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REGULATION OF BODY WEIGHT

REGULATION OF BODY WEIGHT. THE BIOCHEMISTRY OF APPETITE AND ENERGY EXPENDITURE. REGULATION OF BODY WEIGHT. OVERVIEW ORGAN SPECIALIZATION METABOLIC PATHWAYS HOMEOSTASIS PROTEINS INVOLVED IN WEIGHT REGULATION DYSREGULATION STARVATION OBESITY DIABETES: TYPES I AND II DIETING ATKINS DIET.

thaddeus-lowery
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REGULATION OF BODY WEIGHT

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  1. REGULATION OF BODY WEIGHT THE BIOCHEMISTRY OF APPETITE AND ENERGY EXPENDITURE

  2. REGULATION OF BODY WEIGHT • OVERVIEW • ORGAN SPECIALIZATION • METABOLIC PATHWAYS • HOMEOSTASIS • PROTEINS INVOLVED IN WEIGHT REGULATION • DYSREGULATION • STARVATION • OBESITY • DIABETES: TYPES I AND II • DIETING • ATKINS DIET

  3. OVERVIEW 1 • NORMAL METABOLISM IS A HIGHLY CONTROLLED AND REGULATED BALANCE BETWEEN ANABOLISM AND CATABOLISM • CATABOLIC PROCESSES RELEASE CHEMICAL ENERGY STORED IN COMPLEX MOLECULES • ENERGY SAVED AS ATP, NADH, NADPH, FADH2 • OR USED AS NEEDED IN VARIOUS PROCESSES • ANABOLIC PROCESSES BUILD COMPLEX MOLECULES FROM SIMPLER MOLECULES • REQUIRE ENERGY, USUALLY FROM ATP, NADH, NADPH • METABOLIC FUELS (STORAGE MOLECULES) • PROTEINS • POLYSACCHARIDES • LIPIDS • NUCLEOTIDE METABOLISM :ONLY A VERY SMALL ROLE IN ENERGY BALANCE (AT THE LEVEL OF PYRIMIDINE CATABOLISM)

  4. OVERVIEW 2 • PATHWAYS INVOLVED IN ENERGY METABOLISM ARE INTERRELATED • REVIEW THE MAJOR PATHWAYS INVOLVED IN FUEL METABOLISM AND THEIR REGULATION • GLYCOLYTIC/GLUCONEOGENIC • GLYCOGEN METABOLISM • FATTY ACID METABOLISM • CITRIC ACID CYCLE • AMINO ACID METABOLISM • PENTOSE PHOSPHATE PATHWAY • OXIDATIVE PHOSPHORYLATION

  5. OVERVIEW 3 : COMPARTMENTALIZATION • TWO COMPARTMENTS IN WHICH METABOLISM IS DIVIDED: • CYTOSOL • GLYCOLYSIS • GLUCONEOGENESIS • GLYCOGEN BREAKDOWN AND SYNTHESIS • PENTOSE PHOSPHATE PATHWAY • FATTY ACID SYNTHESIS • AMINO ACID DEGRADATION AND UREA CYCLE • MITOCHONDRIA • CITRIC ACID CYCLE • OXIDATIVE PHOSPHORYLATION • FATTY ACID OXIDATION • AMINO ACID DEGRADATION AND UREA CYCLE • MEMBRANE TRANSPORT BETWEEN CYTOSOL AND MITOCHONDRIA

  6. OVERVIEW 4 • MITOCHONDRIAL-CYTOSOLIC INTERFACE • MITOCHONDRIAL MEMBRANE TRANSPORTERS: • PYRUVATE TRANSPORTER • CARNITINE/ACYLCARNITINE TRANSPORTER • CITRATE TRANSPORTER • ASPARTATE TRANSPORTER • MALATE TRANSPORTER • CITRULLINE TRANSPORTER • ORNITHINE TRANSPORTER • OTHERS

  7. OVERVIEW 5 • ORGANS ARE SPECIALIZED WITH REGARD TO METABOLISM • DIFFERENT METABOLIC NEEDS AND FUNCTIONS • INTER-ORGAN COORDINATION WE WILL LOOK AT HOW SPECIFIC METABOLIC FUNCTIONS ARE DISTRIBUTED AMONG THE FOLLOWING ORGANS: • BRAIN • MUSCLE (SKELETAL AND HEART) • LIVER • KIDNEY • ADIPOSE TISSUE

  8. ORGAN SPECIALIZATION: MUSCLE • MUSCLE FUELS: • GLUCOSE • FROM GLYCOGEN • FATTY ACIDS • KETONE BODIES

  9. GLYCOGEN • GLYCOGEN  GLUCOSE-6-PHOSPHATE • G-6-P ENTERS GLYCOLYTIC PATHWAY • MUSCLE LACKS G-6-PHOSPHATASE • SO CANNOT GENERATE GLUCOSE FOR EXPORT • MUSCLE CAN SYNTHESIZE GLYCOGEN FROM GLUCOSE • 1% - 2% OF MASS IN RESTED MUSCLE • GLYCOGEN MOBILIZED FASTER THAN FAT • GLUCOSE METABOLISM BOTH AEROBIC AND ANAEROBIC • FAT METABOLISM ONLY AEROBIC

  10. MUSCLE • CANNOT CARRY OUT GLUCONEOGENESIS • MUSCLE CONTRACTION • DRIVEN BY ATP HYDROLYSIS • AEROBIC OR ANAEROBIC • NEEDS ATP REGENERATION • ATP RESUPPLY • INITIALLY FROM PHOSPHOCREATINE (1st 4s OF MAX. EXERTION) • PHOSPHOCREATINE + ADP  CREATINE + ATP • RESPIRATION (GLYCOLYSIS OF G-6-P) • ANAEROBIC DEGRADATION TO LACTATE • WHEN GLYCOLYTIC FLUX > KREBS, OXPHOS FLUXES

  11. MUSCLE • LACTATE •   pH  MUSCLE FATIGUE • TRANSFERRED TO LIVER VIA BLOOD • HEART MUSCLE • AEROBIC • PRIMARILY FATTY ACIDS AS FUEL • CAN ALSO USE • GLUCOSE (FROM SMALL GLYCOGEN STORE) • KETONE BODIES • PYRUVATE, LACTATE

  12. MUSCLE • CARBOHYDRATE METABOLISM IN MUSCLE SOLELY SERVES MUSCLE • CAN’T EXPORT GLUCOSE • CAN’T PARTICIPATE IN GLUCONEOGENESIS • IN STARVATION • PROTEOLYTIC DEGRADATION OF MUSCLE TO AMINO ACIDS

  13. MUSCLE METABOLISM TO LIVER TO LIVER ALANINE  LACTATE  PYRUVATE  H2O + CO2  INTO BLOOD AMINO ACIDS   PROTEINS GLUCOSE  GLYCOGEN FATTY ACIDS + KETONE BODIES FROM LIVER

  14. INTERORGAN PATHWAYS • IN-CLASS EXERCISE *** DURING MAXIMUM EXERTION, MUSCLES GENERATE LACTATE, WHICH IS RELEASED INTO THE BLOODSTREAM. (1) SHOW THE PATHWAY BY WHICH GLUCOSE IS SYNTHESIZED FROM LACTATE IN THE LIVER. (2) WHY ARE SEPARATE COMPARTMENTS NEEDED FOR THIS. (3) WHY DOESN’T MUSCLE RELEASE PYRUVATE DIRECTLY FOR UPTAKE BY THE LIVER TO REGENERATE GLUCOSE, INSTEAD OF CONVERTING IT TO LACTATE? (4) WHAT IS THE NET COST, IN TERMS OF NUCLEOSIDE TRIPHOSPHATES, OF ONE SYNTHETIC CYCLE?

  15. ADIPOSE TISSUE • STORES AND RELEASES FATTY ACIDS • STORAGE • SUBCUTANEOUS • INTRA-ABDOMINAL • SKELETAL MUSCLE • FATTY ACIDS TRANSPORT: AS LIPOPROTEINS • LIPOPROTEINS: NONCOVALENT PROTEIN-LIPID COMPLEX • CHYLOMICRONS (INTESTINAL MUCOSA) DIETARY TG, CHOL  TISSUES • VLDLS (SYNTHESIZED IN LIVER) : LIVER TISSUE; TG, CHOL • HDLS (PLASMA) : TISSUELIVER CHOL. TRANSPORT • STORED AS TRIGLYCERIDES

  16. TRIACYLGLYCEROLS • FATTY ACID ACYLATION TO ACYL-CoA • ATP-DEPENDENT • ACYL-CoA SYNTHETASES • FATTY ACYL-CoA + GLYCEROL-3-PHOSPHATE  STORED TRIACYLGLYCEROLS • GLUCOSE  DHAP (GLYCOLYSIS) • DHAP + NADH + H+  G-3-P + NAD+ • HYDROLYSIS OF TRIACYLGLYCEROLS FOR FUEL •  FATTY ACIDS + GLYCEROL • WHEN GLUCOSE IS PLENTIFUL, GLYCOLYSIS PREDOMINATES  DHAP  G-3-P • FATTY ACIDS  STORED AS TRIACYLGLYCEROLS

  17. ADIPOSE TISSUE TRIACYLGLYCEROLS FROM LIVER TO LIVER FATTY ACIDS + GLYCEROL WELL-FED TRIACYLGLYCEROLS WELL-FED WELL-FED STATE FROM LIVER GLUCOSE

  18. BRAIN • 20 % OF RESTING O2 CONSUMPTION • FUEL FOR PLASMA MEMBRANE Na+- K+ ATPase • MAINTAINS NEURONAL MEMBRANE POTENTIAL • GLUCOSE IS PRIMARY FUEL • BRAIN DOESN’T STORE MUCH GLYCOGEN •  REQUIRES STEADY SUPPLY OF GLUCOSE • DURING FASTING, STARVATION • KETONE BODIES

  19. BRAIN KETONE BODIES H2O + CO2 FROM LIVER TO BLOOD GLUCOSE

  20. LIVER • A “CENTRAL CLEARINGHOUSE” FOR METABOLITES • ALL NUTRIENTS ABSORBED BY INTESTINES DRAIN DIRECTLY INTO THE LIVER VIA THE PORTAL VEIN • EXCEPT FATTY ACIDS • REGULATES BLOOD GLUCOSE LEVEL • RESPONDS TO: • INSULIN • GLUCAGON • EPINEPHRINE • BLOOD GLUCOSE LEVEL

  21. LIVER • WHAT HAPPENS AFTER CHO INGESTION? • LIVER CELLS ARE PERMEABLE TO GLUCOSE • INSULIN HAS NO DIRECT EFFECT ON UPTAKE • WHEN [GLUCOSE] ~ 6 mM LIVER CONVERTS IT TO G-6-P • GLUCOKINASE IS THE ENZYME • AN ISOZYME OF HEXOKINASE • REVIEW ENZYME KINETICS OF BOTH • KM = 0.1 mM FOR HEXOKINASE; 5 mM FOR GLUCOKINASE • HYPERBOLIC VS SIGMOIDAL KINETICS

  22. LIVER • EARLY SATURATION OF HEXOKINASE • INHIBITION BY G-6-P • GLUCOKINASE ACTIVITY LINEAR AT HIGHER [GLUCOSE] • NOT INHIBITED BY G-6-P • GLUCOKINASE IS MONOMERIC • ALLOSTERISM DOESN’T EXPLAIN KINETICS • OTHER ABSORBED SUGARS  G-6-P IN LIVER

  23. CENTRAL ROLE OF GLUCOSE-6-PHOSPHATE IN CHO METABOLISM • ITS FATE DEPENDS ON DEMAND FOR GLUCOSE • G6P  GLUCOSE (G-6-PHOSPHATASE) • WHEN BLOOD [GLUCOSE] < 5 mM • TRANSPORT TO PERIPHERAL ORGANS • G6P  GLYCOGEN • WHEN GLUCOSE DEMAND IS LOW • WHEN GLUCAGON AND/OR EPINEPHRINE LEVELS  • INDICATES  GLUCOSE DEMAND • GLYCOGEN  G-6-P  GLUCOSE • G-6-P  PYRUVATE (GLYCOLYSIS)  ACETYL CoA • OXIDIZED BY C.A. CYCLE AND OXPHOS OR USED FOR FATTY ACID SYNTHESIS • ALSO PHOSPHOLIPIDS, CHOLESTEROL • PYRUVATE DEHYDROGENASE • G-6-P  HEXOSE-MONOPHOSPHATE SHUNT

  24. INTERORGAN PATHWAYSIN-CLASS STUDY QUESTION *** • AMINO ACIDS CAN BE TRANSAMINATED TO ALANINE IN MUSCLE BY USING PYRUVATE AS THE -KETOACID SUBSTRATE. ALANINE IS RELEASED INTO THE BLOODSTREAM AND CIRCULATES TO THE LIVER. • (1) SHOW HOW ALANINE IS CONVERTED TO GLUCOSE IN THE LIVER. • (2) SHOW THE FATE(S) OF THE AMINO GROUPS TRANSFERRED BY THE AMINO ACIDS METABOLIZED THIS WAY IN MUSCLE • (3) SHOW THE FLUX OF ALANINE’S AMINO GROUP FROM ITS ENTRY INTO THE LIVER TO ITS EXIT AS UREA. START WITH 2 MOLECULES OF ALA.

  25. IN-CLASS STUDY QUESTION • EXPLAIN WHY ALCOHOL CONSUMPTION AFTER STRENUOUS EXERCISE, OR ACCIDENTALLY BY A FASTING CHILD, CAUSES HYPOGLYCEMIA (A LOW BLOOD GLUCOSE LEVEL)

  26. CLINICAL CASE STUDY • A THREE MONTH OLD BABY IS REFERRED TO A DEVELOPMENTAL PEDIATRICIAN BECAUSE SHE HAS POOR HEAD CONTROL, IS HYPOTONIC, AND IS NOT DEVELOPING IN A TYPICAL FASHION. ON EXAMINATION, SHE SHOWS GLOBAL DEVELOPMENTAL DELAY (AT THE LEVEL OF A ONE MONTH OLD) AND IS FEELS LIKE A “RAG DOLL” WHEN PICKED UP. SHE HAS DECREASED MUSCLE MASS AND IS NOT FEEDING WELL. SHE HAD A NORMAL EXAMINATION AT BIRTH, BUT WAS “SMALL FOR GESTATIONAL AGE”. HEAD CIRCUMFERENCE IS NOW IN THE “MICROCEPHALIC” RANGE. • THE PEDIATRICIAN CONSIDERED A METABOLIC CAUSE FOR THE BABY’S SYMPTOMS, AMONG OTHER CAUSES, AND DID AN EXTENSIVE “METABOLIC WORKUP”. ABNORMAL RESULTS INCLUDED: • INCREASED SERUM [PYRUVATE], [LACTATE], [AMMONIA] • INCREASED LEVELS OF SERUM ALANINE AND CITRULLINE • LOW SERUM [ASPARTATE] • LOW FASTING BLOOD GLUCOSE LEVEL • BORDERLINE LOW BLOOD pH *NOTE: THE PHLEBOTOMIST WAS INSTRUCTED TO TRANSPORT THE LACTATE AND PYRUVATE IMMEDIATELY TO THE LAB ON ICE.

  27. CLINICAL CASE STUDY: CONTINUED • THE REMAINDER OF THE BLOOD STUDIES WERE NORMAL. AFTER THE LABS RETURN, A FIBROBLAST CULTURE IS OBTAINED AND A PYRUVATE CARBOXYLASE DEFICIENCY IS DIAGNOSED. • BEFORE THE RESULTS OF THE FIBROBLAST CULTURE ARE AVAILABLE, THE INFANT DEVELOPS A VIRAL SYNDROME WITH FEVER, DEVELOPS SEIZURES AND DIES. • QUESTIONS: • EXPLAIN THE BIOCHEMICAL BASIS FOR EACH OF THE ABNORMAL LAB FINDINGS • “PSYCHOMOTOR RETARDATION” IS THE RESULT OF A LACK OF THE NEUROTRANSMITTERS GLU, ASP AND GABA. WHY DOES PYRUVATE CARBOXYLASE DEFICIENCY RESULT IN DEFICIENCIES OF THESE? • IF THIS INFANT HAD NOT DIED, WHAT WOULD HAVE BEEN SOME POTENTIAL TREATMENTS?

  28. HORMONAL INFLUENCES ON METABOLISM • EPINEPHRINE • CYCLIC AMP AS SECONDARY MESSENGER • GLUCAGON • CYCLIC AMP AS SECONDARY MESSENGER • INSULIN

  29. ACTIONS OF EPINEPHRINE • AS AN INSULIN ANTAGONIST • ACTIVATES MUSCLE GLYCOGEN PHOSPHORYLASE • GLUCOSE-6-P USED IN GLYCOLYSIS • TRIGGERS PHOSPHORYLATION (ACTIVATION) OF HORMONE-SENSITIVE LIPASE IN FAT CELLS • MOBILIZES FAT BY HYDROLYZING TGs • GLYCOGEN BREAKDOWN IN LIVER • ACTIVATES GLUCONEOGENESIS IN LIVER • INHIBITS FATTY ACID SYNTHESIS

  30. THE ACTIONS OF GLUCAGON • ACTIONS RESTRICTED TO THE LIVER • BINDS TO A GLUCAGON RECEPTOR • cAMP AS A SECONDARY MESSENGER • PROTEIN KINASE A IS ACTIVATED • PHOSPHORYLATION • CONTROL AT LEVEL OF PROTEIN PHOSPHORYLN’ • OF GLYCOGEN PHOSPHORYLASE   ACTIVITY • OF GLYCOGEN SYNTHASE   ACTIVITY • OF PYRUVATE KINASE   GLYCOLYTIC ACTIVITY • OF FRUCTOSE -2,6-BIPHOSPHATASE   F-2,6-P   PFK1   GLYCOLYTIC ACTIVITY • AN INSULIN ANTAGONIST

  31. THE ACTIONS OF GLUCAGON •  RATES OF GLYCOGENOLYSIS • G-6-PHOSPHATASE IN LIVER • G-6-PHOSPHATE  GLUCOSE + Pi •  RATES OF GLYCOGEN SYNTHESIS •  RATE OF GLYCOLYSIS IN LIVER • CONSERVE GLUCOSE FOR OTHER ORGANS •  RATES OF GLUCONEOGENESIS • GENERATES GLUCOSE FOR RELEASE TO BLOOD •  RATES OF FATTY ACID SYNTHESIS • FAT BECOMES ENERGY SOURCE TO PRESERVE BLOOD GLUCOSE LEVELS

  32. EPINEPHRINE AND GLUCAGON ARE INSULIN ANTAGONISTS • AFTER BINDING TO THEIR RECEPTORS, THEIR INTRACELLULAR SIGNALS ARE MEDIATED BY THE TRANSIENT ACTIVATION OF STIMULATORY G- HETEROTRIMERIC PROTEINS • ADENYLATE CYCLASE IS ACTIVATED • cAMP IS A “SECONDARY MESSENGER”

  33. HETEROTRIMERIC G PROTEINS MEDIATE SIGNAL TRANSDUCTION : LIGAND+RECEPTOR  HET G PROTEIN  TARGET AMPLIFICATION OF EXTRACELLULAR SIGNAL L-R COMPLEX ACTIVATES MANY HET G PROTEINS HET G PROTEINS BIND GTP AND GDP INACTIVE FORM: HET G PROTEIN + GDP ACTIVE FORM : HET G PROTEIN + GTP INACTIVE FORM + GTP  ACTIVE FORM + GDP -THIS IS AN EXCHANGE REACTION -REQUIRES LIGAND BOUND TO RECEPTOR HET G PROTEINS HYDROLYZE GTP TO GDP + Pi CAUSES DEACTIVATION OF ACTIVATED G PROTEIN A SLOW PROCESS (2 – 3 MIN-1) ACTIVATED HET G PROTEIN ACTIVATES ADENYLATE CYCLASE

  34. HETEROTRIMERIC G PROTEINS ONE OF A LARGER FAMILY OF “G PROTEINS” G PROTEINS BIND GDP AND GTP G PROTEINS HAVE GTPase ACTIVITY AMONG THEIR FUNCTIONS ARE: SIGNAL TRANSDUCTION VESICLE TRAFFICKING TRANSLATION TARGETING (SIGNAL RECOGNITION) (NOTE THAT THE GTPase ACTS AS AN “ENERGASE” AND NOT A HYDROLASE IN THESE) HETEROTRIMERIC G PROTEINS INCREASE CYCLIC AMP I.E., A SIGNAL TRANSDUCTION FUNCTION

  35. EXTRACELLULAR HORMONE RECEPTOR L B I I P L I A ADENYLATE CYCLASE D Y  E  R  GDP INTRACELLULAR GTP INACTIVE HETEROTRIMERIC G PROTEIN

  36. HORMONE-RECEPTOR COMPLEX RECEPTOR ADENYLATE CYCLASE    GTP GDP GTP-GDP EXCHANGE REACTION  ACTIVATED G PROTEIN

  37. HORMONE-RECEPTOR COMPLEX RECEPTOR ADENYLATE CYCLASE    GTP 4 ATP  4 cAMP + 4 PPi ADENYLATE CYCLASE IS ACTIVATED AND CYCLIC AMP IS PRODUCED IF THE RECEPTOR IS A “STIMULATORY” ONE

  38. HORMONE RECEPTOR ADENYLATE CYCLASE    GDP + PPi BOUND GTP IS HYDROLYZED AND AC IS DEACTIVATED

  39. G PROTEIN-COUPLED RECEPTORS • INTEGRAL MEMBRANE PROTEINS • 7 TRANSMEMBRANE HELICES • 1 % OF HUMAN GENOME CODES FOR THESE • RECEPTORS FOR • CATECHOLAMINES • EICOSANOIDS • MOST PEPTIDE AND PROTEIN HORMONES • OLFACTION AND GUSTATION • LIGHT SENSING (RHODOPSIN) • MOST IMPORTANT CLASS OF DRUG TARGETS (~ 50 % OF NEW DRUG EFFORTS)

  40. CYCLIC AMP • A “SECONDARY MESSENGER” • ATP  3’,5’- cAMP + PPi(ADENYLATE CYCLASE) • cAMP + H2O  AMP (PHOSPHODIESTERASE) • REQUIRED FOR ACTIVITY OF PROTEIN KINASE A • ALSO KNOWN AS cAMP-DEPENDENT PKA, OR cAPK • cAPK PHOSPHORYLATES SPECIFIC Ser AND/OR Thr • PHOSPHORYLASE b KINASE • GLYCOGEN SYNTHASE • cAMP PHYSIOLOGIC EFFECTS MEDIATED BY • ACTIVATION OF SPECIFIC PROTEIN KINASES

  41. CYCLIC AMP • GLUCAGON AND EPINEPHRINE   cAMP LEVELS • THIS   cAPK ACTIVITY •  cAPK ACTIVITY  •  PHOSPHORYLATION RATES •  DEPHOSPHORYLATION RATES •  PHOSPHORYLATION OF ENZYMES OF GLYCOGEN METABOLISM • GET  GLYCOGEN BREAKDOWN • WHY? • ACTIVATION OF GLYCOGEN PHOSPHORYLASE • INACTIVATION OF GLYCOGEN SYNTHASE • OPPOSITE HAPPENS WHEN [cAMP] DECREASES

  42. THE ADENYLATE CYCLASE SIGNALING SYSTEM • REFER TO THE MECHANISM OF RECEPTOR-MEDIATED ACTIVATION/INHIBITION OF AC ON PAGE 676 OF THE VOET&VOET TEXT

  43. INSULIN ACTIONS: PERIPHERAL • STIMULATES GLUCOSE UPTAKE IN • ADIPOSE TISSUE • MUSCLE • STIMULATES GLUCOSE STORAGE AS GLYCOGEN IN • LIVER • MUSCLE • STIMULATES STORAGE AS FAT IN ADIPOCYTES • PROMOTES DIFFERENTIATION OF WHITE FAT CELLS • ACTIVATES LIPOPROTEIN LIPASE • INHIBITS HORMONE-SENSITIVE LIPASE • INHIBITS GLUCONEOGENESIS IN LIVER • INHIBITS GROWTH HORMONE RELEASE • INHIBITS CATECHOLAMINES

  44. STARVATION • NORMAL DISTRIBUTION OF NUTRIENTS AFTER A MEAL • PROTEINS AMINO ACIDS IN GUT • ABSORBED BY INTESTINAL MUCOSA • PORTAL VEIN CIRCULATION TO LIVER • PROTEIN SYNTHESIS • IF EXCESS, OXIDATION FOR ENERGY • IF NOT METABOLIZED IN LIVER • PERIPHERAL CIRCULATION FOR METABOLISM • SERINE FROM RENAL GLY METABOLISM • ALANINE FROM INTESTINAL GLN METABOLISM • NO DEDICATED STORAGE FOR AMINO ACIDS

  45. STARVATIONIN-CLASS STUDY QUESTIONS • DURING STARVATION, GLUCOSE IS SYNTHESIZED FROM PROTEOLYTIC DEGRADATION OF PROTEINS (MOSTLY MUSCLE). EXPLAIN HOW THE REACTIONS OF THE GLUCOSE-ALANINE CYCLE OPERATE DURING STARVATION. WHAT KIND OF MOLECULE CAN BE CONSIDERED AS A KIND OF STORAGE DEPOT FOR AMINO ACIDS? HOW DOES IT DIFFER FROM OTHER FUEL-STORAGE MOLECULES?

  46. GLUCONEOGENESIS PHOSPHOENOLPYRUVATE ADP CO2 + GDP PYRUVATE KINASE PEP CARBOXYKINASE ATP GTP ALANINE FROM LIVER CITRIC ACID CYCLE OXALOACETATE PYRUVATE ACTIVATES ACETYL-CoA ADP + Pi ATP + CO2 PYRUVATE CARBOXYLASE CITRIC ACID CYCLE ACTIVATES

  47. STARVATION • NORMAL DISTRIBUTION OF NUTRIENTS AFTER A MEAL • CARBOHYDRATES DEGRADED IN GUT • PORTAL VEIN CIRCULATION TO LIVER • DIETARY GLUCOSE • ~1/3 CONVERTED TO GLYCOGEN IN LIVER • ~1/3 CONVERTED TO GLYCOGEN IN MUSCLE • REMAINDER OXIDIZED FOR IMMEDIATE ENERGY • GLUCOSE IN BLOOD   INSULIN • INSULIN STIMULATES: • GLUCOSE UPTAKE • GLYCOGEN SYNTHESIS: BODY STORES ~ 24 HR SUPPLY OF CARBOHYDRATE

  48. STARVATION • NORMAL DISTRIBUTION OF NUTRIENTS AFTER A MEAL • FATTY ACIDS • PACKAGED AS CHYLOMICRONS • CIRCULATED FIRST IN LYMPH AND BLOODSTREAM • NOT DIRECTLY DELIVERED TO LIVER • UPTAKE BY ADIPOSE TISSUE • TRIACYLGLYCEROLS

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