CLINICAL CASES
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The E1 and E2 components are specific for each of the pyruvate dehy-
drogenase, a-ketoglutarate dehydrogenase, and branched-chain a-keto
acid dehydrogenase complexes. However, the E3 component is identical for
all of the enzymes.
Thiamine pyrophosphate is also an important cofactor for the transketolase
reactions in the pentose phosphate pathway of carbohydrate metabolism
(Figure 15-3). These reactions are important in the reversible transformation
of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-
eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring
of TPP that reacts with a ketose phosphate (xylulose 5-phosphate) to cause
the release of an aldose phosphate with two fewer carbons (glyceraldehyde
3-phosphate). The TPP-bound glycoaldehyde unit is then transferred to a different
aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a
ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or
fructose 6-phosphate).
A deficiency in thiamine will decrease the efficiency of the enzymes for
which TPP is required as a cofactor. Thus, the rate of conversion of pyruvate
to acetyl-CoA and the flow of acetyl-CoA through the tricarboxylic acid cycle
will be depressed as a result of the inefficiency of the TPP-requiring enzymes
pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. The production of
the reduced electron carrier, NADH, and the ATP produced from it via oxidative
phosphorylation will be decreased as a consequence. Because nervous tissue
and heart use at high rates ATP synthesized from the oxidation of NADH
produced from pyruvate conversion to acetyl-CoA and from the TCA cycle,
these tissues are most affected by a deficiency in thiamine. When deficient in
thiamine, the brain can no longer efficiently metabolize pyruvate through the
TCA cycle to produce ATP and thus must convert it to lactate to produce ATP.
Figure 15-3. The reaction catalyzed by the enzyme transketolase, which trans-
fers a glycoaldehyde group from a ketose to an aldose.
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