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Fed State

Fed State. Insulin. Insulin. Glucagon/ Epinephrine. Fasted State/ Starvation. Glucagon/ Epinephrine. Glucagon/ Epinephrine. Hexokinase/ Glucokinase. *. Phosphofructo- kinase-1. *. Pyruvate kinase. *. *. HEXOKINASE inhibited by Glu 6-P GLUCOKINASE USED IN LIVER

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Fed State

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  1. Fed State Insulin Insulin

  2. Glucagon/ Epinephrine Fasted State/ Starvation Glucagon/ Epinephrine Glucagon/ Epinephrine

  3. Hexokinase/ Glucokinase * Phosphofructo- kinase-1 * Pyruvate kinase *

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

  5. * Phosphofructo- kinase-1 + Fructose 2,6- bisP AMP - ATP, citrate - Glucagon & Epinephrine in Liver * *

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

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

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

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

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

  11. Galactosemia Treatment: Eliminate galactose/ Lactose MILK

  12. Treatment: Decrease fructose/sucrose

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

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

  15. 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.

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

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

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

  19. Fed State Insulin Dietary Glucose Insulin

  20. Dietary Fat

  21. Epinephrine Epinephrine

  22. Acetyl CoA Carboxylase Citrate, Insulin + Biotin - Long Chain Fatty Acids Glucagon, Epinephrine

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

  24. Epinephrine X X

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

  26. Ketone bodies: Beta-hydroxybutyrate Acetoacetate acetone

  27. LDL Metabolism “Statins” Inhibit HMC-CoA Reductase

  28. Two Pathways of LDL Clearance Oxidized LDL HDL2

  29. HDL is involved with reverse cholesterol transport

  30. * treatment * treatment * treatment

  31. * * Infantile only * * * * Mental Retardation

  32. From Lippincott

  33. From Lippincott

  34. 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

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

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

  37. Glycogen Glycogen Synthase Phosphorylase Kinase Glycogen Phosphorylase UDP-Glucose • Pentose Phosphate Pathway Glucose 1-P (NADPH ribose 5-P, glycolytic intermediates) Hexokinase/Glucokinase Glucose Glucose-6-P Glucose 6-Phosphatase Phosphofructokinase-1 (PFK1) Fructose-1,6-Bisphosphatase Triose Phosphates (Glyceraldehyde 3-P Dehydrogenase) Pyruvate Kinase PEP Carboxykinase Lactate Dehydrogenase 2 Lactate 2 Pyruvate Pyruvate Carboxylase Pyruvate Dehydrogenase Acetyl-CoA Precursor of Lipids Citrate Oxaloacetate Formed from Fatty Acid and Ketone Metabolism CO2, H2O, 12 ~ P

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