Biochemistry is fun!!! La Bioquímica es divertida!!!

1. Biochemistry is fun!!!La Bioquímica es divertida!!!

2. Pyruvate GTP  ATP (substrate level phosphorylation) Citric Acid Cycle (CAC) “Kreb Cycle” Tricarboxylic Acid Cycle 2/3 of O2 consumption needed for oxidation of Acetyl CoA  CO2 • Occurs exclusively in the • mitochondrion (matrix) • OAA acts as carrier or acceptor • of acetyl CoA units – is regenerated • “Burns” acetyl CoA to CO2 – during • this oxidation eˉs from acetyl CoA • are trapped in the form of: NADH Pyruvate Dehydrogenase Complex “links” glycolysis to CAC FADH + 2eˉ + 2eˉ + 2eˉ + 2eˉ

3. The Three Stages of Metabolism (H.A. Krebs)

4. The Krebs Cycle Citric Acid Cycle; The TCA Cycle • Pyruvate (actually the acetyl group) from glycolysis is degraded to CO2 • The acetyl group is formed in stage II of metabolism from carbohydrate and amino acid metabolism • 1GTP (ATP in bacteria) and 1 FADH2 is produced during one turn of the cycle • 3 NADH are produced during one turn of the cycle • NADH and FADH2 energize electron transport and oxidative phosphorylation • Eight reactions make up the Krebs cycle • If you are given the name of the enzyme, you should be able to draw the structure of the reactants and products • You may be given the names of all eight reactions and will be expected to reproduce the whole cycle

5. Overview of the Krebs Cycle: A Mitochondrial Process

6. Anatomy of the Mitochondrion • Which membrane is impermeable to protons and other ions? • Which membrane will allow for the transport of molecules up to a molecular weight of about 1000?

7. * Pyruvate transporter * Pyruvate mito matrix Coenzymes Thiamine Pyrophosphate (TTP) PyruvateDehydrogenaseComplex Cytoplasm Pyruvate Multimolecularaggregate 3 Enzymes 5 Coenzymes 5 Reactions Irreversible CoA contains the vitamin Pantothenic acid Links glycolysis to CAC Product Inhibition Mitochondrial matrix NAD+ FAD+ CoA Lipoic acid

8. CAC PDHDeficiency – results in CongenitalLacticAcidosis Pyruvate cannot enter the CAC and results in ↑ Lactic Acid Primarily affects the brain – neonatal death 3 Forms – psychomotor retardation √ Possible treatment is ketogenic diet: Low in CHO High in fats Produces ketone bodies as an alternate form of energy for the brain Arsenic Poisoning – Pyruvate Dehydrogenase –a-Ketoglutarate Dehydrogenase Both require lipoic acid as a cofactor Arsenite – Trivalent form of arsenic I° – Forms a stable complex with the thiol (-SH) group of Lipoic Acid II° – Glyceraldehyde 3-PO4 step forms complex with inorganic Pi thus prevents ATP formation in glycolysis Affects the brain – Death, neurologic problems

9. Skeletal muscle Contraction cAMP dependent √ Allosteric Regulation √ Allosteric Regulation

10. Carrier Fluorocitrate OAA Fluoroacetate ( ¯ ) Rat poison ADP (+) Aldo condensation The entrance of acetyl CoA does not ↑ or ↓ intermediates in the CAC Oxidative decarboxylation e¯ Irreversible (1) One of the rate limiting Rxs of the CAC ATP NADH¯

11. (¯) ATP. GTP Succinyl CoA NADH From oxidation of odd number FAs ADP GDP ATP Oxidative decarboxylation Very similar to the Pyruvate Dehydrogenase complex Irreversible (2) e¯ “Substrate Level Phosphorylation” Nucleoside Biphosphate Kinase Irreversible (3) e¯ Oxidation reaction Hydration reaction

12. e¯ ( 4 ) Reversible oxidation reaction

14. Regulation of the CAC Dependent on the energy state of the cell which is reflected by ratio [ADP] [Pi] [ATP] Summary This ratio determines the rate of oxidative phosphorylation Named “Respiratory Control” of energy production because oxidation and phosphorylation of ADP must occur simultaneously

16. Biochemistry is fun!!!La Bioquímica es divertida!!!