Harpers

VITAMINS & MINERALS / 489H 3 CNNH 3 C NH 2CH 2NSCH 2CH 2 OHO OCH 2 CH 2 O P O P OO OH 3 CNCH 2S+HThiamin Thiamin diphosphate CarbanionFigure 45–9.Thiamin, thiamin diphosphate, and the carbanion form.genase in the citric acid cycle; and the branched-chainketo-acid dehydrogenase involved in the metabolism ofleucine, isoleucine, and valine. It is also the coenzymefor transketolase, in the pentose phosphate pathway. Ineach case, the thiamin diphosphate provides a reactivecarbon on the thiazole moiety that forms a carbanion,which then adds to the carbonyl group of, for instance,pyruvate. The addition compound then decarboxylates,eliminating CO 2 . Electrical stimulation of nerve leadsto a fall in membrane thiamin triphosphate and releaseof free thiamin. It is likely that thiamin triphosphateacts as a phosphate donor for phosphorylation of thenerve membrane sodium transport channel.Thiamin Deficiency Affectsthe Nervous System & HeartThiamin deficiency can result in three distinct syndromes:a chronic peripheral neuritis, beriberi, whichmay or may not be associated with heart failure andedema; acute pernicious (fulminating) beriberi (shoshinberiberi), in which heart failure and metabolic abnormalitiespredominate, without peripheral neuritis; andWernicke’s encephalopathy with Korsakoff’s psychosis,which is associated especially with alcohol anddrug abuse. The central role of thiamin diphosphate inpyruvate dehydrogenase means that in deficiency there isimpaired conversion of pyruvate to acetyl CoA. In subjectson a relatively high carbohydrate diet, this results inincreased plasma concentrations of lactate and pyruvate,which may cause life-threatening lactic acidosis.Thiamin Nutritional Status CanBe Assessed by ErythrocyteTransketolase ActivationThe activation of apo-transketolase(the enzyme protein)in erythrocyte lysate by thiamin diphosphateadded in vitro has become the accepted index of thiaminnutritional status.VITAMIN B 2 (RIBOFLAVIN) HASA CENTRAL ROLE IN ENERGY-YIELDING METABOLISMRiboflavin fulfills its role in metabolism as the coenzymesflavin mononucleotide (FMN) and flavin adeninedinucleotide (FAD) (Figure 45–10). FMN is formed byATP-dependent phosphorylation of riboflavin, whereasFAD is synthesized by further reaction of FMN withATP in which its AMP moiety is transferred to theOHOHOHOHOHOHOCH 2CHCHCHCH 2 OHCH 2CHCHCHCH 2OPOH 3 C N NOH 3 C N NH 3 C NNH 3 C NNOORiboflavinFMNH 3 C N NOH OH OHCH 2 CH CH CH CH 2OH 3 C NNOFADO OOOH OHNNCH 2NH 2O P O P OO N NO OFigure 45–10. Riboflavin and the coenzymes flavin mononucleotide (FMN) and flavinadenine dinucleotide (FAD).O