Principles of Biochemistry Exam 4

Aerobic Metabolism

In the presence of oxygen, pyruvate loses one molecule of CO2​, and the remaining two carbon atoms become linked to Coenzyme A (CoA) to form acetyl-CoA which then enters the citric acid cycle.

Anaerobic Glycolysis

Occurs in muscle tissue. In the absence of oxygen, pyruvate is reduced to lactate in a reaction catalyzed by lactate dehydrogenase (LDH). This pathway regenerates NAD+ from NADH, sustaining the continued oxidation of glyceraldehyde-3-phosphate in glycolysis.

Alcoholic Fermentation

Occurs in organisms such as yeast. In the absence of oxygen, pyruvate is first decarboxylated (loses CO2​) to form acetaldehyde, catalyzed by pyruvate decarboxylase (which requires TPP and Mg²⁺). Acetaldehyde is then reduced to ethanol by alcohol dehydrogenase. This pathway regenerates NAD+ from NADH, sustaining the continued oxidation of glyceraldehyde-3-phosphate in glycolysis.

Where does the Citric Acid Cycle take place?

Occurs primarily in the mitochondrial matrix in eukaryotes

Citric Acid Cycle Step 1

Acetyl-CoA + Oxaloacetate + H2​O → Citrate + CoA-SH. Reaction is performed by Citrate synthase. The energy released by the cleavage of the thioester bond in acetyl-CoA drives this highly exergonic step.

Citric Acid Cycle Step 2

Citrate → Isocitrate. Reaction is performed by Aconitase.

Citric Acid Cycle Step 3

Isocitrate + NAD+ → α-Ketoglutarate + NADH + CO2​ + H+. Reaction is performed by Isocitrate dehydrogenase.

Citric Acid Cycle Step 4

α-Ketoglutarate + NAD+ + CoA-SH → Succinyl-CoA + NADH + CO2​ + H+. Reaction is performed by α-Ketoglutarate dehydrogenase

Citric Acid Cycle Step 5

Succinyl-CoA + GDP + Pi​ → Succinate + GTP + CoA-SH. Reaction is performed by Succinyl-CoA synthetase.

Citric Acid Cycle Step 6

Succinate + FAD → Fumarate + FADH_2​. Reaction is performed by Succinate dehydrogenase.

Citric Acid Cycle Step 7

Fumarate + H2​O → L-Malate. Reaction is performed by Fumarase.

Citric Acid Cycle Step 8

L-Malate + NAD+ → Oxaloacetate + NADH + H+. Reaction is performed by Malate dehydrogenase.

Products of the Citric Acid Cycle

Per 1 Acetyl-CoA = 3 NAD+ are reduced to NADH (Steps 3, 4, and 8), 1 FAD is reduced to FADH_2​ (Step 6), and 2 CO₂​ are released (Steps 3 and 4). The cycle also yields 1 GTP (Step 5).

Citric Acid Cycle Inhibitors

ATP and NADH signal high energy charge and typically inhibit the rate-limiting steps (1, 3, 5). Succinyl-CoA is also an inhibitor

Citric Acid Cycle Activators

ADP and NAD+ signal low energy charge and typically activate the steps

Citric Acid Cycle Control Points

Regulation occurs at the pyruvate dehydrogenase reaction (pyruvate entry) and at three points within the cycle: citrate synthase (Step 1), isocitrate dehydrogenase (Step 3), and a-ketoglutarate dehydrogenase complex (Step 4).

Where does the Electron Transport Chain take place?

Complexes are located in the inner mitochondrial membrane

Flow of Electrons in the ETC

Electrons from NADH and FADH₂ move spontaneously toward carriers with more positive reduction potentials.

Chemiosmotic Coupling

The energy released during electron transport is used to pump protons (H+) from the mitochondrial matrix into the intermembrane space, creating a proton gradient (or pH gradient).

ATP Synthase

This gradient represents stored potential energy. Protons flow back into the matrix through ion channels in the F_0​ component. This proton flux drives the F1​ component to synthesize ATP.

Electron Transport Chain ATP Yield (Total)

Each NADH (3) yields 2.5 ATP, and each FADH_2​ (1) yields 1.5 ATP when reoxidized.

Glycerol-Phosphate Shuttle

Found in muscle and brain, transfers electrons to FAD (producing FADH2​ inside the matrix), yielding 1.5 ATP per cytosolic NADH.

Malate-Aspartate Shuttle

Found in heart and liver, transfers electrons to NAD+ (producing NADH inside the matrix), yielding 2.5 ATP per cytosolic NADH.

Net Total ATP from Glucose

Complete aerobic oxidation of one molecule yields 30 or 32 ATP, depending on which shuttle mechanism is utilized by the cell