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Integrated Metabolism
• Biochemistry of the organs– Liver Muscle Kidney– Heart Brain Adipose
• Communication between organs– Cori cycle Glucose-Alanine cycle
• Metabolic stress– Starvation and ketosis– Diabetes and ketosis
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Liver (The major anabolic organ)Biosynthesis of blood constituents
Plasma proteinsGluconeogenesisGlycogenFatty acids, triacylglycerolsCholesterolKetone bodiesVLDL, HDLUrea synthesisBile salts
Plasma proteinsGluconeogenesisGlycogenFatty acids, triacylglycerolsCholesterolKetone bodiesVLDL, HDLUrea synthesisBile salts
Communication with other organsTarget of hormones
Rich in mitochondria
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Fed Liver
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Fasting Liver
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Brain
Major glucose consumerLimited energy storesOxygen dependentMajor ATP producerConsumes glucose and ketone bodiesHormone insensitiveShielded by BBB
Major glucose consumerLimited energy storesOxygen dependentMajor ATP producerConsumes glucose and ketone bodiesHormone insensitiveShielded by BBB
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Heart
Completely aerobic Consumes mostly fat, low glucose useMitochondria richLow energy reservesConsumes ketone bodiesInsulin insensitive
Completely aerobic Consumes mostly fat, low glucose useMitochondria richLow energy reservesConsumes ketone bodiesInsulin insensitive
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Muscle
Uses all fuel sourcesExertion uses glucose; no exertion fatty acidsRelies on glycogen during exertionRequires insulin to absorb blood glucoseMajor producer of blood lactate-anaerobicStores ATP energy as creatine-PO4 (phosphocreatine)
Uses all fuel sourcesExertion uses glucose; no exertion fatty acidsRelies on glycogen during exertionRequires insulin to absorb blood glucoseMajor producer of blood lactate-anaerobicStores ATP energy as creatine-PO4 (phosphocreatine)
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Adipose Cells
Major depositors of energyHormone-sensitive lipaseInsulin-dependent glucose transportTriacylglycerol synthesis glucose-dependentLacks glycerol kinase
Major depositors of energyHormone-sensitive lipaseInsulin-dependent glucose transportTriacylglycerol synthesis glucose-dependentLacks glycerol kinase
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KidneyKidney
70% of ATP used for resorption
Weak gluconeogenic activityGlucose-6-phosphatase
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Pancreas
Secretes digestive enzymes in inactive formAlpha cells make glucagonBeta cells make insulinDelta cells make somatostatinResponsive to blood glucose
Secretes digestive enzymes in inactive formAlpha cells make glucagonBeta cells make insulinDelta cells make somatostatinResponsive to blood glucose
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PANCREAS
3 types of cells
Alpha: glucagonBeta: Insulin
Delta: somatostatin
Regulation of Insulin Secretion
p. 903p. 903
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CHO
HO-C-H
CH2OPO3=
COO
HO-C-H
CH2OPO3=
COO
CH3
C=O
COO
CH3
HO-C-H
NAD+ NADH + H+
PyruvateL-lactate
Glyceraldehyde- 3-phosphate
3-phospho- glycerate
Communication in Pathways
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CHOCCCCCH2OH
COO-C| |CH2
~OPO3
COO-C=OCH3
CHOCCCCCH2OPO3
GlucoseATP ADP ADP
ATP
Pyruvate
PEP
Glucose 6-P
pyruvate kinase
hexose kinase
ATP
ATP-ADP CYCLE
Communication within Pathways
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THE CORI CYCLETHE CORI CYCLE
Liver
L-lactate D-glucose
D-glucoseL-lactate
BloodGlucose
BloodLactate
Muscle
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THE Glucose-Alanine Cycle
THE Glucose-Alanine Cycle
LiverD-glucose
D-glucose
BloodGlucose
BloodAlanine
Muscle
Pyruvate
L-Alanine
NH4 Glycolysis
L-Alanine
Pyruvate
GluconeogenesisNH4Urea