Krebs Cycle and Cellular Bioenergetics

Vocabulary flashcards covering the enzymes, reactions, cofactors, energy yield calculations, and regulation of the Citric Acid Cycle (Krebs Cycle).

Citric Acid Cycle (CAC)

The final common pathway occurring in the mitochondrial matrix for the complete oxidation of acetyl-CoA obtained from the partial oxidation of carbohydrates, lipids, and proteins.

Cellular Site of the Citric Acid Cycle

The mitochondrial matrix of every cell containing mitochondria; it does not occur in mature red blood cells (RBCs) because they lack mitochondria.

Hans Krebs

The biochemist (1900–1981) who elucidated the tricarboxylic acid cycle, also known as the Krebs cycle or citric acid cycle.

Citrate Synthase

The enzyme that catalyzes the first step of the citric acid cycle: the condensation of acetyl-CoA and oxaloacetic acid to form citric acid.

Aconitase

The enzyme that catalyzes the isomerization of citric acid to isocitrate in step 2 of the citric acid cycle.

Isocitrate Dehydrogenase

The enzyme that catalyzes the oxidation of isocitrate to $\alpha$-ketoglutarate, releasing $\text{CO}_2$ and producing $1\,\text{NADH}$.

$\alpha$-Ketoglutarate Dehydrogenase Complex

A multi-enzyme complex analogous to pyruvate dehydrogenase that converts $\alpha$-ketoglutarate to succinyl-CoA, releasing $\text{CO}_2$, generating $1\,\text{NADH}$, and requiring five specific coenzymes.

Coenzymes of the $\alpha$-Ketoglutarate Dehydrogenase Complex

Five required cofactors: thiamin pyrophosphate (TPP), lipoic acid, coenzyme A (CoA-SH), FAD, and $\text{NAD}^+$.

Succinate Thiokinase

The enzyme that cleaves the high-energy thioester bond of succinyl-CoA to form succinate, driving the synthesis of $1\,\text{GTP}$ ($1\,\text{ATP}$) from GDP and inorganic phosphate ($\text{P}_i$) via substrate-level phosphorylation.

Succinate Dehydrogenase

The enzyme that oxidizes succinate to fumarate while reducing FAD to $\text{FADH}_2$.

Fumarase

The enzyme that catalyzes the hydration of fumarate to form malate.

Malate Dehydrogenase

The enzyme that oxidizes malate to regenerate oxaloacetate, reducing $\text{NAD}^+$ to NADH.

Oxaloacetic Acid Recycling

The principle that oxaloacetate regenerated in the final reaction of the cycle reinitiates the pathway with another molecule of acetyl-CoA, resulting in zero net consumption of oxaloacetate.

Net Energy Yield of One Acetyl-CoA Molecule

The complete oxidation of $1\,\text{mol}$ of acetyl-CoA in the citric acid cycle yields $12\,\text{ATP}$ ($1\,\text{ATP}$ from substrate-level phosphorylation and $11\,\text{ATP}$ via oxidative phosphorylation).

Substrate-Level Phosphorylation in CAC

The direct synthesis of high-energy phosphate ($1\,\text{GTP} = 1\,\text{ATP}$) during the conversion of succinyl-CoA to succinate catalyzed by succinate thiokinase.

ATP Yield from Anaerobic Glycolysis

A net production of $2\,\text{ATP}$ per glucose molecule obtained exclusively by substrate-level phosphorylation in the absence of $\text{O}_2$.

ATP Yield from Complete Aerobic Glucose Oxidation

A total net production of $38\,\text{ATP}$ per mole of glucose ($4\,\text{ATP}$ by substrate-level phosphorylation and $34\,\text{ATP}$ by oxidative phosphorylation).

Allosteric Regulators of the Citric Acid Cycle

Cellular energy indicators: high ADP, AMP, and $\text{NAD}^+$ stimulate the cycle to increase energy output, whereas high ATP and NADH inhibit it.

Hormonal Non-Regulation of CAC

The regulatory feature stating that the citric acid cycle is not directly controlled by insulin or other hormones, but rather by cellular energy charge.

Biosynthetic Roles of Succinyl-CoA

A citric acid cycle intermediate that provides precursor molecules for ketolysis (ketone body oxidation), heme synthesis (for hemoglobin in RBCs), and detoxification of toxic compounds and drugs.