The Krebs Cycle: Reactions and Metabolic Pathways

This set covers the eight enzymatic reactions of the Krebs Cycle, their regulation mechanisms, cofactors, and associated clinical conditions.

The Krebs Cycle

Also known as the citric acid cycle or the tricarboxylic acid cycle, it consists of 8 metabolic reactions involved in the full oxidation of food molecules into $CO_{2}$.

Oxaloacetate

The starting and regenerated metabolite of the Krebs Cycle that combines with an acetyl group to begin the reaction cycle.

Citrate Synthase

The enzyme that catalyzes Reaction 1, the formation of citrate from acetyl-CoA and oxaloacetate while releasing CoASH.

Aconitase

The enzyme responsible for the isomerization of citrate to isocitrate via the formation of a $cis$-aconitate intermediate.

Isocitrate Dehydrogenase

The enzyme that catalyzes the oxidation and decarboxylation of isocitrate to form $\alpha$-ketoglutarate, producing $NADH$ and releasing $CO_{2}$.

Isocitrate Dehydrogenase Cofactors

The reaction mechanism for this enzyme involves $NAD^{+}$ and $Mg^{2+}$ as essential cofactors.

$\alpha$-Ketoglutarate Dehydrogenase (KGDH)

A complex that liberates $CO_{2}$ and $NADH$ to form Succinyl-CoA, utilizing $CoASH$ as a substrate and TPP, Lipoamide, FAD, and $NAD^{+}$ as cofactors.

Succinyl-CoA Synthetase

The enzyme that performs substrate-level phosphorylation to create a molecule of GTP from GDP and Pi while releasing Succinate and Coenzyme A.

Succinate Dehydrogenase

An oxidoreductase and membrane-bound protein (Complex II in the electron transport chain) that oxidizes succinate to fumarate while transferring electrons to FAD.

Fumarase

A hydrolase enzyme that converts fumarate to malate by incorporating a molecule of water ($H_{2}O$).

Malate Dehydrogenase

The enzyme that catalyzes the final reaction of the cycle, oxidizing malate to regenerate oxaloacetate and forming one molecule of $NADH$ and $H^{+}$.

Total Energy Yield (Per Glucose Molecule)

The result of two full Krebs cycle turns: $6\,NADH/H^{+}$, $2\,FADH_{2}$, and $2\,GTP$ (ATP equivalents).

Pyruvate Dehydrogenase (PDH) Regulation

Known as the gatekeeper of the Krebs Cycle, it is inactivated by high levels of $NADH$, Acetyl-CoA, or ATP, and by phosphorylation via PDH kinases.

Beriberi

A disease state caused by a lack of Vitamin B1, leading to inefficient TPP production and reduced capacity of the PDH and KGDH complexes.

Substrate-Level Phosphorylation

The metabolic process occurring in Reaction 5 where GTP is formed through the phosphorylation of GDP by Succinyl-CoA Synthetase.