminB 12. Because the pH in the duodenum is more neutral than that in thestomach, the intrinsic factor has a high binding affinity to vitaminB 12, and it quickly binds the vitamin as it is released from theR-binders. The vitamin B 12 -intrinsic factor complex then proceeds tothe lower end of the small intestine, where it is absorbed by phagocytosis byspecific ileal receptors ( 1, 2 ).
Populations at risk for andconsequences of vitamin B 12 deficiency. Vegetarians.
Because plants do not synthesise vitamin B 12, individuals who consume diets completely free of animal products (vegan diets)are at risk of vitamin B 12 deficiency. This is not true oflacto-ovo-vegetarians, who consume the vitamin in eggs, milk, and other dairyproducts.
Is adenosylcobalamin a coenzyme?
Adenosylcobalamin participates as a cofactor in radical-mediated 1, 2-carbon skeleton rearrangements. These processes require the formation of the deoxyadenosyl radical through homolytic dissociation of the carbon-cobalt bond. This bond is exceptionally weak, with a bond dissociation energy of 31 kcal/mol, which is further lowered in the chemical environment of an enzyme active site. An enzyme that uses adenosylcobalamin as a cofactor is methylmalonyl-CoA mutase (MCM).
Further experimentation has also determined adenosylcobalamin’s role in regulating expression of some bacterial genes. By binding to CarH, ( clarification needed ) AdoCbl can modulate carotenoid genes, which confer warm colors onto various plants. Carotenoid transcription is activated by sunlight, due to the response from AdoCbl. There are other photoreceptors across different bacterial communities, aside from CarH, that also have reactive capability when bound to AdoCbl. For instance, AerR is another factor that uses AdoCbl to give off purple pigmentation. Additional examination of adenosylcobalamin-bound enzymes and the development of this cofactor over time may prove to hold regulatory function of DNA and RNA.
- Methylcobalamin
- Hydroxocobalamin
- Cyanocobalamin
- Vitamin B12
- Cobalamin biosynthesis
- Nitric oxide
How does adenosylcobalamin work?
Adenosylcobalamin, another cofactor form of vitamin B12, is essential for the conversion of methylmalonyl coenzyme A (a coenzyme A–linked form of methylmalonic acid (MMA)) to succinyl coenzyme A by MUT. This is an important step in the extraction of energy from protein and fat in the mitochondrial citric acid cycle.
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What types of reactions are catalyzed by enzymes?
Primary Enzyme Classifications. Recall from Chapter 6 that there are six major classes of biochemical reactions that are mediated by enzymes (Table 7. 1). These include oxidation-reduction reactions, group transfer reactions, hydrolysis reactions, the formation/removal of carbon-carbon double bonds, isomerization reactions, and ligation reactions. This section will give you a brief introduction to these six types of reactions.
Table 7. 1 Primary Enzyme Classification System by the Enzyme Commission (EC)
An oxidation-reduction (redox) reaction is a type of chemical reaction that involves a transfer of electrons between two atoms or compounds. The substance that loses the electrons is said to be oxidized, while the substance that gains the electrons is said to be reduced. Redox reactions always have to occur together. If one molecule is oxidized, then another molecule has to be reduced (ie. electrons don’t appear out of thin air to be added to a compound, they always have to come from somewhere!).
What is the biosynthesis of adenosylcobalamin?
The biosynthesis of adenosylcobalamin starts with the biosynthesis of the tetrapyrrole intermediate uroporphyrinogen-III, which is a common intermediate in the biosynthesis of several important compounds, such as heme and chlorophyl.
📹 The BEST & WORST Forms of Vitamin B12
Vitamin B12 is incredibly important and many people simply don’t get enough. And if you don’t get enough then you’ll end up with …
With hydroxocobalamin injection I was only better for 4 months, after I started methylcobalamin injections 1000mcg I got better again. I tried to also add hydroxocobalamin again but immediately symptoms came back. Now 5 years on methylcobalamin and also added adenosyl in one shot.. But still experience low Thyroid symptoms. Cut out gluten and dairy. But find it difficult to find T2 that ships to the Netherlands. Trying carnivore, but I somehow crash every time I eliminate carbs. Thanks for the outline, first time ever I saw somebody explain it thoroughly! You’re good!
My friend is in ICU for the third time in 3 months with the help of cyanocobalamin. Instead of giving her the other B12, they actually raised her dose of the cyanide version. 4 hospitals in 4 months, 2 helicopter rides, intubated several times and discharged into a facility to continue her toxic regimen, allow her to go without O2, breathing treatments, while delaying therapy due to unorganization, lack of staff, etc. I could go on and on. No one believes me or will even entertain the idea. I can’t even breath I’m so upset. 😢
It’s so worth it to listen again. But your right they’re mega info. We are what we digest for sure. Unless you have an ulcer start making sure you have great digestion. For years now I drink ACV a teaspoon in water always mix. Even add lemon. This alone helps so much and works for so many. Look into this. Energy will improve and for most great for help prevent with gallstones. Anyway saying all this. I take liquid organic usually cherry flavored Methocabolamin B12. That’s just me. Have a great day and there’s amazing info on utube as you all ready know. Dr Childs is so informative. Go slow and just start as know dought your doing now. 😊Have a great day.
This is the FIRST time ever I hear about cyanocobalamin being pretty much, poisonous. I have just purchased 360 more pills of cyanocobalamine. For the last 5 years I have been having some serious symptoms that seem to be getting worse. I’m constantly cold and pins and needles are getting worse. I cannot get ONE doctor who is really thorough and can give me answers that improve my quality of life.
All B12 in supplements is synthetic. They produce it in the hydroxocobalamin form in vats of bacteria. Then add the cyano- to improve stability of the compound. Whatever the questions over cyanocobalamin, it isn’t a matter of being produced naturally or synthetically. Also, hydroxycobalamin is usually called hydroxocobalamin (with an ‘o’ rather than a ‘y’).
Hello Doctor, im dealing with a tough situation of what presumably seems to be some sort of TMJ, and both my teeth and jaws creats so much pressure on my body that it creates Fibromialgia and also IBS GERD.. Only lately i came to understand and experience that it is created directly from my jaws and teeth. Regarding the B12 vitamin, in the past i used to take the Methyl one, but it allways gave me bad stomach issues and heartburns so i stopped. Now days i wish to resume taking it, specifically because of my severe muscle cramps all over, which one would you think would be best taking out of the options you’ve mentioned, and hopefully taking it by regular swolloing capsules or sublingual, And where do i find it? Many thanks to you
Hi, Dr Childs Your explanation for this article is in-depth for layman like me, for the different forms of vitamin b12. Will you doing article for best and worst form of B1 and B6; which i think its sufficiency are good for mental health among the many B-complex elements, ie B1, B5, B6, B9, B12 etc. With the best form of B1 and B6, i can then be able to select the type of B1 and B6’s vitamin forms and thereby narrowing the brand of B1 and B6 vitamins to purchase. With regards Eric Teo
Will high dosages like 3000mcg that you’re suggesting not deplete potassium? This is the only reason I’m scared to take higher dosages which would likely help my health problems. Also is it true hydroxycolabam form cures Candida?? I’m trying to get my gut Candida issue under control and scared the methycolabalm is making it worse
I am hypothyroide patient with autoimmune gastritis due to pernicious anemia. I need your help to just for me a supplement that can help me. Should i take injections better?. I live in Germany where there is only hydroxy cobalamin and cyanocobalamin as injection. i really don’t know can you please suggest how to start the therapy.
i get injections every 4 months last time i got one i asked what was the form and she said it was cyanocobalamin, it does nothing for me. after my injection i can be days with low energy like my body its telling me its not liking it at all. what would you recommend as a different injection? also last blood work my vitamin D level was 25. i cannot seem to find any right vitamin d in phamacies that help.
I’ve read that both Vit B12 and Vit D are hard for our bodies to absorb due to lowered stomach acids in most people now and that highly absorbable oral doses a.. I re best.. This is esp true in people over 50 but with all the gmo’ing and other things it’s probably true of younger folks now too.. I heard someone explain that the cyanide really isn’t a problem because it is not really absorbed by the body ..can’t remember why
The only YouTube article I’ve watched so far where a doctor actually knows what he’s talking about when it comes to B12! Everyone wants him to just tell them the one single B12 form to take. But that wouldn’t be the correct answer because of all the things he said in the article. And if you are mad at his explanation, then you are impatient and lazy and don’t want to do any research but just want someone to blindly tell you what to take. The entire problem with today’s population!
Interesting article I inject cyno and hydroxy and eat high meat diet and still feel as though I’m deficient 🤔 I have high levels in the blood and taking magnesium and my folate and iron levels are normal range.. i have verticle lines on my nails, white on my lower lip, white nails with red strip across the top, fatigued and feel exercise intolerant. I did do a thyroid test and my TSH is 4.01 and i recently had gallbladder surgery which i know can cause b vitamin deficiencys too
I will watch this after I get out of medical school. Sounds like I will be dead by then. I have been studying and living my life the most healthiest way possible. I am very smart and feel I stay up to date even a bit OCD about it. I have top DRS at the TOP hospitals in the world and always reading and taking the newest classes at Various Medical schools. I can converse on most any subject but unless you are just a Narcissist feeding your ego, I will not watch your website anymore. I am unsubscribing now.