1. BC 368 Biochemistry of the Cell II Bioenergetics Chapter 13 and Intro to Part II March 4, 2014

2.  Sum total of all chemical reactions in the cell Overview of Metabolism

3.  Sum total of all chemical reactions in the cell Overview of Metabolism

4.  Molecular rationale of each pathway?  Key rxns?  Regulation?  Effect of mutations?

5. Two Phases of Metabolism Breaking down Building up

6. Two Phases of Metabolism

7.  Universal pathways and metabolites  Catabolic pathways may converge to a common intermediate.  Anabolic pathways may diverge from a common precursor. Metabolic Strategies

9.  Compartmentalization allows control, particularly of opposing pathways. Metabolic Strategies

10.  Different organelles Compartmentalization

11.  Different organs Compartmentalization Gluconeogenesis Fermentation

12.  Compartmentalization allows control, particularly of opposing pathways.  Pathways are controlled at a few key steps, usually the irreversible ones. Metabolic Strategies

13. Enzyme regulation: allosteric regulation  Binding of one ligand (noncovalently) influences the binding of another ligand to a different protein site.  Allosteric enzymes are oligomers.

14. Enzyme regulation: feedback inhibition Feedforward activation

15. Enzyme regulation: covalent modification  In response to a hormonal signal, an enzyme covalently modifies the regulated enzyme.  One type of covalent modification is phosphorylation, which can turn on or turn off a target enzyme.

16. Enzyme regulation: isozymes  Different forms of the same enzyme with different kinetic/regulatory properties. Often found in different tissues or at different developmental stages.  Example: lactate dehydrogenase Rxn catalyzed 4° structure: tetramer of M and H subunits

17. Isozymes H 4 (heart) H 3 M (heart & RBC) H 2 M 2 (brain & kidney) HM 3 (skeletal muscle) M 4 (skeletal muscle)  M 4 isozyme works better for the forward rxn (skeletal muscle needs NAD + ).  H 4 isozyme works better for the back rxn (heart uses lactate; takes it back to pyruvate). Pyruvate + NADH  Lactate + NAD +

18.  Compartmentalization  Pathways are controlled at a few key steps, usually the irreversible ones. Metabolic Strategies  Opposing pathways (anabolic vs. catabolic) are not simply the reverse of each other, although they may share many reactions.

19. 3 bypasses  Glycolysis: glucose  2 pyruvate  Gluconeogenesis: 2 pyruvate  glucose Glycolysis vs. Gluconeogenesis Glycolysis vs. Gluconeogenesis

20.  Cells use a universal set of electron carriers. Metabolic Strategies

21. Biological Electron Carriers: NADH/NADPH From niacin (vitamin B3)

22. From riboflavin (B2) Biological Electron Carriers: FADH 2 /FMNH 2

23. Niacin Deficiency  Niacin or tryptophan deficiency can lead to pellagra.

24. Niacin Deficiency  Niacin or tryptophan deficiency can lead to pellagra.  The four D’s: dermatitis, dementia, diarrhea, and death.

25. You are an internal medicine physician in South Dakota and a 56-year-old patient is brought in by his wife because of a newly- onset rapidly progressive dementia. He also has been suffering recently from diarrhea and dry skin on his face, neck, and back of his hands. For the patient to develop this disease, his diet must be deficient in which of these essential amino acids? 1) Leucine 2) Lysine 3) Phenylalanine 4) Tryptophan 5) Threonine 6) Arginine 1) Leucine 2) Lysine 3) Phenylalanine 4) Tryptophan 5) Threonine 6) Arginine

26.  Cells use a universal set of electron carriers.  Cells use ATP as the universal energy currency. Metabolic Strategies

27. In-class problem Under what conditions will the following reaction of glycolysis be spontaneous? Fructose 1,6-bisphosphate --> G3P + DHAP  G'  = 23.8 kJ/mol a)Under standard conditions b)Under no conditions c)When [G3P] and [DHAP] >> [F1,6-BP] d)When [F1,6-BP] >> [G3P] and [DHAP] e)Only when coupled to an exergonic reaction

28. Free Energy in the Cell

30. High Energy Low Energy

32. Example of phosphoryl transfer  G hydrolysis = -43.1 kJ/mol  G hydrolysis = -30.5 kJ/mol  The PCr in a contracting muscle runs out in about 10 seconds.