KE7001 Biochemistry Lectures

Fatty acid metabolism

Reading material: Stryer, Chapter 22

Abstract: Fatty acids have major physiologic roles, such as being building blocks of phospholipids and glycolipids (components of cell membranes), precursors of hormones and intracellular messengers, fuel molecules, etc. Because fatty acids are highly reduced, yielding 9 kcal/g after complete oxidation, they give twice as much energy as carbohydrates and proteins. Fatty acids can originate either in the diet or from de novo synthesis in the cytosol of cells.

Fatty acid synthesis requires C atoms (as acetyl-CoA) and reducing power as NADPH. Acetyl groups are translocated from mitochondria to the cytosol as citrate (though in ruminants acetate from the rumen is the main precursor of cytosolic acetyl-CoA). Sources of NADPH are: the pentose phosphate pathway, the malate dehydrogenase cycle. Fatty acid synthesis starts with the carboxylation of acetyl CoA to malonyl-CoA catalyzed by acetyl-CoA carboxylase, followed by the elongation cycle catalyzed by the enzyme system called fatty acid synthase. The elongation cycle continues until C₁₆-acyl-ACP is formed. Further elongation and unsaturation of fatty acids are carried out by accessory enzyme systems on the cytosolic face of the endoplasmic reticulum membrane.

Fatty acid degradation takes a different pathway than synthesis. It occurs in mitochondria, after translocation of the fatty acids from the cytosol by carnitine. In the mitochondria, fatty acid degradation proceeds primarily by beta-oxidation that results in a stepwise removal of two carbons as acetyl-CoA from the carboxyl end of the acid, and in generation of FADH₂ and NADH. Acetyl-CoA enters the citric acid cycle and generates three molecules of NADH and one of FADH₂. Therefore, the complete oxidation of palmitate yields 106 ATP.

In fasting or diabetes, oxaloacetate is consumed to form glucose and can therefore not condense with acetyl-CoA. Under these conditions acetyl-CoA is transformed to ketone bodies mainly in the liver.

Links:
Stryer: Overview of Carbohydrate and Fatty Acid Metabolism (Conceptual insight)
Stryer: Chapter 22 Living figures (Use Netscape/Chime)

To lecture index