Question

why is pyruvate dehydrogenase the regulated enzyme of pdc but not dihydrolipoyl transacetylase or dihydrolipoyl dehydrogenase?

what causes defective regulation of pdc?

if cells have energy, it will not run PDC instead what will it run?

Answer 1

The three enzymes in the Phosphate Dehydrogenase Complex (PDC) which catalyze the different steps of pyruvate to Acetyl coA are:

Enzyme 1: Pyruvate dehydrogenase

Enzyme 2: Dihydrolipoyl transacetylase

Enzyme 3: Dihydrolipoyl dehydrogenase

Thymine pyrophosphate (TPP) is located in the pyruvate dehydrogenase (E1). The first imprtant reaction in the PDC are 2 carbons from pyruvate are added to TPP on complex I. One of the pyruvate carbons is lost as CO2. During the process the acetyl group also gets reduced when added to TPP. This is the only irreversible reaction of the entire PDC but makes the whole reaction irreversible.

There are two ways that regulate the PDC i. Product inhibition and ii. Covalent modification

Why is pyruvate dehydrogenase the regulated enzyme of pdc but not dihydrolipoyl transacetylase or dihydrolipoyl dehydrogenase?

Covalent modification of the E1 enzyme Pyruvate dehydrogenase, which will result in accumulation of acetyl CoA which will activate pyruvate dehydrogenase kinase that phosphorylates the E1 complex making it inactive so that acetyl group from pyruvate cannot attach to TPP by which the PDC reaction does not occur. Since, the Dihydroliolyl transacetylase or Dihydrolipoyl dehyrdrogenase are the 2nd and 3 rd steps but Pyruvate dehydrogenase being first step makes it most important regulated enzyme in the complex.

What causes defective regulation of pdc?

Pyruvate is decarboxylated and attached to TPP at E1 Pyruvate decarboxylase. The most common defect in this regulation of PDC is defect in alpha subunit of E1 (common genetic effect) which disrupts the regulation of pdc.

Thiamine (Vitamin B1) is essential for TPP, Pantothenate (Vitamin B5) is required for Coenzyme A, Niacin (Vitamin B3) is essential for NAD+, Vitamin B2 riboflavin is required for FAD. Hence, deficiency of these enzymes would also result in defective regulation.

if cells have energy, it will not run PDC instead what will it run?

Glycolysis and Gluoconeogenesis occurs