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

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

Fed Liver

Fasting Liver

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

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

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)

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

KidneyKidney

70% of ATP used for resorption

Weak gluconeogenic activityGlucose-6-phosphatase

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

PANCREAS

3 types of cells

Alpha: glucagonBeta: Insulin

Delta: somatostatin

Regulation of Insulin Secretion

p. 903p. 903

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

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

THE CORI CYCLETHE CORI CYCLE

Liver

L-lactate D-glucose

D-glucoseL-lactate

BloodGlucose

BloodLactate

Muscle

THE Glucose-Alanine Cycle

THE Glucose-Alanine Cycle

LiverD-glucose

D-glucose

BloodGlucose

BloodAlanine

Muscle

Pyruvate

L-Alanine

NH4 Glycolysis

L-Alanine

Pyruvate

GluconeogenesisNH4Urea