Principles of Biochemistry

3.6.2 Oxidative phosphorylation

The enzymes of the citric acid cycle, except for the ∝ -ketoglutarate and succinate dehydrogenase, are also found outside the mitochondria. As a result of oxidations catalyzed by dehydrogenase enzymes of the citric acid cycle, three molecules of NADH and one molecule of FADH 2 are produced for each molecule of acety1-CoA catabolized in one revolution of the cycle. These reducing equivalents are transferred to the respiratory chain in the inner mitochondrial membrane.

Respiratory chain and ATP production

    Pyruvate       ADP+Pi→ATP  ADP+Pi→ATP                        ADP+Pi→ATP

    Isocitrate                ↑             ↑                         ↑                       ∝ketoglutarate→NAD→FMN→CoQ→Cytb→CytC₁→CytC→Cyta→ Cyta_3.

    Malate

During passage along the respiratory chain, reducing equivalents from each NADH generate three high- energy phosphate bonds by the esterification of ADP to ATP in the process of oxidative phosphorylation. However, FADH 2 produces only two high- energy phosphate bonds because it transfers its reducing power to Co Q, by passing the first site for oxidative phosphorylation in the respiratory chain. A further high-energy phosphate is generated at the level of the cycle itself (i.e., at substrate level) during the conversion of succiny1 -CoA to succinate. Thus, 12 ATP molecules are generated for each turn of the cycle

ATP Production from glucose

One molecule of glucose is converted to 2 molecules of pyruvate by glycolysis and thepyruvate is further converted to acetyl CoA by pyruvate dehydrogenase before entering into citric acid cycle. During this process two more molecules of NADH are available for oxidation by the electron transport cycle reoxidation route to yield 6 ATP molecules. During the conversion of glucose to pyruvate two more molecules of ATP are available through substrate-linked phosphorylation. Thus the total number of ATP produced by the aerobic oxidation of glucose to carbon dioxide and water is 38(12+3=15x2 30+8=38) ATP molecule per each glucose molecule. Citric acid cycle intermediates are used for other metabolic purposes.

• It is an amphibolic pathway.
• It functions not only in the oxidative degradation of carbohydrates, fatty acids and amino acids but also as a source of precursors for other metabolic pathways.

 ATP production in mitochondria

 

Name of enzyme	Reaction Catalyzed	ATP molecules formed
Isocitrate dehydrogenase	Respiratory chain oxidation of NADH +H+	3
α-Ketoglutrate dehydrogenase	Respiratory chain oxidation of NADH +H+3	3
Succinate thiokinase	Phosphorylation at substrate level	1
Succinate dehydrogenase	Respiratory chain oxidation of FADH2	2
Malate dehydrogenase	Respiratory chain oxidation of NADH +H+	3
	Net	12