The Tricarboxylic Acid Cycle and Oxidative Phosphorylation

Hi, in this post we'll be discussing the TCA cycle and Oxidative Phosphorylation. I'll discuss where the TCA cycle and oxidative phosphylation occur and how much energy they produce. I'll also describe the location and function of the malate/aspartate and glycerol phosphate shuttles as well as how much energy they produce.

The Tricarboxylic Acid (TCA) Cycle

The TCA cycle, which is also known as the Citric Acid cycle or the Krebb's cycle, occurs in the mitochondria of a cell. This cycle is the final metabolic pathway for oxidising carbohydrates, lipids and proteins and plays a major role in gluconeogenesis, transamination, deamination and lipogenesis. The first enzymatic step in the TCA cycle is the conversion of Acetyl CoA to Citrate by the citrate synthetase enzyme. The cycle then continues as shown in the diagram below:

The TCA Cycle

The TCA cycle produces three NADH molecules and one NADH molecule produces 2.5ATP molecules. Thus 7.5 ATPs are produced from NADH. The TCA cycle also releases one FADH2 molecule, which releases 1.5 ATPs, in addition to one GTP molecule which results in the release of 1 ATP molecule through substrate level phosphorylation. Thus, 10 ATP molecules are produced per molecule of AcetylCoA. Since two molecules of Acetyl CoA are produced per molecule of glucose, 20ATP molecules are produced per glucose by the TCA cycle.   

Oxidative Phosphorylation

Oxidative phosphorylation occurs in the mitochondria of a cell and couples respiratory oxidation to ATP generation. It consists of the electron transport (ETC) chain which are located on the inner mitochondrial membrane.

The TCA cycle produces three NADH molecules and one NADH molecule yields 2.5ATP molecules via the electron transport chain. Thus 7.5 ATPs are produced from the production of NADH. The TCA cycle also releases one FADH2 molecule, which yields 1.5 ATPs through the ETC chain, in addition to one GTP molecule which results in the release of 1 ATP molecule through substrate level phosphorylation. Thus, 10 ATP molecules are produced per molecule of AcetylCoA.  

NADH Substrate Shuttles

The membrane of the mitochondria is impermeable to NADH and so cannot deliver its electrons to the electron transport chain. Because of this, NADH is transferred into the mitochondria by the glycerophosphate and malate/aspartate shuttles.

The Glycerol Phosphate Shuttle

In skeletal muscle, brain and other tissues, electrons are delivered from the NADH generated in the cytoplasm from glycolysis to the mitochondrial  electron transport chain by a shuttle that uses FAD as the electron acceptor. This is the glycerol phosphate shuttle. Dihydroxyacetone phosphate (DHAP) is reduced to glycerol-3-phosphate, which is transported into the mitochondrion. There, it is reoxidised to DHAP by an enzyme that uses FAD instead of NAD+ as its electron receptor. Because of this, these electrons bypass the first complex of the ETC, generating only 1.5ATP molecules instead of 2.5.

The Malate-Aspartate Shuttle

In the liver, kidney and heart cells, electrons from NADH produced in the cytoplasm from glycolysis are transferred into the mitochondrion via the malate-aspartate shuttle. NADH reduces oxaloacetate in the cytoplasm to malate which is transported into the mitochondrial matrix where it reduces NAD+ to NADH. Thus, the electrons from the NADH in the cytoplasm pass through the first three complexes of the ETC which generates 2.5 ATP.

ATP Yield

As discussed in a previous post, glycolysis produces 2 ATP molecules per molecule of glucose. During anaerobic respiration, this is all that is produced because the TCA cycle or oxidative phosphorylation aren't used.

During aerobic respiration, glycolysis produces 2ATP molecules per glucose. In addition, Pyruvate Dehydrogenase causes the release of 5ATP molecules per glucose. The TCA cycle produces 20ATP molecules per glucose. If the malate-aspartate shuttle is used, 2.5 ATP molecules are produced per NADH. Since glycolysis releases 2 NADH molecule, 5 ATP molecules are produced per glucose. This results in a total of 32 ATP molecules per glucose during aerobic respiration. If the glycerol phosphate shuttle is used, 30 ATP molecules will be produced. This is because the glycerol phosphate shuttle produces 1.5 ATPs per NADH and thus 3 molecules per glucose.  

That's it for this post, if you have any questions please feel free to ask :)