BC 368 Biochemistry of the Cell II Bioenergetics
BC 368 Biochemistry of the Cell II Bioenergetics Chapter 13 and Intro to Part II March 4, 2014
Overview of Metabolism Sum total of all chemical reactions in the cell
Overview of Metabolism Sum total of all chemical reactions in the cell
Overview of Metabolism Molecular rationale of each pathway? Key rxns? Regulation? Effect of mutations?
Two Phases of Metabolism Breaking down Building up
Two Phases of Metabolism
Metabolic Strategies Universal pathways and metabolites Catabolic pathways may converge to a common intermediate. Anabolic pathways may diverge from a common precursor.
Metabolic Strategies Compartmentalization allows control, particularly of opposing pathways.
Compartmentalization Different organelles
Fermentation Different organs Gluconeogenesis Compartmentalization
Metabolic Strategies Compartmentalization allows control, particularly of opposing pathways. Pathways are controlled at a few key steps, usually the irreversible ones.
Enzyme regulation: allosteric regulation Binding of one ligand (noncovalently) influences the binding of another ligand to a different protein site. Allosteric enzymes are oligomers.
Enzyme regulation: feedback inhibition Feedforward activation
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.
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
Isozymes 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). H 4 (heart) H 3 M (heart & RBC) H 2 M 2 (brain & kidney) HM 3 (skeletal muscle) M 4 (skeletal muscle) Pyruvate + NADH Lactate + NAD+
Metabolic Strategies Compartmentalization Pathways are controlled at a few key steps, usually the irreversible ones. Opposing pathways (anabolic vs. catabolic) are not simply the reverse of each other, although they may share many reactions.
Glycolysis vs. Gluconeogenesis Glycolysis: glucose 2 pyruvate Gluconeogenesis: 2 pyruvate glucose 3 bypasses
Metabolic Strategies Cells use a universal set of electron carriers.
Biological Electron Carriers: NADH/NADPH From niacin (vitamin B 3)
Biological Electron Carriers: FADH 2/FMNH 2 From riboflavin (B 2)
Niacin Deficiency Niacin or tryptophan deficiency can lead to pellagra.
Niacin Deficiency Niacin or tryptophan deficiency can lead to pellagra. The four D’s: dermatitis, dementia, diarrhea, and death.
You are an internal medicine physician in South Dakota and a 56 -year-old patient is brought in by his wife because of a newlyonset 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) 2) 3) 4) 5) 6) Leucine Lysine Phenylalanine Tryptophan Threonine Arginine
Metabolic Strategies Cells use a universal set of electron carriers. Cells use ATP as the universal energy currency.
In-class problem Under what conditions will the following reaction of glycolysis be spontaneous? Fructose 1, 6 -bisphosphate --> G 3 P + DHAP G' = 23. 8 k. J/mol a) Under standard conditions b) Under no conditions c) When [G 3 P] and [DHAP] >> [F 1, 6 -BP] d) When [F 1, 6 -BP] >> [G 3 P] and [DHAP] e) Only when coupled to an exergonic reaction
Free Energy in the Cell
Free Energy in the Cell
High Energy Low Energy
Example of phosphoryl transfer Ghydrolysis= -43. 1 k. J/mol Ghydrolysis= -30. 5 k. J/mol The PCr in a contracting muscle runs out in about 10 seconds.
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