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Metabolism 2 Study guide Exam 4Folate and Water Soluble Vitamins1. What are vitamins and difference between fat and water soluble? - Repeating this question, since she asks so many times. They are micronutrients that must be supplied from the diet. Needed for normal function and their absence cause certain symptoms with each one. The body can make some, but not in appreciable amounts. Fat soluble is obviouslysoluble in fat, stored in the body in large amounts so it’s not required every day. Since it’s stored, defiency takes a long time to occur. Most have precursors, and only higher organisms need them. Can be toxic at low amounts (but still way higher than the UL). Water soluble are stored minimally, excreted in the urine, so defiency can happen much faster. Absorbed into blood, since water soluble and both simple and complex organisms need. Since they aren’t really stored, they are only toxic at mega doses (100x DRI)2. What is the synthesis of folic acid (folate)?- Folate can have up to 9 different residues, with the important ones being pteridine, PABA, and glutamic acid. KNOW THESE!- You need all of these components to form out folic acid, and the body can make all of them exceptpteroic acid. Always know the “excepts”. So this is why it must by consumed; we can’t form pteroicacid. 3. How is it absorbed and metabolized?- Like all other vitamins, it is present in food as one type and we need it in another form to absorb. For foltate, it is in food as polyglutamate and we have to hydrolyze it to monoglutamate. This is done via the conjugase enzymes, and they depend on zinc. So if you are zinc deficient, you will have a hard time absorbing foltate.  Some foods also contain conjugase inhibitors, such as legumes, lentils, oranges, and cabbages. Soa diet high in these is not ideal for folate status - So now we have it done to its monoglutamate form. Now what? This is reduced in the intestinal cells to the active forms, THF and DHF. It is half stored in the liver as THF. 4. What are the functions of folic acid?- Like all the B vitamins, folic acid is a coenzyme involved in energy production. Specifically, the reactions that involve carbohydrate transfers (in the form of methyl) use folic acid. There are three metabolites that participate in these reactions that you will have to know. Learnthose.- One very important reaction is the resynthesis of methionine from homocysteine. Homocysteine isformed from the breakdown of methionine (used for epinephrine synthesis). If this builds up, it can be toxic to the body. So folate (as THF) and vitamin B12 are used to regenerate methionine.  It starts with 5-methyl THF acting with vitamin B12 to form methylcobalamin. So it is simply passing the methyl group to the vitamin B12. The 5-methyl THF loses the methyl and becomes THF. This is will resynthesized back the 5-methyl THF. Methylcobalamin then will transfer this methyl group to homocysteine to reform methionine. This is done via methionine synthase (very simple to remember; it synthases methionine). - Now to quickly go over how methionine breaks down to homocysteine: Methionine acts with a transferase to form SAM. Then SAM will give its methyl away to form SAH, then finally homocysteine. - It is also used in the synthesis of DNA and RNA and the metabolism of some amino acids (glycine toserine by donating a methyl group, histidine). 5-methyl THF is always the starting coenzyme. Glycine to serine depends on the tissue of which amino acid will form predominantly. 5. What are the sources of folate?- This is widespread in green vegetables, oranges, organ meats, and yeast. Some things to note are it is higher in raw foods; heating and cooking destroys folate. 6. What does a deficiency lead to?- The DRI is measured as dietary folate equivalents or DFE. A DFE is equal the food folate plus 1.7xugof synthetic folate. I would just know what a DFE is in case she asks. A deficiency can arise from prolonged cooking (since cooking destroys folate), and metabolism problems. And alcoholics of course. Drugs that interact with folate metabolism are methotrexate (this is a type of chemotherapy) andanticonvulsants.  If you are vitamin B12 deficient, then this increases your risk. - Now what does it lead to?? A deficiency will lead to an altered shape and function to the RBC. Termed megaloblastic, macrocytic anemia.  In women, folate is very important in neural tube development of the fetus. Without folate, the spinal cord will not develop correctly and can protrude from the body—called spina bifida. 7. How do we assess the levels of folate?- Looking at the RBC folate levels, we can get a long term status and looking at the plasma levels, wecan get a short term status.  One thing to note though, is that folate levels depend on vitamin B12. Called the methyl folate trap, all this is saying is that if you are deficient in B12, you can’t form THF. Remember from the methionine resythesis reaction that 5-methyl THF acts with B12 to form THF and methylcobalamin. Without B12, we can’t form THF (which if you recall, is the active form of folate.)Cobalamin-B121. What is the active form of this vitamin?- The forms of vitamin B12 are also known as corrinoids, and there are multiple forms. They all have4 rings surrounding the cobalamin. There are many forms: The two active forms are 5-deoxyadenosylcobalamin, which has 4 deoxys, and methylcobalamin,which has 4 methyl’s. All the other forms can also be converted into these.2. How is it absorbed?- This vitamin has the most complicated absorption.  So first the pepsin releases the cobalamin from its ring structure, and the cobalamin binds to an “R” protein, and then travels to the small intestine. In the first part, the duodenum, the “R” protein is hydrolyzed and then the cobalamin binds then something called Intrinsic Factor, which is made in the stomach.  Now it gets absorbed in the ileum, where the receptors are. Once the cobalamin is in the blood,it then binds to either Transcobalmin 1, 2, or 3. (Although 2 is the most common one) And then it is stored in the liver mostly and some in the muscles. Although a water soluble vitamin, it is stored better than most others, so deficiency take several years to occur. Bacteria in the intestinal also can make a little.3. What are the sources?- This vitamin is only in animal products, so if you are a vegetarian, you need to get your B12


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FSU HUN 3226 - Metabolism 2 Study guide Exam 4

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