Biochemistry. Metabolism

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1 Biochemistry Metabolism GABA shunt Glyoxylate cycle Respiratory chain Gerhild van Echten-Deckert Tel

2 Reactions of the citric acid cycle Berg, Tymoczko, Stryer: Biochemistry

3 The GABA-Shunt SuccinylCoA synthethase Biochemie u. Pathobiochemie. Löffler & Petrides

4 The glyoxylate cycle a short circuit from isocitrate to malate - net conversion of 2 AcCoA to succinate in the glyoxysome, which can be converted to malate in the mitochondrion for use in gluconeogenesis in the cytosol 2AcetylCoA+NAD + +2 H 2 O Succinate+2CoA+2NADH+H +

5 - Only in plants (glyoxisomes) -Enables seeds to convert fats into sugars Malate can continue in the TCA making the glyoxylate cycle anaplerotic

6 Electron micrograph of a germinating cucumber seed

7 Citric acid cycle is the common final oxidative path linking catabolism to respiratory chain Stage 1: Acetyl-CoA production Stage 2: Acetyl-CoA oxidation Stage 3: Electron transfer and oxidative phosphorylation

acid cycle, -oxidation of fatty acids mitochondrial

8 Inner membrane: enzymes of the respiratory chain, transporters Matrix: catabolic enzymes : citric acid cycle, -oxidation of fatty acids mitochondrial DNA and RNA, ribosomes Function: energy production (ATP)

9 Generation of reducing equivalents during glucose degradation and their utilization in the oxidative phosphorylation. 1/2O 2 + NADH + H + H 2 O + NAD + G o = -218 kj/mol G o = - n x F x E o = - 2 x 96,5 x 1.14

10 Measurement of the redox potential e - Sample half-cell Standard half-cell X + H + = X + ½ H 2 X = X + e H + + e - = ½ H 2

11 The mitochondrial respiratory chain (an electron transport system) Green: mobile components Red: respiratory inhibitors Blue: points where sufficient energy is harvested to synthesize ATP

12 The path of e - and p + along the mitochondrial respiratory chain Lodish et al. Molecular Biology of the Cell

14 Coenzym Q: a collecting pool for electrons derived from : Complex I Complex II (succinate-dh) Glycerol 3-phosphate-DH (see below) AcylCoA-DH ( -oxidation of fatty acids) Dihydroorotate-DH (pyrimidine-biosynthesis)

15 The malate-aspartate-shuttle enables the shift of cytosolic NADH into the mitochondria

16 The oxidation states of: a.) FMN b.)coq Both co-enzymes form stabile semiquinones (radicals)

17 Spatial structure of protein-bound iron-sulfur centres

18 Prosthetic groups of cytochromes contain heme-bound iron

19 Structure and topology of F 1 /F 0 -ATPase Eukaryotes The proton-motive force drives p + back into the matrix providing energy for ATP formation catalyzed by F 1 /F 0 -ATP-ase.

20 Experimental evidence for the rotation of the c ring in E. coli F 1 /F 0 -ATPase

21 Schematic diagram of the action of the E. coli F 1 /F 0 -ATPase

22 ATP synthase: conversion of electro-chemical energy into mechanical energy Berg, Tymoczko, Stryer: Biochemistry

23 Proton path through the F 0 -unit of ATP-synthase Berg, Tymoczko, Stryer: Biochemistry

24 Mechanism of ATP synthase Energy-dependent conformational changes: O = open, T = tight, L = loose

25 ATP yield from glucose degradation: Anaerobic: 2 ATP Aerobic: 30 ATP from 10 NADH 4 ATP from 2 FADH 2 ATP corresp. 2 GTP 2 ATP from glycolysis 38 ATP Biochemistry. Voet & Voet

26 Proton-transporting ionophores uncouple oxidative phosphorylation Biochemistry. Voet & Voet

27 Heat generation by uncoupled brown fat mitochondria Thermogenin (UCP, uncoupling protein): GDP: inhibitor of UCP-1

28 The topology of the F 0 /F 1 -ATPase in membranes and the direction of proton flow in bacteria, mitochondria, chloroplasts

29 The Cori cycle Glucose-alanine cycle

30 Lactic Acidosis Elevated concentrations of lactate in the plasma, termed lactic acidosis, occur when there is a collapse of the circulatory system, such as in myocardial infarction, pulmonary embolism, and uncontrolled hemorrhage, or when an individual is in shock. Failure to bring adequate amounts of oxygen to the tissues results in impaired oxidative phosphorylation and decreased ATP synthesis. To survive, the cells use anaerobic glycolysis as a backup system for generating ATP, producing lactic acid as the end product. Production of even meager amounts of ATP may be life-saving during the period required to reestablish adequate blood flow to the tissues. The excess oxygen required to recover from a period when the availability of oxygen has been inadequate is termed the oxygen debt.

Chapter 9. Cellular Respiration: Harvesting Chemical Energy

Chapter 9. Cellular Respiration: Harvesting Chemical Energy Chapter 9 Cellular Respiration: Harvesting Chemical Energy Living cells require energy from outside sources Energy flows into an ecosystem as sunlight and leaves as heat Photosynthesis generates O 2 and