bc 368 biochemistry of the cell ii bioenergetics chapter 13 and intro to part ii march 4, 2014

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.