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Krebs cycle. hexose kinase. phosphofructokinase *. aldolase triose phosphate isomerase. phosphogyceraldehyde dehydrogenase. phosphoglycerate kinase. pyruvate kinase *. Lactate (or ethanol + CO 2 ). NAD+ NADPH. To TCA cycle.
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hexose kinase phosphofructokinase * aldolase triose phosphate isomerase phosphogyceraldehyde dehydrogenase phosphoglycerate kinase pyruvate kinase * Lactate (or ethanol + CO2) NAD+ NADPH
Glycolysis occurs in the cytosol of cells. Pyruvate enters the mitochondrion to be metabolized further. Mitochondrial Compartments: • The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle,andother pathways, e.g., fatty acid oxidation & amino acid metabolism. • The outer membrane contains large VDAC channels, similar to bacterial porin channels, making the outer membrane leaky to ions & small molecules.
The innermembrane is the major permeability barrier of the mitochondrion. It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix. It is highly convoluted, with infoldings called cristae. Embedded in the inner membrane are constituents of the respiratory chain and ATP Synthase.
Pyruvate (3 C) NADH +CO2 NAD+ Acetyl Co A (2C) Oxaloacetate (4C) Citrate (6C) NADH +CO2 NAD+ NAD+ NADH a Ketoglutarate (5C) Malate NADH +CO2 CoA + NAD+ HOH Succinyl CoA (4C) Fumarate GTP +CoA GDP FAD FADH2 Succinate
Pyruvate Dehydrogenase, catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA.
Acetyl CoA functions as: • input to Krebs Cycle, where the acetate moiety is further degraded to CO2. • donor of acetate for synthesis of fatty acids, ketone bodies, & cholesterol.
3 ATP 3 ATP 3 ATP 3 ATP 1 ATP 2 ATP
Pyruvate (3 C) NADH +CO2 NAD+ Acetyl Co A (2C) Oxaloacetate (4C) Citrate (6C) NADH +CO2 NAD+ NAD+ NADH a Ketoglutarate (5C) Malate NADH +CO2 CoA + NAD+ HOH Succinyl CoA (4C) Fumarate GTP +CoA GDP FAD FADH2 Succinate
Scorecard: 2 ATP/glucose anaeobic gycolysis In addition, aerobically we get ~6 ATP from glycolysis NADH ~6 ATP from pyruvate dehydrogenase NADH ~18 ATP from TCA cycle NADH ~4 ATP from TCA cycle FADH 2 ATP from TCA cycle GTP So: aerobic metabolism ‘classically’ adds ~36 ATP, giving 38 altogether. As I’ll make clear, a bit less than this is made in reality.
Respiration • Glycolysis and the TCA cycle produce NADH, FADH2 and ATP (via GTP) as primary products, CO2 as a byproduct • Most of the ATP is made by transfering electrons from NADH and FADH2 to oxygen, forming water • This is done in the inner membranes of mitochondia and is called respiration
Mitchell’s Chemiosmotic Loop 2H+ B AH2 A C Outside (P Side) 2e- 2e- 2e- 2H+- Inside (N Side)