Catabolism and the Production of ATP (Chapter 2: pp. 88-102)

I. Overview: Three stages of oxidative breakdown of nutrient molecules (Figure 2-70 in powerpoint).

A. Stage 1: Breakdown of macromolecules to subunits: Digestion.

B. Stage 2: Breakdown of subunits of acetyl-CoA: Glycolysis and Pyruvate Dehydrogenase Complex. Beta-Oxidation of Fatty Acids

C. Stage 3: Oxidation of Acetyl-CoA to CO2 and H2O. Production of NADH and ATP. Takes place in mitochondria. Electron Transport and Oxidative Phosphorylation.

II. A. Glycolysis: 10 steps (Panel 2-8, Fig. 2-70 in book). Glucose + 2ATP + 2NAD+ 2 Pyruvates + 2 NADH + 4 ATP

1. 1st Five Stops: ATP energy is invested and energy content is rearranged as glucose is converted to 2 molecules of glyceraldehyde 3-phosphate.

2. Steps 6-7: 2 Glyceraldehyde 3-phosphates are oxidized and the energy released is used to synthesize 2 ATP (substrate level phosphorylation) and 2 NADH. The NAD+ can be regenerated for glycolysis by lactate dehydrogenase (anaerobic) or by electron shuttles (aerobic).

3. Steps 8-10: Energy is rearranged to create 2 high-energy molecules (PEP) which are used to synthesize 2 more ATPs. Two pyruvates are the final products of glycolysis.

B. Steps 6-7: Oxidation of Glyceraldehyde 3-Phosphate and the Formation of ATP and NADH (Figures 2-72 and 2-73).

III. The Oxidation of Pyruvate and Fatty Acids to Acetyl-CoA.

A. Pyruvate Dehydrogenase Complex in Matrix of Mitochondria: Pyruvate + NAD+ + Coenzyme A Acetyl CoA + COs + NADHThe Acetyl-CoA produced enters the citric acid cycle while the high-energy electrons enter the electron transport chain (Figure 2-79).

B. Beta-Oxidation of Fatty Acids to Acetyl-CoA. It is a 4-step cycle that takes place in matrix of mitochondria. Each turn of the cycle produces an acetyl CoA, and NADH, a FADH2, and a fatty acid shortened by 2 carbons. The Acetyl-CoAs produced can enter the citric acid cycle while the high-energy electrons enter the electron transport chain (Figure 2-81).

IV. Citric Acid Cycle (Panel 2-9 and Figure 2-82): Acetyl-CoA enters the citric acid cycle. 8 steps inside the mitochondria. For every acetyl-CoA that enters the cycle, 2 CO2 leave the cycle. 3 NADH, 1 FADH2, and 1 GTP are produced per turn of the cycle. Therefore, as 2 carbons are completely oxidized to 2 COs, much of the energy released is stored in high-energy electrons. Chemical bond energy is converted to high-energy electrons.

V. Electron Transport Chain and ATP Synthase: The high-energy electrons are donated to the electron transport chain, which is part of the inner membrane of the mitochondria. The electrons lose energy as they travel through a series of carriers to the final electron acceptor, O2. Much of this released energy is used to translocate protons across the inner membrane to the intermembrane space creating an electrochemical gradient. The energy in high-energy electrons is converted to gradient energy. The protons are allowed to reenter the mitochondria through ATP synthase, which uses the energy released to synthesize ATP from ADP and Pi. Electrochemical gradient energy is converted to chemical bond energy in the form of phosphoanhydride bonds. The whole process is called oxidative phosphorylation.

VI. Storage forms of Energy:

A. Glycogen: Glucose can be stored in glycogen granules, which are made of alpha 1,4 and alpha 1,6 linkages of glucose. When glucose is needed for metabolism it can be released from glycogen. Plants store glucose in starch granules, which have fewer alpha 1,6 branch points (Figure 2-75).

B. Fatty Acids: Fatty acids are stored in triacylglycerol (TAG). Three fatty acids are linked via ester bonds to a glycerol to form neutral fat. TAG molecules will form a lipid droplet. Lipases can hydrolyze the ester bonds to liberate the fatty acids for catabolism (Figs. 2-78 and 2-81).

VII. Nitrogen Cycle: Nucleotides and Amino Acids. We get most of our nitrogen from our diet in the form of protein and nucleic acids. Organic nitrogen passes from organism to organism so not much fixation of molecular nitrogen is needed. A few microorganisms are capable of fixing molecular nitrogen.

VIII. Organization and Regulation of Metabolism: Metabolic pathways do not go full speed all the time. Certain enzymes in each metabolic pathway are regulatory enzymes that set the speed of the pathway. These enzymes may be modulated by reversible phosphorylation (covalent modification) or by the concentration of certain metabolites (allosteric regulation). In metabolism there are branch points where a given metabolite can proceed into one of several pathways. The regulatory enzymes help determine how much of the metabolite will go into each pathway.