Fed State Insulin Glucagon Epinephrine Fasted State Starvation

Fed State Insulin

Glucagon/ Epinephrine Fasted State/ Starvation

Hexokinase/ * Glucokinase * * Pyruvate kinase Phosphofructokinase-1

HEXOKINASE inhibited by Glu 6 -P * * GLUCOKINASE USED IN LIVER Fructose 6 -P reduces activity by causing enzyme to translocate to nucleus *

* Phosphofructokinase-1 * + Fructose 2, 6 - bis. P AMP - ATP, citrate - Glucagon & Epinephrine in Liver *

* * Pyruvate Kinase + fructose-1, 6 -bis. P - ATP, alanine - glucagon & epinephrine *

Glucokinase Liver: Insulin Increases Transcription Of Genes Encoding These Enzymes PFK-1 Pyruvate Kinase *

* Liver: * PFK-2/ PFK-1 Glucagon Epinephrine Pyruvate Kinase *

* PFK-2/ PFK-1 Heart: * Epinephrine *

Pyruvate Dehydrogenase (PDH) Lactate Alanine PDH Gene Deficiency: Lactic Acidosis Neurological Defects Treatment – ketogenic diet PDH Activity Low Thiamine Deficiency Arsenic Poisoning

Galactosemia Treatment: Eliminate galactose/ Lactose MILK

Treatment: Decrease fructose/sucrose

Glucose Homeostasis is Required for Survival Glucose Glycogen Pi Glucose 6 -Phosphatase Glucose 6 -Phosphate Gluconeogenesis Pyruvate Glycogen Degradation Glycogen Phosphorylase Kinase Glucose 1 -Phosphate

Glucose 6 -phosphatase Glucose 6 -phosphaate Triacylglycerol Fructose 6 -phosphate Fructose 1, 6 -bisphosphatase -F-2, 6 -bis. P -AMP Fructose 1, 6 -bisphosphate Glyceraldehyde 3 -phosphate 1, 3 Bisphoglycerate 3, Phosphoglycerate Glycolysis In other Tissues Glycerol Dihydroxyacetone phosphate Muscle Protein Phosphoenolpyruvate Carboxykinase *** Oxaloacetate Some amino acids Pyruvate carboxylase Lactate Pyruvate Some amino acids +Ac. Co. A requires biotin

Ethanol metabolism can cause hypoglycemia; the high NADH opposes gluconeogenesis Ethanol metabolism increases NADH Increased NADH promotes the conversion of two glucogenic precursors (pyruvate and oxaloacetate) to lactate and malate. This removes pyruvate and oxaloacetate from the pool of glucogenic precursors.

Pentose Phosphate Pathway (Hexose Monophosphate Shunt) Generates: NADPH – Lipid Biosynthesis Ribose 5 -Phosphate – Purine Biosynthesis – e. g. , DNA, RNA, Co. A

A Genetic Deficiency of Glucose 6 -Phosphate Dehydrogenase is Associated with Drug-Induced Hemolytic Anemia.

Malaria Glucose 6 - Phosphate Dehydrogenase Deficiency Shaded Countries: > 1/200 men with deficiency 5 -25% in Tropical Africa, Middle East, Tropical Asia, Mediterranean

Fed State Insulin Dietary Glucose Insulin

Dietary Fat

Epinephrine

Acetyl Co. A Carboxylase Citrate, Insulin + - Long Chain Fatty Acids Glucagon, Epinephrine Biotin

Chylomicron-TAG (from intestines) Insulin PGs - + Epinephrine

Epinephrine X X

Carnitine transports fatty acids into the mitochondrial matrix. CPT – 1 Only Inhibitor Is Malonyl-Co. A

Ketone bodies: Beta-hydroxybutyrate Acetoacetate acetone

LDL Metabolism “Statins” Inhibit HMC-Co. A Reductase

Two Pathways of LDL Clearance HDL 2 Oxidized LDL

HDL is involved with reverse cholesterol transport

* treatment

* * * Infantile only * * * Mental Retardation

From Lippincott

From Lippincott

Type 1 Collagen Triple-stranded Gly-X-Y repeat Glycine – smallest aa Proline – polyproline helix OH-pro, OH-lys H-bonding Lysine aldehydes cross-linking

Disorder Selected Collagen Disorders Collagen synthesis Clinical Manifestations Osteogenesis Imperfecta 1 Decreased synthesis of type 1 collagen Autosomal Dominant – may act like dominant negative Osteogenesis Imperfecta 2 Point mutations & rearrangement of exons in triple helical regions Autosomal Dominant Ehlers. Danlos susceptibility to fractures sometimes confused with child abuse blue sclerae - translucent connective tissue over choroid Perinatal death; soft, fragile & malformed bones Faulty collagen synthesis Hyperextensive skin, hypermobility of joints, tendency to bleed

Fibrillin is essential to the integrity of elastin Marfan’s Syndrome mutation in the fibrillin gene

Glycogen Synthase Phosphorylase Kinase Glycogen Phosphorylase UDP-Glucose • Pentose Phosphate Pathway (NADPH ribose 5 -P, glycolytic intermediates) Glucose 1 -P Glucose Hexokinase/Glucokinase Glucose-6 -P Glucose 6 -Phosphatase Fructose-1, 6 -Bisphosphatase Phosphofructokinase-1 (PFK 1) Triose Phosphates (Glyceraldehyde 3 -P Dehydrogenase) Pyruvate Kinase PEP Carboxykinase Lactate Dehydrogenase 2 Pyruvate Carboxylase 2 Lactate Pyruvate Dehydrogenase Acetyl-Co. A Oxaloacetate Precursor of Lipids Citrate Formed from Fatty Acid and Ketone Metabolism CO 2, H 2 O, 12 ~ P