1 - Entry of Pyruvate

What are the two main types of carbon-carbon (C–C) bond cleavage reactions used in biological systems?

• Alpha-cleavage (α-cleavage)

• Cleavage between alpha and beta carbons (α-β cleavage)

What is required for an alpha-cleavage (α-cleavage) reaction to occur?

The carbon undergoing cleavage must be attached to a hydroxyl group or a carbonyl (ketone) group. This typically results in decarboxylation reactions

What is required for a carbon-carbon bond cleavage between the α and β carbons?

A carbonyl (ketone) or carboxylic acid group must be present; the cleavage occurs between the α and β carbons relative to that group.

Which enzyme complex uses an α-cleavage in its catalytic mechanism?

The Pyruvate Dehydrogenase Complex performs an oxidative decarboxylation of pyruvate via an α-cleavage

Which reactions in the TCA cycle involve C–C bond cleavage?

• Isocitrate → α-ketoglutarate (α-β cleavage)

• α-ketoglutarate → succinyl-CoA (α-cleavage)

What enzyme complex converts pyruvate into acetyl-CoA?

The Pyruvate Dehydrogenase Complex (PDC)

What is the overall reaction catalyzed by the Pyruvate Dehydrogenase Complex?

Pyruvate + CoA + NAD⁺ → Acetyl-CoA + CO₂ + NADH

Is the conversion of pyruvate to acetyl-CoA reversible in mammalian cells?

No, it is irreversible in mammalian cells.

Why is the conversion of pyruvate to acetyl-CoA considered a metabolic decision point?

Because once pyruvate is converted to acetyl-CoA, it can no longer be converted back into glucose; the cell must decide between using it for energy or biosynthesis

What type of reaction is the decarboxylation of pyruvate by the Pyruvate Dehydrogenase Complex?

It is an oxidative decarboxylation involving an α-cleavage

What molecule carries the acetate fragment into the TCA cycle after pyruvate is converted?

Coenzyme A (CoA), forming acetyl-CoA

What is the metabolic role of acetyl-CoA after its formation from pyruvate?

Acetyl-CoA serves as the fuel for the TCA cycle and is a precursor for fatty acid, cholesterol, and isoprenoid biosynthesis