Fates of Pyruvate under Anaerobic Conditions: Fermentation:- Thiamine Pyrophosphate Carries “Active Acetaldehyde” Groups
The pyruvate decarboxylase reaction provides our first encounter with thiamine pyrophosphate (TPP) (Fig. 14–13), a coenzyme derived from vitamin B1. Lack of vitamin B1 in the human diet leads to the condition known as beriberi, characterized by an accumulation of body fluids (swelling), pain, paralysis, and ultimately death. Thiamine pyrophosphate plays an important role in the cleavage of bonds adjacent to a carbonyl group, such as the decarboxylation of -keto acids, and in chemical rearrangements in which an activated acetaldehyde group is transferred from one carbon atom to another (Table 14–1). The functional part of TPP, the thiazolium ring, has a relatively acidic proton at C-2. Loss of this
MECHANISMFIGURE 14–13 Thiamine pyrophosphate (TPP) and its role in pyruvate decarboxylation. (a) TPP is the coenzyme form of vitamin B1 (thiamine). The reactive carbon atom in the thiazolium ring of TPP is shown in red. In the reaction catalyzed by pyruvate decarboxylase, two of the three carbons of pyruvate are carried transiently on TPP in the form of a hydroxyethyl, or “active acetaldehyde,” group (b), which is subsequently released as acetaldehyde. (c)After cleavage of a carbon–carbon bond, one product often has a free electron pair, or carbanion, which because of its strong tendency to form a new bond is generally unstable. The thiazolium ring of TPP stabilizes carbanion intermediates by providing an electrophilic (electron-deficient) structure into which the carbanion electrons can be delocalized by resonance. Structures with this property, often called “electron sinks,” play a role in many biochemical reactions. This principle is illustrated here for the reaction catalyzed by pyruvate decarboxylase. 1The TPP carbanion acts as a nucleophile, attacking the carbonyl group of pyruvate. 2Decarboxylation produces a carbanion that is stabilized by the thiazolium ring. 3Protonation to form hydroxyethyl TPP is followed by 4 release of acetaldehyde. 5A proton dissociates to regenerate the carbanion.
proton produces a carbanion that is the active species in TPP-dependent reactions (Fig. 14–13). The carbanion readily adds to carbonyl groups, and the thiazolium ring is thereby positioned to act as an “electron sink” that greatly facilitates reactions such as the decarboxylation catalyzed by pyruvate decarboxylase.
