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
Compartmentalization

Different organs

Gluconeogenesis

Fermentation
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
M4 isozyme
works better for
H4 (heart)
the forward rxn
(skeletal muscle H3M (heart & RBC)
needs NAD+).
H2M2 (brain & kidney)
H4 isozyme
works better for the HM3 (skeletal muscle)
back rxn (heart
uses lactate; takes M4 (skeletal muscle)
it back to
pyruvate).
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 B3)

Biological Electron Carriers: FADH2/FMNH2

From riboflavin (B2)

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 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
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 --> 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
Free Energy in the Cell
Free Energy in the Cell
High
Energy

Low
Energy
Example 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.