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Metabolic Mainstreet. Glucose. Glycolysis. Pyruvate. Bridging Rx. AcetylCoA. NADH/FADH 2. C 6. C 4. OP. Citric Acid Cycle. ADP O 2. C 5. C 4. ATP. Aerobic ~ 36 ATP. Anaerobic 2 ATP. LDH. Lactate. Glycerol phosphate shuttle. Metabolic Mainstreet. Glucose. NAD +.
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Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP
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
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
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
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
Metabolism & Cell Type Brain: Glucose only (normal) adapts to 75% KB utilization (long term fast) Liver: Exports Glucose via glycogenolysis and gluconeogenesis makes Fatty acids/cholesterol (fed) – ketone bodies (fast) Muscle: Maintains glycogen to allow anaerobic metabolism Adipose: Fat storage – Lipase (glucagon) - leptin secretion Heart Muscle: KB’s as fuel – avoid anaerobic activity
Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NADH/FADH2 C6 C4 OP Citric Acid Cycle ADP O2 C5 C4 ATP
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
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
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
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
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
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
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
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
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
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
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
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
high glycemic index – low fat diet diabetic Atkins [Glu] blood insulin resistance (metabolic syndrome) Meal Fed 60 – 100 mg/dL ~2 hrs ~12 hrs
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
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
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
‘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
Our hunter-gatherer ancestors relied on a wide variety of fruits and vegetables, scrabbling to pick and eat whatever they could find that was tasty. Desire for carbohydrates (sweetness) was balanced by its scarcity, and existed only in forms that included high fiber. Random dietary advice ….. Hydration – page 129 – tap water (over-hyped water in food counts) Diet drinks – page 130 (safe - better than sugar drinks – water is best) Coffee – 132-133 (safe in moderation, beware caffeine) tea – 134 (less caffeine than coffee, more antioxidants ) alcohol – 135-137 (moderation! – 1-2 drinks ok for men –breast cancer correlation in women) Ca – 151 (over-hyped – 500-1000 mg supplements (> dairy) for post-menopausal women) Antioxidants – 154 – 157 (over-hyped – drink tea, eat fruits/veggies) Vitamin C – 161 (over-hyped – RDI = 75 mg/day; 200-300 probably good) Fe – 169-170 (not a major problem in US) Na - 173-174 (minority predisposed to hbp - we get too much in diet - ↓processed foods) fiber – 97 – 98 (cancer benefit probably false but - ↓cholesterol and ↓Glycemic index) Protein – 0.4g • body weight (in lbs) – 104 (nuts/veggie sources > lean meats > red meat)