Integrated Metabolism Biochemistry of the organs –LiverMuscleKidney –HeartBrainAdipose Communication between organs –Cori cycleGlucose-Alanine cycle Metabolic stress –Starvation and ketosis –Diabetes and ketosis

Liver (The major anabolic organ) Biosynthesis of blood constituents Plasma proteins Gluconeogenesis Glycogen Fatty acids, triacylglycerols Cholesterol Ketone bodies VLDL, HDL Urea synthesis Bile salts Plasma proteins Gluconeogenesis Glycogen Fatty acids, triacylglycerols Cholesterol Ketone bodies VLDL, HDL Urea synthesis Bile salts Communication with other organs Target of hormones Rich in mitochondria

Fed Liver

Fasting Liver

Brain Major glucose consumer Limited energy stores Oxygen dependent Major ATP producer Consumes glucose and ketone bodies Hormone insensitive Shielded by BBB Major glucose consumer Limited energy stores Oxygen dependent Major ATP producer Consumes glucose and ketone bodies Hormone insensitive Shielded by BBB

Heart Completely aerobic Consumes mostly fat, low glucose use Mitochondria rich Low energy reserves Consumes ketone bodies Insulin insensitive Completely aerobic Consumes mostly fat, low glucose use Mitochondria rich Low energy reserves Consumes ketone bodies Insulin insensitive

Muscle Uses all fuel sources Exertion uses glucose; no exertion fatty acids Relies on glycogen during exertion Requires insulin to absorb blood glucose Major producer of blood lactate-anaerobic Stores ATP energy as creatine-PO 4 (phosphocreatine) Uses all fuel sources Exertion uses glucose; no exertion fatty acids Relies on glycogen during exertion Requires insulin to absorb blood glucose Major producer of blood lactate-anaerobic Stores ATP energy as creatine-PO 4 (phosphocreatine)

Adipose Cells Major depositors of energy Hormone-sensitive lipase Insulin-dependent glucose transport Triacylglycerol synthesis glucose-dependent Lacks glycerol kinase Major depositors of energy Hormone-sensitive lipase Insulin-dependent glucose transport Triacylglycerol synthesis glucose-dependent Lacks glycerol kinase

Kidney 70% of ATP used for resorption Weak gluconeogenic activity Glucose-6-phosphatase

Pancreas Secretes digestive enzymes in inactive form Alpha cells make glucagon Beta cells make insulin Delta cells make somatostatin Responsive to blood glucose Secretes digestive enzymes in inactive form Alpha cells make glucagon Beta cells make insulin Delta cells make somatostatin Responsive to blood glucose

PANCREAS 3 types of cells Alpha: glucagon Beta: Insulin Delta: somatostatin Regulation of Insulin Secretion p. 903

CHO HO-C-H CH 2 OPO 3 = COO HO-C-H CH 2 OPO 3 = COO CH 3 C=O COO CH 3 HO-C-H NAD + NADH + H + Pyruvate L-lactate Glyceraldehyde- 3-phosphate 3-phospho- glycerate Communication in Pathways

CHO C C C C CH 2 OH COO - C | | CH 2 ~ OPO 3 COO - C=O CH 3 CHO C C C C CH 2 OPO 3 Glucose ATP ADP ADP ATP Pyruvate PEP Glucose 6-P pyruvate kinase hexose kinase ATP ATP-ADP CYCLE Communication within Pathways

THE CORI CYCLE Liver L-lactateD-glucose L-lactate Blood Glucose Blood Lactate Muscle

THE Glucose-Alanine Cycle THE Glucose-Alanine Cycle Liver D-glucose Blood Glucose Blood Alanine Muscle Pyruvate L-Alanine NH 4 Glycolysis L-Alanine Pyruvate Gluconeogenesis NH 4 Urea