Metabolism 2 Study guide Exam 4Riboflavin-B21. What is the active form?- Riboflavin is the basis of two other coenzymes that we have covered many times in metabolism 1: FAD and FMN. It is another of the B vitamins or water soluble.- Riboflavin is a cyclic molecule, that when phosphorylated, forms FMN and then FAD. FAD is the electron carrier in the citric acid cycle and produces ATP in the electron transport chain. FAD is flavin adenine dinucleotide and FMN is flavin mononucleotide. 2. What are the sources?- Riboflavin is widespread is milk and dairy products and in most meats. If grains are enriched, then it will be there. This B vitamin is very light sensitive and UV light will easily destroy it. It is stable is cooking and processing though3. How is it absorbed, digested, transported, and stored?- Like every other vitamin gone over, first the protein part have to be removed or in other words, it has to be hydrolyzed. Good ole’ HCl helps this process to remove the proteins. So if it is eaten as FAD and FMN, it is first hydrolyzed and the riboflavin must be in its free form to be absorbed. This is done by the two enzymes FAD pyrophosphatase and FMN phosphatase. HCl only removes the proteins.- Now that we have are free riboflavin, it is absorbed via active transport mostly. Once it enters the mucosal cells and this is phosphorylated back to FMN via the enzyme flavokinase. After the mucosal layer, at the serosal layer some of that FMN we just formed returns back to free riboflavinand is then shunted to the liver. It is stored as FAD. So it seems there was some unnecessary back and forth. Free riboflavin form FMN in the mucosal layer, then went back to riboflavin in the serosal, and then goes to FAD in the liver. The body gets confusing at times. 4. What are the functions of riboflavin?- Its main function is as an electron carrier as FAD. It is reduced in the TCA cycle to FADH and then oxidized in the electron transport chain to provide the potential to produce ATP- It also helps to reduce glutathione to GSH. 5. What is the deficiency of riboflavin?- Populations most likely to be deficient in this vitamin are those that are lactating or pregnant, alcoholics, and elderly. You will start to see a pattern in these populations. Alcoholics are at risk for all deficiencies, asare elderly’s, as they generally have poor nutrition. Pregnant women need more of the same vitamins for the fetus. - Those in some clinical situations also have a risk, simply because their body might not be able to handle digestion and the absorption.- Infants with hyperbilirubinemia on photo therapy should be given extra riboflavin. The photo therapy destroys it, if you remember that it is very light sensitive. - When a deficiency does develop, it will lead to glossitis and stomatitis, skin changes, and peripheral neuropathy. 6. How to assess it and what is the DRI?- The best way to assess one’s status for riboflavin is to look at their activity of the RBC glutathione reductase, because as you recall, FAD is required for this reaction. FAD will convert the GSSG (with the help of NADPH) to GSH, so without riboflavin, that meansno FAD, and no GSH. They measure the reaction based on if another reactant, NADPH is used. This is easy to measure.Niacin-B31. What is the active form?- Niacin forms the other electron carrier in ATP production, NAD. It is either referred to as nicotinic acid or nicotinamide in its active form. When one of these forms attaches to a ribose and adenosine, you get a NAD. Then this is what is reduced in the TCA cycle to NADH and this is oxidized to NAD in the electron transportchain. 2. What are the sources?- Niacin is best found in meat and fish. It is in its free form, nicotinamide, here, so these are the best sources. Remember that our body always absorbs the free form for everything - Meat and fish are the best sources, but we can also get niacin from cereals, legumes, seeds, coffee,and tea to an extent. - Corn is noted as a poor source, so that means that you should defiantly know that. It is poor because it is low in tryptophan (this can form niacin in the body) and the niacin in the corn is unavailable. Lime water can free the niacin for us though. - Now to what we can make: The body can form niacin from the amino acid tryptophan. It takes 60mg of tryptophan to form 1mg niacin. This is referred to as a niacin equivalent. 3. What are the functions of niacin?- Niacin helps around 200 enzymes to function, because all B vitamins are coenzmyes. As NAD, it works in metabolism to pick up electrons by being reduced to NADH. NAD is present is glycolysis, the TCA cycle, and beta oxidation, As NADH, it is now in its reduced form and this transfers the electrons to the electron transport chain. NADP is present in the hexose phosphate shunt and in the maltate shuttle system. That is all that you need to know about NADP. NADHP is required for fatty acid synthesis, to reduce cholesterol, to make DNA precursors, and itis one of the reactants in that glutathione reaction that is talked about so much. Know that it is areducing agent for all the above.4. What does a deficiency lead to?- The DRI is 14 NE/day or niacin equivalents. 1 NE is equal to either 1 mg niacin, 60 mg tryptophan, or 6000 mg protein. Remember that 60 mg tryptophan can form 1 mg niacin. And the assumption is if you have 6000 mg protein, you probably have 60 mg tryptophan in there. (1000 mg = 10 mg tryptophan) A deficiency will lead to pellagra, which is the famed 4D’s. Dermantitis, Diarrhea, Dementia, and finally Death- For people at risk, we have people with increase energy requirements. One drug does interfere with niacin and that is isoniazid, so defiantly know that. - If you have a deficiency in tryptophan or a problem with its metabolism, this will put you at an increased risk. The example for this is Hartnup disease. 5. Is there a toxicity?- Niacin, in excessive, is used to lower lipid levels. Namely, LDL, VLDL, and increase HDL. The only side effect with this is it causes the sudden release of histamine, which is an inflammatory marker. This causes flushing of the skin and will lead to itching and gastrointestinal problems.6. How do you assess it?- Simply look at the urinary excretion of N’methyl nictotinamide after a 50 mg test dose. Based on this number, you can determine their level Below 0.5 is considered deficient, 0.5-1.59 is marginal, and above 1.6 is
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