bc 368 biochemistry of the cell ii bioenergetics chapter 13 and intro to part ii march 4, 2014
TRANSCRIPT
BC 368Biochemistry of the Cell II
BC 368Biochemistry of the Cell II
BioenergeticsChapter 13 and Intro to Part II
March 4, 2014
Sum total of all chemical reactions in the cell
Overview of MetabolismOverview of Metabolism
Sum total of all chemical reactions in the cell
Overview of MetabolismOverview of Metabolism
Overview of MetabolismOverview of Metabolism
Molecular rationale of each pathway?
Key rxns?
Regulation?
Effect of mutations?
Two Phases of MetabolismTwo Phases of Metabolism
Breaking down
Building up
Two Phases of MetabolismTwo Phases of Metabolism
Universal pathways and metabolites
Catabolic pathways may converge to a common intermediate.
Anabolic pathways may diverge from a common precursor.
Metabolic StrategiesMetabolic Strategies
Compartmentalization allows control, particularly of opposing pathways.
Metabolic StrategiesMetabolic Strategies
Different organelles
CompartmentalizationCompartmentalization
Different organs
CompartmentalizationCompartmentalization
Compartmentalization allows control, particularly of opposing pathways.
Pathways are controlled at a few key steps, usually the irreversible ones.
Metabolic StrategiesMetabolic Strategies
Enzyme regulation: allosteric regulationEnzyme 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 inhibitionEnzyme regulation: feedback inhibition
Feedforward activation
Enzyme regulation: covalent modificationEnzyme 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: isozymesEnzyme regulation: isozymesDifferent 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
IsozymesIsozymes
H4 (heart)
H3M (heart & RBC)
H2M2 (brain & kidney)
HM3 (skeletal muscle)
M4 (skeletal muscle)
M4 isozyme works better for the forward rxn (skeletal muscle needs NAD+).
H4 isozyme works better for the back rxn (heart uses lactate; takes it back to pyruvate).
Pyruvate + NADH Lactate + NAD+
Compartmentalization
Pathways are controlled at a few key steps, usually the irreversible ones.
Metabolic StrategiesMetabolic Strategies
Opposing pathways (anabolic vs. catabolic) are not simply the reverse of each other, although they may share many reactions.
3 bypasses
Glycolysis:
glucose 2 pyruvate
Gluconeogenesis:
2 pyruvate glucose
Glycolysis vs.GluconeogenesisGlycolysis vs.Gluconeogenesis
Cells use a universal set of electron carriers.
Metabolic StrategiesMetabolic Strategies
Biological Electron Carriers: NADH/NADPHBiological Electron Carriers: NADH/NADPH
From niacin (vitamin B3)
From riboflavin (B2)
Biological Electron Carriers: FADH2/FMNH2Biological Electron Carriers: FADH2/FMNH2
Niacin DeficiencyNiacin Deficiency
Niacin or tryptophan deficiency can lead to pellagra.
Niacin DeficiencyNiacin 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 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?
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) Leucine2) Lysine3) Phenylalanine4) Tryptophan 5) Threonine6) Arginine
1) Leucine2) Lysine3) Phenylalanine4) Tryptophan 5) Threonine6) Arginine
Cells use a universal set of electron carriers.
Cells use ATP as the universal energy currency.
Metabolic StrategiesMetabolic Strategies
In-class problem
Under what conditions will the following reaction of glycolysis be spontaneous?
Fructose 1,6-bisphosphate --> G3P + DHAP
G' = 23.8 kJ/mola) 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
Free Energy in the CellFree Energy in the Cell
Free Energy in the CellFree Energy in the Cell
High Energy
Low Energy
Example of phosphoryl transferExample of phosphoryl transfer
Ghydrolysis= -43.1 kJ/mol
Ghydrolysis= -30.5 kJ/mol
The PCr in a contracting muscle runs out in about 10 seconds.