Ho Oh

The overall reaction is: _¿-¿— + FAD f™*™6» V^ + FADH?

Figure 2.10 Flavin adenine dinucleotide, FAD, oxidized and reducedforms. The two circled hydrogen atoms in FADH2 are those removed from carbons

2.2.4 Thiamine Diphosphate

Thiamine diphosphate is a particularly interesting substance because it illustrates a chemical evolution from lactic acid bacteria to yeasts and then to higher animals. It converts pyruvic acid, which is an a-keto-acid, into the equivalent of a p-keto-acid (with C=N+ instead of C=0), which can then lose C02 by decarboxylation. We know that the hydrogen atom next to nitrogen in the thiazole ring is acidic and easily removed because if we shake thiamine with D20, we get rapid exchange of that atom (Figure 2.11).

Some simple bacteria, such as those that produce yoghurt, reduce the pyruvic acid to lactic acid, and the reaction stops there, without much of ch h3c n^nh2 ch h2 4 lv. n n çh3

^c-nH £ = ^ V cr-- ^Vs h2 vs h+ u j h ci" ° cl"

thiamine diphosphate (p) = phosphate

Figure 2.11 Thiamine diphosphate exchanges one labile hydrogen atom with D20, indicating the reactive centre o oh

1 Hi oh " oh lactic acid

Figure 2.12 The reduction of pyruvic acid to lactic acid with the consumption of NADH formed earlier in the degradation of glucose the energy of glucose being released (Figure 2.12). For each molecule of glucose that is broken down in metabolism, two molecules of NAD+ are required (see Figure 2.20). Eventually two molecules of pyruvic acid are produced together with two molecules of NADH + H+. The NADH produced in catabolism of glucose is used by the lactic acid bacteria to reduce the pyruvic acid.

CH3 CHg CH3 CH,

hs A

enzyme Vn3

cr No

The overall reaction is: CH3COCOOH -- CH3CHO + C02

Figure 2.13 The reaction of thiamine diphosphate with pyruvic acid in yeasts to release carbon dioxide and give acetaldehyde, and then ethanol. The structure marked A is used again in Figure 2.14

More advanced organisms, like yeasts, can use thiamine diphosphate with different enzymes to oxidize glucose to ethanol and carbon dioxide (Figure 2.13). The NADH produced in the glucose break-down is then used to reduce acetaldehyde to ethanol. Yeast is therefore used by the brewer for the alcohol produced and by the baker for the C02 to aerate the bread.

Higher organisms have evolved a system to oxidize the pyruvic acid further, with a substance called lipoic acid as an intermediate, to acetic acid (as CoA thioester) and C02 (continuing the reaction from stage A in Figure 2.13). Approximately half the C02 we exhale is produced by decarboxylation with thiamine. The lipoic acid inserts itself after the decarboxylation step (Figure 2.14). The acetyl coenzyme A produced in the last step is either ultimately oxidized to C02 (through the citric acid or Krebs cycle) or it is the vital starting material for the biosynthesis of fatty acids, acetogenins and terpenes (Figure 1.1).

-N^s CI- — h3c-c—s sh part of lipoic acid h3c-<0shs

CoASH

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