Lipid & Protein Metabolism

BREAKDOWN OF LIPID AND PROTEIN: Fat and protein metabolism only occur under aerobic conditions. Hydrogens from the citric acid cycle can be transferred from NADH and FADH2 to oxygen in the Electron Transport Chain to generate large amounts of ATP from these macronutrients.

3.1 Lipid metabolism under aerobic conditions (beta-oxidation)

ATP production from fat metabolism occurs exclusively in the mitochondrion. Lipids are stored as triacylglycerol droplets within muscle fibers in close proximity to the mitochondria. Triacylglycerols are also mobilized from adipose tissue stores (adipose cells). Triacylglycerol molecules are split into a glycerol molecule and three water-insoluble fatty acid molecules by the enzyme, lipase (equation 5):

Equation 5: Hydrolysis of triacylglycerol

This process stimulates the diffusion of fatty acids into the circulation. The free fatty acids (FFAs) are transported by albumin in the blood. The albumin-FFA complex releases FFAs for transport across the muscle plasma membrane by a protein-mediated carrier system. Once in the cytosol, large fatty acids bind to intramuscular proteins to enter the mitochondria (small and medium-chain fatty acids can diffuse freely). Once in the mitochondria, these fatty acids are broken down into acetyl-CoA via beta-oxidation (β-oxidation), resulting in the production of NADH and FADH2, which enter the electron transport chain to generate ATP via oxidative phosphorylation. Under aerobic conditions, each triacylglycerol molecule consisting of 3 fatty acid molecules, of 18 carbons each, results in the generation of 441 ATP from β-oxidation and citric acid cycle.

The glycerol molecule is converted into 3-phosphoglyceraldehyde, which degrades into pyruvate to form ATP through oxidative phosphorylation. The complete break down of a single glycerol molecule generates 19 ATP under aerobic conditions. Hence, each triacylglycerol molecule results in the production of 460 ATP (441 ATP from fatty acid metabolism + 19 ATP from glycerol metabolism). During exercise, increased levels of epinephrine, norepinephrine, glucagon, and growth hormone augment lipase activation (through cyclic AMP) and FFA mobilization from adipose tissue to serve as an energy source.

Figure 6. Dynamics of fat mobilization and fat use energy is released when triacylglycerols stored within the muscle fiber also degrade to glycerol and fatty acids. (for more detail, consult McArdle, Katch & Katch, figure 6.17)


3.2 Protein metabolism under aerobic conditions

Although protein breakdown is not a preferred source for energy, it can be used to resynthesize ATP under aerobic conditions. Protein metabolism occurs exclusively in the mitochondria; the first step constitutes the deamination of amino acids in the liver and skeletal muscle. The deaminated products are converted into pyruvate or acetyl-CoA depending on the identity of the amino acid, and some enter the citric acid cycle directly and generate hydrogens (NADH and FADH2) under aerobic conditions and ATP via the electron transport chain. Amino acids like threonine, serine, cysteine and glycine are glucogenic because are converted into pyruvate and then into acetyl-CoA, which then enters the citric acid cycle. Other amino acids like isoleucine, leucine, lysine, tyrosine, phenylalanine and tryptophan are ketogenic because they are transformed into acetyl-CoA to enter the citric acid cycle. The last class of amino acids, arginine, glutamine, tyrosine, among many others, enter the citric acid cycle directly. Glucogenic amino acids can contribute in gluconeogenesis (glucose synthesis) during prolonged exercise. While, ketogenic amino acids, cannot be used to synthesize glucose, rather they synthesize triacylglycerol.