Resumo de Vitamin B-12 - Tracy W. Burke

COBALAMIN (Vitamin B-12, Cyanocobalamin)Cobalaminis more commonly known as Vitamin B12.Vitamin B12 is composed of a complex tetrapyrrol ring structure(corrin ring) and a cobalt ion in the center. Vitamin B12 issynthesized exclusively by microorganisms and is found in the liver of animalsbound to protein as methycobalamin or 5'-deoxyadenosylcobalamin. The vitaminmust be hydrolyzed from protein in order to be active. Hydrolysis occurs in thestomach by gastric acids or the intestines by trypsin digestion followingconsumption of animal meat. The vitamin is then bound by intrinsic factor, a protein secretedby parietal cells of the stomach, and carried to the ileum where it isabsorbed. Following absorption the vitamin is transported to the liver in theblood bound to transcobalamin II.Thereare only two clinically significant reactions in the body that require vitaminB12 as a cofactor. During the catabolism of fatty acids with an oddnumber of carbon atoms and the amino acids valine, isoleucine and threonine theresultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCAcycle. One of the enzymes in this pathway, methylmalonyl-CoA mutase, requiresvitamin B12 as a cofactor in the conversion of methylmalonyl-CoA tosuccinyl-CoA. The 5'-deoxyadenosine derivative of cobalamin is required forthis reaction. The second reaction requiring vitamin B12 catalyzes theconversion of homocysteine to methionine and is catalyzed by methioninesynthase. This reaction results in the transfer of the methyl group from N5-methyltetrahydrofolateto hydroxycobalamin generating tetrahydrofolate (THF) and methylcobalaminduring the process of the conversion. This vitamin builds up nervous system,increases energy helps in the formation and regeneration of red blood cells,thus helping prevent anemia; necessary for carbohydrate, fat and proteinmetabolism. It maintains a healthy nervous system, promotes growth in children,increases energy; and is needed for Calcium absorption.A deficiency of vitamin B 12 may lead to poorappetite, growth failure in children, tiredness, brain damage, nervousness,neuritis, degeneration of spinal cord, depression, lack of balance, orPernicious anemia. The liver canstore up to seven years worth of vitamin B12. Pernicious anemia is a megaloblastic anemiaresulting from vitamin B12 deficiency that develops as a result alack of intrinsic factor in the stomach leading to malabsorption of thevitamin. The anemia results from impaired DNA synthesis due to a block inpurine and thymidine biosynthesis. The block in nucleotide biosynthesis is aconsequence of the effect of vitamin B12 on folate metabolism. Whenvitamin B12 is deficient essentially all of the folate becomestrapped as the N5-methylTHF derivative as a result of the loss offunctional methionine synthase. This trapping prevents the synthesis of otherTHF derivatives required for the purine and thymidine nucleotide biosynthesispathways. Neurologicalcomplications also are associated with vitamin B12 deficiency andresult from a progressive demyelination of nerve cells. The demyelination isthought to result from the increase in methylmalonyl-CoA that results fromvitamin B12 deficiency. Methylmalonyl-CoA is a competitive inhibitorof malonyl-CoA in fatty acid biosynthesis as well as being able to substitutefor malonyl-CoA in any fatty acid biosynthesis that may occur. Since the myelinsheath is in continual flux the methylmalonyl-CoA-induced inhibition of fattyacid synthesis results in the eventual destruction of the sheath. Theincorporation methylmalonyl-CoA into fatty acid biosynthesis results inbranched-chain fatty acids being produced that may severely alter thearchitecture of the normal membrane structure of nerve cells

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