Overview

• The oxidation of long chain fatty acids to acetyl CoA serves as a central energy yielding pathway in many organisms and tissues.

  • Provides as much as 80 percent of the energetic needs in the mammalian heart and liver
  • Provides more than 40 percent of the daily energy requirement
• Electrons removed from fatty acids during oxidation pass through the respiratory chain, driving ATP synthesis.
• Acetyl CoA produced from the fatty acids may be completely oxidized to CO2 in the citric acid cycle.
• Beta oxidation is the oxidation of the fatty acyl group at the C-3, or beta position, hence the name

  • Occurs after the carboxyl group at C-1 is activated by attachment to coenzyme A
• Metabolites of diverse origin funnel into a few central pathways.
• Fatty acid catabolism and glycolysis convert quite different starting materials into the same product (acetyl CoA). The electrons from the oxidative reactions of these pathways and of the citric acid cycle are carried by common cofactors (NAD and FAD) to the mitochondrial respiratory chain leading to oxygen, providing energy for ATP synthesis by oxidative phosphorylation.
• Evolution select for chemical mechanisms that make useful reactions more energetically favorable, and those some mechanisms are used in different pathways.
• In the breakdown of fatty acids, we see the activation of a carboxylic acid by its conversion to a thioester. To break C-C conds in the long chain of relatively inert -CH2-CH2- groups in fatty acids, a carbonyl group is created adjacent to the -CH2- group.
• Allosteric mechanisms and posttranslational regulation (protein phosphorylation) coordinate metabolic processes within a cell. Hormones and growth factors coordinate metabolic activities among tissues and organs.
• Reciprocal regulation of catabolic and anabolic pathways prevents the inefficiency of futile cycling.
• When a process lacks a critical component- an enzyme, a cofactor, or a regulatory agent- the resulting loss of homeostasis may cause disease across a spectrum of severity. Defects in fatty acid breakdown are no exception.
• The liver plays a unique role in whole body metabolism. When glucose is unavailable, the liver makes glucose by gluconeogenesis and releases it to the blood for distribution to other tissues, including the brain. During starvation, the liver processes fatty acids into ketone bodies, which, unlike fatty acids, can cross the blood brain barrier and fuel the brain.