AEROBIC METABOLISM
Overview of Aerobic Metabolism.
Aerobic (oxygen-using) metabolism extracts energy from carbohydrate sources, fatty acids and amino acids. While glycolysis yields two moles of ATP from one mole of glucose, full oxidation of glucose by aerobic respiration produces ~30 moles of ATP.
Aerobic metabolism occurs in three phases. First, carbohydrates are oxidized to CO2, producing the energy-rich molecules NADH and FADH2. Electrons from NADH and FADH2 are then passed along the electron transport chain to the terminal electron acceptor O2. The free energy released in electron transport is captured by coupling it to the export of protons across the mitochondrial inner membrane. Finally, the free energy of the electrochemical proton gradient is used to synthesize ATP from ADP, Pi and H+, and to export ATP from the mitochondria.
Many catabolic pathways (carbohydrate, amino acid, fatty acid, and ketone body) converge at the TCA cycle. Many anabolic pathways depart from the TCA cycle, including synthesis of fatty acids, amino acids, purine bases, heme, cholesterol, steroid hormones and ketone bodies. The TCA cycle provides carbon skeletons in a variety of different oxidation states for these biochemical processes.
Aerobic (oxygen-using) metabolism extracts energy from carbohydrate sources, fatty acids and amino acids. While glycolysis yields two moles of ATP from one mole of glucose, full oxidation of glucose by aerobic respiration produces ~30 moles of ATP.
Aerobic metabolism occurs in three phases. First, carbohydrates are oxidized to CO2, producing the energy-rich molecules NADH and FADH2. Electrons from NADH and FADH2 are then passed along the electron transport chain to the terminal electron acceptor O2. The free energy released in electron transport is captured by coupling it to the export of protons across the mitochondrial inner membrane. Finally, the free energy of the electrochemical proton gradient is used to synthesize ATP from ADP, Pi and H+, and to export ATP from the mitochondria.
Many catabolic pathways (carbohydrate, amino acid, fatty acid, and ketone body) converge at the TCA cycle. Many anabolic pathways depart from the TCA cycle, including synthesis of fatty acids, amino acids, purine bases, heme, cholesterol, steroid hormones and ketone bodies. The TCA cycle provides carbon skeletons in a variety of different oxidation states for these biochemical processes.
Aerobic Metabolism in Eukaryotes Occurs in Mitochondria.
Mitochondria are oval organelles ~2 mM long and ~0.5 mM in diameter. They are present in most differentiated tissues, with the exception of mature erythrocytes, cornea and lens tissue. The outer membrane is permeable to metabolites because it contains many copies of the porin protein. The inner membrane is impermeable to polar metabolites. Specific transporters are utilized to pass small molecules across it.
The inner membrane contains the electron transport proteins and the F0F1 ATP synthase. Matrix proteins include pyruvate dehydrogenase, the TCA cycle enzymes, the enzymes of fatty acid catabolism, and the enzymes that catalyze the first steps of the urea cycle. The highly folded nature of the mitochondrial inner membrane results in a high ratio of membrane surface area to matrix volume, which allows rapid exchange of NADH between the soluble enzymes of the TCA cycle and the membrane bound electron transport machinery.
Protons are pumped out of the mitochondrial matrix and into the cytosol, producing a pH gradient of 1.5 pH units and a 140 millivolt electrostatic potential difference across the inner membrane. Mitochondria act as intracellular chemical reactors, and as chemical/electrical capacitors.
Oxidative Decarboxylation of Pyruvate:
The reaction catalyzed by the pyruvate dehydrogenase complex occurs in three steps, catalyzed by three different subunits of a multi-protein complex in the mitochondrial matrix.
1. Decarboxylation of an a-keto acid. The mechanism utilizes the catalytic cofactor thiamine pyrophosphate (TPP) to stabilize an acyl carbanion. TPP acts as an electron sink. The same mechanism is used by the enzyme a-ketoglutarate dehydrogenase (TCA cycle) and transketolase (pentose phosphate pathway). The acyl carbanion is oxidized to a thiolester by the intramolecular disulfide of lipoic acid. The thiolester represents a high energy bond (cf. the acyl enzyme intermediate of glyceraldehyde-3-phosphate dehydrogenase). Decarboxylation helps to drive the reaction forward. Both steps are catalyzed by the pyruvate decarboxylase or E1 subunit of the complex