Lipothiamide pyrophosphate

Lipothiamide pyrophosphate, LTPP (reduced) LTPP (oxidized) -0.42... 

Lipothiamide pyrophosphate (LTPP) is a compound postulated by Reed (26) to account for the biological activity of a-lipoic acid. It is not certain that such a compound does exist however, a-lipoic acid and thiamine pyrophosphate do act in oxidation-reduction reactions. 

Reed and De Busk have suggested that the true coenzyme form of lipoic acid is a conjugate of a-lipoic acid and thiamine pyrophosphate, given the name lipothiamide. The bond between the two is presumed to be a peptide bond between the amino group on Ci of the pyrimidine moiety of thiamine and the carboxyl group of a-lipoic acid. The true coenzyme is reported to be the lipothiamide pyrophosphate. 

Even more recently, Reed and DeBusk have observed that lipothiamide pyrophosphate is required for pyruvate dismutation and a-keto-glutarate oxidation by soluble enzyme preparations from an E. coli mutant. They suggest that the initial step in the oxidative decarboxylation of a-keto acids is the formation of an acyl lipothiamide pyrophosphate complex. In a subsequent step, they assume that the acyl group is transferred to CoA. These observations cast considerable light on the mechanism of the oxidative decarboxylation of a-keto acids and certainly may explain some of the difficulties already discussed in the section on TPP. However it remains to be seen whethei lipothiamide pyrophosphate carries the acyl group as a thioester as in CoA, and whether it acts exclusively as an acyl carrier and not also as a hydrogen carrier. One point which is still not clear is whether the oxidation and decarboxylation occur simultaneously or in an orderly sequence. 

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