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Today’s topics: Amino Acid Metabolism Review Oxidative deamination of GLU

Today’s topics: Amino Acid Metabolism Review Oxidative deamination of GLU Transamination + Oxidative deamination to remove other aa s Ubiquitin & protein breakdown Metabolic review Phenylalanine breakdown and PKU . Metabolic Mainstreet. Glucose. Glycolysis. Pyruvate.

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Today’s topics: Amino Acid Metabolism Review Oxidative deamination of GLU

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  1. Today’s topics: Amino Acid Metabolism Review Oxidative deamination of GLU Transamination + Oxidative deamination to remove other aas Ubiquitin & protein breakdown Metabolic review Phenylalanine breakdown and PKU

  2. Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  3. Aerobic ~ 36 ATP Anaerobic 2 ATP LDH Lactate Glycerol phosphate shuttle Metabolic Mainstreet Glucose NAD+ Glycolysis NADH Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  4. Fed state - insulin Glycogenesis→ Glycogen Glucose-6-P • Glycogenolysis • fasting state – glucagon • muscle - epinephrine Glucose Glycolysis Pyruvate Glycogen Metabolism liver & muscle Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  5. Gluconeogenesis(liver) Protein Ubiquitin /Proteosome Amino Acids Glucose glucogenic Pyruvate ketogenic Transamination Oxidative deamination AcetylCoA NAD+/FAD glucogenic NADH/FADH2 C6 oxaloacetate C4 Citric Acid Cycle ADP O2 C5 C4 ATP

  6. NADPH CO2 Ribose-5-P PPP TK/TA acetoacetylCoA ketone bodies (liver) Fat (triglycerides) (adipose) Glucose Lipase (fasting) fed Fatty acid synthesis Fatty acids Pyruvate b-oxidation AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  7. Metabolism & Cell Type • Brain: Glucose only (normal) adapts to 75% KB utilization (long term fast) PPP to make NADPH to protect neurons from ROS • Liver: Fasting: ↓Glycolysis Exports Glucose via glycogenolysis & …. gluconeogenesis + ketone body formation Fed: makes glycogen & Fatty acids/cholesterol • Muscle: Maintains glycogen to allow anaerobic metabolism Glycogenolysis and Glycolysis in exercise (anaerobic) Glycogenesis during Fed + Resting state • Adipose: Fasting: ↑Lipase (glucagon) – exports fatty acids Fed: PPP to make NADPH for FA synthesis • Heart Muscle: KB’s as fuel – avoid anaerobic activity

  8. Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  9. Brain Cells fed + early/late fast Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  10. acetoacetylCoA ketone bodies (from liver) 25% from Liver Gluconeogenesis Brain Cells Long term fast Glucose Pyruvate 75% AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  11. NADPH CO2 Ribose-5-P PPP TK/TA Fat (triglycerides) Glucose Fatty acid synthesis Fatty acids Pyruvate Adipose: Fed state AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  12. Fat (triglycerides) Glucose Lipase (fasting) Fatty acids Pyruvate to blood b-oxidation AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 Adipose: fasting state C4 ATP

  13. Glycogenesis Glucose-6-P Glycogen Muscle fed state at rest Glucose Glycolysis Pyruvate Fatty acids Bridging Rx. b-oxidation AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  14. Glucose-6-P Glycogen Glycogenolysis Muscle Anaerobic exercise Glucose X Glycolysis Muscle McArdle’s Disease X Pyruvate Lactate LDH Bridging Rx. Fatty acids AcetylCoA b-oxidation NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  15. Glycogenesis NADPH CO2 Ribose-5-P PPP TK/TA Glucose-6-P Glycogen Glucose to blood Fatty acid synthesis Fatty acids Pyruvate Liver: Fed state AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  16. Glycogenolysis Glucose-6-P Glycogen to blood Glucose Liver early fast Glycolysis Pyruvate Bridging Rx. Fatty acids AcetylCoA b-oxidation NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP

  17. Protein Amino Acids acetoacetylCoA ketone bodies Gluconeogenesis Liver late fast Glucose blood Pyruvate Fatty acids AcetylCoA NADH/FADH2 NAD+/FAD C6 oxaloacetate C4 Citric Acid Cycle also in diabetes fed state ADP O2 C5 C4 ATP

  18. Liver long term fast Protein Amino Acids acetoacetylCoA ketone bodies Gluconeogenesis Glucose blood Pyruvate Fatty acids AcetylCoA NADH/FADH2 NAD+/FAD C6 oxaloacetate C4 Citric Acid Cycle ADP O2 C5 C4 ATP

  19. Insulin release Glucagon release [Glu] blood Meal Glycogen broken down to provide glucose Blood Glucose concentrations normal fasting levels = 60 – 100 mg/dL Fed state ~2 hrs ~12 hrs

  20. early long term ~ 3 days late Lipolysis Brain uses Ketone bodies Protein conserved Fasting State Absent with Atkins Meal – lipolysis continues Glycogen broken down to provide glucose Fatty acids from adipose Protein broken down to make glucose Fatty acids from adipose

  21. high glycemic index – low fat diet diabetic Atkins [Glu] blood insulin resistance (metabolic syndrome) Meal Fed 60 – 100 mg/dL ~2 hrs ~12 hrs

  22. 1992 USDA Food Pyramid - Low fat diet fads What constitutes low fat? < 30% of calories from fat extreme diet < 10% Fats use sparingly Dairy Meat, Fish 2-3 Eggs, Beans 2-3 Vegetables 3-5 Fruits 2-4 Bread, cereal, rice, pasta 6-11

  23. Red meat, butter, white rice, bread, potatoes, pasta, sweets Willett, Walter (2005). Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating. Free Press. ISBN 0-7432-6642-0 Healthy Eating Pyramid use sparingly Dairy/Ca supp 1-2 Multiple vitamin Fish, poultry, eggs 0-2 Nuts & legumes 1-3 Vegetables (lots) Fruits 2-3 Whole grain Plant oils Exercise & weight control

  24. 2001 USDA Food Pyramid (www.MyPyramid.gov) Fats sugars Na use sparingly 7 teaspoon = daily limit on oils Fruits 2 cups weekly Vegetables 3 cups weekly Milk 3 cups (Ca rich foods– low fat) Meat & beans: lean meats more fish, beans, nuts, peas, seeds Grains 8 oz.4 oz. whole grain

  25. ‘FAD’ Diets Atkins Diet ― very low carbohydrate (no portion limits) South Beach Diet ― milder form of Atkins Zone Diet ― 40:30:30 (% of calories from carbohydrate – protein – fat) Mediterranean Diet ― 40% calories from fat but monounsaturated Low Fat Diet ― < 10% calories from fat ‘Eating Plans’ USDA – 1992 Food Pyramid 2001 Food Pyramid Willet – Healthy eating Pyramid Common Features: 1) exercise 2) Eat your Veggies Majority Features: 1) minimize saturated fats 2) minimize high Glycemic index Carbs 3) replace 1-2 with whole grains/fruits/unsaturated fats 4) portion control

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