Transcript Concepts in Biochemistry 3/e

Metabolic interrelationship
Chapter 6:
Integration, Specialization, and Regulation of
Metabolism
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At this point, we’ll
consider how
organisms
arrange/organize the
metabolic symphony
to meet their energy
needs.
Discussion will
include how:
 Body maintains
energy balance
(homeostasis)
 It deals with
starvation
 It responds to the
loss of control from
diabetes mellitus
Table 24-2, p.666
Food pyramid
Fig. 24-2, p.668
Obesity
-Define as
weighing at least
20% more than
their ideal weight
- several
inventions:
artificial
sweeteners, fat
substitutes
- protein leptin
plays a role in the
control of obesity
- Has been
established in
mice
- in mice, leptin is
16kDa protein
that produced by
obesity (ob) gene
- mutation in this
gene will lead to
deficiency of
leptin
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Review of
metabolism
Glycolysis
Gluconeogene
sis
The pentose
phosphate
pathway
Β oxidation
and fatty acids
synthesis
Amino acids
degradation
and synthesis
The citric acid
cycle
Oxidative
phosphorylati
on
Glucose-6phosphate
Pyruvate
Acetyl-CoA
Oxaloacetate
Intermediates
that connect
pathways
Brain
Muscle
Liver
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The fate of G6P varies with metabolic
requirements – depends on the glucose demand
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G6P can be converted to glucose by glucose-6phosphatase (transport via bloodstream to the
peripheral organs)
G6P can be converted to glycogen – when body’s
demand for glucose is low
G6P can be converted to acetyl-CoA via glycolysis
and action of pyruvate dehydrogenase (this glucosederived acetyl-CoA used in the synthesis of f.acids)
G6P can be degraded via pentose phosphate pathway
(to generate NADPH required for f.acids biosynthesis
and liver’s many other biosynthetic functions)
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The liver can synthesize or degrade TAGs
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When metabolic fuel is needed, f.acids are degraded
to acetyl-CoA and then to ketone bodies (export via
bloodstream to the peripheral tissues)
When the demand is low, f.acids are used to
synthesize TAGs (secreted into the bloodstream as
VLDL for uptake by adipose tissue)
Amino acids are important metabolic fuel
 The liver degrades amino acids to a variety of
intermediates (begin with a.acid transamination to
yield α-keto acid, via urea cycle excreted urea)
 Glucogenic a.acid – converted to pyruvate / OAA
(TCA cycle intermediates)
 Ketogenic a.acid – converted to ketone bodies
Kidney
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Functions
: to filter out the waste
product urea from the
bloodstream
: to concentrate it for
excretion
: to recover important
metabolites (glucose)
: to maintain the blood
pH
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Overall reaction in
kidney: Glutamine →
α-ketoglutarate +
NH4+
During starvation, the
α-ketoglutarate enters
gluconeogenesis
(kidneys generate as
much as 50% of the
body’s glucose supply)
α-ketoglutarate :
converted to malate
(TCA cycle)
: pyruvate (oxidized to
CO2) or via OAA to PEP
: converted to glucose
via gluconeogenesis
Hormones reacts as the intercellular messengers
Hormones transported from the sites of their synthesis to
the sites of action by the bloodstream
Fig. 24-5, p.671
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Some typical
hormones:
- steroids
(estrogens,
androgens)
- polypeptides
(insulin and
endorphins)
- a.acid derivatives
(epinephrine and
norepinephrine)
Hormones help
maintaining
homeostasis (the
balance of biological
activities
Table 24-3, p.672
Control system
mechanism
Hormone releasing factor
Fig. 24-7, p.673
Fig. 24-8, p.674
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Second messenger e.g
cyclic AMP (cAMP)
p.676
Fig. 24-9a, p.675
Fig. 24-9b, p.675
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The effects of hormones triggered
the responses within the cell
There are three hormones play a
part in the regulation of CHO
metabolism
Epinephrine, insulin and glucagon
Epinephrine: acts on muscle tissue,
to raise level of glucose on
demand, when it binds to specific
receptors, it leads to increased
level of glucose in blood, increased
glycolysis in muscle cells and
increased breakdown of f.acid for
energy
p.681
Fig. 24-14, p.682
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Glucagon: acts on
liver, to increase
the availability of
glucose, when it
binds to specific
receptors, it leads
to increased level
of glucose in
blood.
Table 24-4, p.685
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During prolonged starvation or fasting, the brain slowly
adapts from the use of glucose as its soul fuel source to
the use of ketone bodies, shift the metabolic burden form
protein breakdown to fat breakdown
Diabetes mellitus is a disease in which insulin either not
secreted or doesn’t stimulate its target tissues → high
[glucose] in the blood and urine. Abnormally high
production of ketone bodies is one of the most dangerous
effects of uncontrolled diabetes
Dieting – to lose excess weight. Diet forced the body to
follow the same adjustment like starvation or fasting but
a more moderate or controllable pace. Dieting is not free
of problems, therefore it is advisable to undergo diet
under supervision of physician or nutritionist.