Metabolic interrelationship in well fed state   ط      Metabolic integration during well fed state ط     Inter-organ  relationship ط     Hormonal balance: Insulin/glucagon ratio                                           N L3  537-45  ;  D4   528-29

Metabolic Interrelation Well-Fed State fig13.2 D4 (Mixed Fuels) Early-Fasting State fig13.3 D4 (3-4 hr post-absorptive period) Fasting State fig13.4 D4 (early / Intermediate / prolonged starvation) Re-fed State fig13.6 D4

Metabolic Interrelation 1. Well-Fed State fig13.2 D4 (Mixed Fuels) - In well-fed state the diet supplies the energy requirement (Glc, AA, fat) - increase INS : Glg ratio (Glc, AA, fat)

Metabolic Interrelation 1. Well-Fed State fig13.2 D4 (Mixed Fuels) * Carbohydrate (diet) => Glc (liver) activated by INS => a) produce NADPH b) stored as Glycogen c) Oxidized to Pyruvate => · anaerobically produce Lactate · complete oxidation (aerobically) through TCA cycle => CO2 + H2O · converted to fat (G3P => glycerol) and stored in AT or muscle - no cori cycle Glc (liver) => other tissues activated by INS d) Brain/Testis (main source): CO2 + H2O e) RBCs/Adrenal Medulla (only source): Pyruvate/Lactate f)  Adipose tissue: fat g) Muscle: Glycogen / CO2 + H2O

Metabolic Interrelation 1. Well-Fed State fig13.2 D4 (Mixed Fuels) * Protein (diet) => AA (liver) activated by INS => a) usually AA pass liver (↑Km Enzs, except tRNA Enz during growth) to all tissues and activated by INS => ·  synthesize protein ·  enters the carbon skeleton & oxidized completely => CO2 + H2O b) if concentration of dietary AA is high it does not pass the liver ·  produce urea ·  converted to fat =>transported by VLDL, stored in AT & muscle

Metabolic Interrelation 1. Well-Fed State fig13.2 D4 (Mixed Fuels) * Fat (diet) => Chylomicron (lymph) => a) reaches Adipose tissue ·         Stored as TG b)  reaches muscle ·         Stored TG ·         Oxidized to CO2 + H2O

Metabolic Interrelation 2. Early-Fasting State fig13.3 D4 (3-4 hr post-absorptive period) - In early fasting, hepatic glycogenolysis is an important source of bld glc Fat & prt reduce gastric emptying fig13.3 D4, fig14.1 NL3 * Glycogen (liver) activated by Glg => Glc (gluconeogenesis) => other tissues a) Muslce: alanine cycle b) RBCs: cori cycle c) Brain: CO2 + H2O - End stage: bld glc and ins are low - no protein synthesis

Metabolic response to starvation ط     Stages of starvation and hormonal balance ط     Post absorptive period : Duration and characters ط     Early starvation : Duration and  fuel  utilization ط     Intermediate starvation : Duration and fuel utilization, glucose alanine and fatty acid cycle ط     Prolonged starvation : characters and causes of death after prolonged starvation ط     Refeeding after prolonged starvation ط     Integration of carbohydrates, Lipid and protein metabolism during starvation ط     Regulatory role of ketone Bodies and T3 in starvation                                           N L3 545-9;  D4   529 -34 

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) In fasting state, gluconeogenesis is required from AAs & glycerol A. Fasting State (early starvation) · Early stage: most tissues utilize glc fig13.4 D4, fig14.2, Table14.1 NL3 · Then: only brain & anaerobic tissues · This will increase FA oxid in muscle & other tissues (e.g. kidneys) · Up to 24 hours

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) A. Fasting State (early starvation) * Glucose (liver) => Cori cycle a) Lactate (RBCs) => b) Glucose (liver) => c) Lactate (RBCs) => d)Glucose (liver) =>

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) A. Fasting State (early starvation) * Protein => AA activated by Glucagon a) Protein (Liver) => AA => Glucose ·  Reach brain => Oxidized to CO2 + H2O b) Protein (Muscle) => AA => Alanine / Glutamine ·  Alanine reaches liver => gluconeogenesis to glucose + urea - Glucose reach brain => Oxidized to CO2 + H2O - Urea reaches kidney => excreted · Glutamine reaches Gut => Alanine - alanine reaches liver => gluconeogenesis to glucose + urea * glucose to brain => oxidized to CO2 + H2O * urea to kidneys => excretion

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) A. Fasting State (early starvation) * Fat (Adipose tissue) => Hydrolyzed to Glycerol + Fatty Acids a)       Glycerol + Fatty Acids reach Liver ·         Glycerol => Glucose - reaches brain => Oxidized to CO2 + H2O ·         Fatty Acids => Ketone bodies - reaches muscle => Oxidized to CO2 + H2O b)       Fatty Acids reaches muscle ·         Oxidized to CO2 + H2O

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) B. Intermediate Starvation · Early stage: high gluconeogenesis (lact, glycerol, G-AA) fig14.3, Table14.3 NL3 · Later stage: high KB · 1-24 days

Metabolic Interrelation 3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation) C. Prolonged Starvation · Low prt degrade – enz activity (AAs) fig14.4, Table14.4 NL3 · The rate of carb, lipid, prt metab reach steady state · Constant high KB concentration · Low N excretion · Ends with Re-feeding or death · Death is caused by pneumonia, low Ab, shock

Metabolic Interrelation Role of KB · 2-24 days: high KB is produced for brain, nervous tissue, kidney cortex, s.intest epithelial cells, heart · Also decrease in glc utilization, FA oxid and prt degrad in other tissues

Metabolic Interrelation Role of T3 · Thyroxine does not control metab rate · Starve 2-3 days decrease basal metab rate (not thyroxine) · The active for is triiodothyronine (T3) · During starvation: decrease production of T3 from T4 Increase production of reverse-T3 from T4 · This is to control prt deg & energy expenditure · Hypothyroid during starvation decrease prt breakdown and urea excretion and increase survival

Metabolic Interrelation 4. Re-fed State fig13.6 D4 (after fasting / after starvation) In early-refed state, fat is metabolized normally and normal glucose metabolism is slowly re-established A. Early Re-feeding After Fasting · Glc is the main fuel in breakfast fig13.6 D4, fig14.10 NL3

Metabolic Interrelation A. Early Re-feeding After Fasting * Carbohydrate (diet) => Glc (liver) activated by INS => a) Glc reach brain => oxidized to CO2 + H2O b) Glc reaches Adipose tissue => converted to fat (G3P => glycerol) and stored c) Glc reaches muscle => stored as Glycogen d) Glc reaches RBCs => Lactate ·  Lactate reaches liver => glc stored as glycogen

Metabolic Interrelation A. Early Re-feeding After Fasting * Protein (diet) => AA (liver) activated by INS => a) AA (liver) => ·  Stored as Glycogen + release Urea ·  Protein Synthesis b) AA reach all tissues => ·  synthesize protein

Metabolic Interrelation A. Early Re-feeding After Fasting * Fat (diet) => Chylomicron (lymph) => a) reaches Adipose tissue ·  Stored as TG b) reaches muscle ·  Stored TG ·  Oxidized to CO2 + H2O

Metabolic Interrelation B. Re-feeding After Starvation · Same as re-feeding after fasting plus high prt-AA metab · 2 days: increase Glg, GH GC and deacrease INS lead to hogh FA, KB, Glc, AA · 2-4 days; FA, Glc , KB ratio fig14.5 NL3