Feed-Fast Cycle
CONNECTION OF PATHWAYS
1.
ATP is the universal currency of energy
2.
ATP is generated by oxidation of glucose, fatty acids, and amino acids ; common
intermediate -> acetyl CoA ; electron carrier -> NADH and FADH2
3.
NADPH is major electron donor in reductive biosynthesis
4.
Biomolecules are constructed from a small set of building blocks
5.
Synthesis and degradation pathways almost always separated -> Compartmentation !!!
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METABOLIC PROFILE OF ORGANS
3
THE LIVER AS
CENTRAL PLAYER
• Blood from intestine
travels
via
hepatic
portal to liver 1st
• Liver ideally placed
to
regulate
fuel
Hepatic Artery
passage elsewhere
KEY JUNCTIONS BETWEEN PATHWAYS
5
FIVE PHASES OF GLUCOSE
HOMEOSTASIS
• Absorptive, post-absorptive, and early
starvation occur sequentially over ~2
days.
• Intermediate, and prolonged starvation
are over 38 subsequent days and beyond
POSTABSORPTIVE STATE
INSULIN SECRETION –STIMULATED BY GLUCOSE UPTAKE
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POSTABSORPTIVE STATE -> AFTER A MEAL
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METABOLIC PROFILE OF ADIPOSITE TISSUE
Triacylglycerols are stored in
tissue
->
enormous
reservoir
of
metabolic fuel
-> needs glucose to synthesis
TAG;
-> glucose level determines if
fatty acids are released into
blood
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METABOLIC PROFILE OF MUSCLES
Major fuels are glucose, fatty acids, and
ketone bodies
-> has a large storage of glycogen
-> glucose is preferred fuel for burst of
activity
-> production of lactate (anaerobe)
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METABOLIC PROFILE OF BRAIN
Glucose is fuel for human brain
-> ketone bodies can replace glucose
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MOBILIZATION AT STARVATION
Also at not
treated
diabetes
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EARLY FASTING STATE
Blood-glucose level drops after several hours after the meal
- > decrease in insulin secretion
-> rise in glucagon secretion Low blood-glucose level
-> stimulates glucagon secretion of α-cells of the pancreas
Glucagon:
-> signals starved state
-> mobilizes glycogen stores (break down)
-> inhibits glycogen synthesis
-> main target organ is liver
-> inhibits fatty acid synthesis
-> stimulates gluconeogenesis in liver
-> large amount of glucose in liver released to blood stream
-> maintain blood-glucose level
Muscle + Liver use fatty acids as fuel when blood-glucose
level drops
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EARLY FASTING STATE -> DURING THE NIGHT
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LIVER FUNCTION IN THE FASTING STATE
PROLONGED STARVATION
FIRST PRIORITY
-> provide sufficient glucose to brain and other tissues that are
dependent on it
SECOND PRIORITY
-> preserve protein
-> shift from utilization of glucose to utilization of fatty acids + ketone
bodies
-> mobilization of TAG in adipose tissues + gluconeogenesis by liver
-> muscle shift from glucose to fatty acids as fuel
AFTER 3 DAYS OF STARVATION
-> liver forms large amounts of ketone bodies
-> brain and heart start to use ketone bodies as fuel
AFTER SEVERAL WEEKS OF STARVATION
-> ketone bodies major fuel of brain
AFTER DEPLETION OF TAG STORES
-> proteins degradation accelerates
-> death due to loss of heart, liver, and kidney function
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PROLONGED STARVATION
20
+
-
PFK
-
-
Fruc.
Bisphos.
Summary:
Glucose
Homeostasis
During
Fasting
THANKS
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