CONTROL OF INTERMEDIARY METABOLISM D C MIKULECKY Dept

CONTROL OF INTERMEDIARY METABOLISM D. C. MIKULECKY Dept. Physiology

ENERGY IS CAPTURED BY PLANTS CO 2 + H 2 O + RADIANT (SOLAR ) ENERGY --> (CH 20)n + O 2

ANAEROBIC METABOLISM z SUGAR CAN BE BURNED WITHOUT OXYGEN - ANAEROBICALLY z FAR MORE ENERGY RELEASED FROM BURNING SUGAR AEROBICALLY z GLYCOLYSIS IS ANAEROBIC-CARRIED OUT IN CYTOSOL z GLUCOSE ----> 3 CARBON FRAGMENTS PLUS 2 ATP

AEROBIC METABOLISM z PYRUVIC ACID (3 C FRAGMENT) ENTERS MITOCHONDRIA z COMBINES WITH COENZYME A LOOSING A CO 2 AND BECOMING ACETYL COENZYME A (2 C FRAGMENT) z THIS FRAGMENT ENTERS A CYCLIC REACTION SCHEME, THE CITRIC ACID CYCLE, ATP IS PRODUCED z PRODUCTS OF THE CITRIC ACID CYCLE ENTER THE ELECTRON TRANSPORT CHAIN, MORE ATP IS PRODUCED BY OXIDATIVE PHOSPHORYLATION z ULTIMATELY, 34 MORE ATP’S ARE PRODUCED

MITOCHONDRIA z. Extract Energy from Food Fuels z. Energy is stored in ATP z. Aerobic Metabolism

OVERVIEW OF CATABOLISM DIETARY PROTEIN DIETARY CARBOHYDRATES DIETARY FATS AMINO ACIDS GLUCOSE FATTY ACIDS MITOCHONDRIA ACETYL-COA CAC ELECTRON TRANSPRT CHAIN ATP

OVERALL REGULATION OF BLOOD GLUCOSE (+) RELEASE FROM LIVER - ( ) BLOOD GLUCOSE INSULIN (+) EPINEPHRINE AND NOREPINEPHRIN (+) GLUCAGON GLUCOCORTICOIDS - ( ) CONSUMPTION BY MUSCLE AND FAT CELLS - ( ) GH

SYNERGISTIC EFFECTS OF CORTISOL, GLUCAGON, AND EPINEPHRINE ON BLOOD GLUCOSE z. WHEN ALL THREE ARE PRESENT THE EFFECT IS FAR MORE THAN ADDITIVE z. COUNTERREGULATORY HORMONES z. ALSO GH AND T 3

HYPOGLYCEMIA (LOW BLOOD SUGAR) z. HYPOPITUITARYISM z. ADRENAL CORTICAL FAILURE (ADDISON’S DISEASE) z. SEVERE HEPATIC DAMAGE

METABOLIC ACTIONS OF GROWTH HORMONE z. MOBILIZES TRIGLYCERIDE FAT STORED IN ADIPOSE TISSUE z. CONSERVES GLUCOSE FOR BRAIN

THYROID HORMONE’S EFFECTS z METABOLIC RATE: INCREASED BMR z CALOROGENIC: INCREASED HEAT PRODUCTION z SYMPATHOMIMETIC: FLIGHT OR FIGHT z CARDIOVASCULAR: INCREASES RESPONSIVENESS OF HEART z GROWTH: ESSENTIAL FOR NORMAL GROWTH z NERVOUS SYSTEM: DEVELOPMENT AND ADULT ACTIVITY

ACTIONS OF EPINEPHRINE z. MIMICS SYMPATHETIC NS z. MOBILIZES STORED FAT AND CARBOHYDRATE z. HEART AND BLOOD VESSELS

GENERAL ADAPTATION SYNDROME z. FLIGHT OR FIGHT z. EPINEPHRINE z. CRH-ACTH-CORTISOL z. RENIN-ANGIOTENSIN-ALDOSTERONE z. VASOPRESSIN z. COORDINATED BY HYPOTHALAMUS z. CAN BE INDUCED PSYCHOSOCIALLY

FEEDING : INSULIN y. CEPHALIC PHASE: INSULIN y. FOOD IN SMALL INTESTINE: GIP - A SECRETAGOUGE FOR INSULIN y. INCREASED GLUCOSE AND AA IN BLOOD STIMULATE INSULIN SECRETION y. BLOOD INSULIN MAY SWING AS MUCH AS FROM 10 TO 50 MICROUNITS/ML y. MOVES ABSORBED SUGAR AND FAT TO STORES

SEVERAL HOURS AFTER EATING ABSORPTION FROM S. I. COMPLETE INSULIN SECRETION RETURNS TO LOW BASAL RATES BEGIN TO DRAW UPON STORES OF FUEL BLOOD GLUCOSE RETURNS TO ABOUT 5 MMOL/L. GLUCAGON, GH, ADRENAL HORMONES ALSO SECRETED AT LOW BASAL RATES z ABOUT 75% GLUCOSE CONSUMED BY BRAIN, BLOOD CELLS, OTHER TISSUES NOT DEPENDENT ON INSULIN, THE OTHER 25% BY MUSCLE AND ADIPOSE TISSUE. MAY BEGIN SOME GLUCONEOGENESIS IN LIVER z z z

FASTING z. AFTER 24 HOURS WITHOUT FOOD FASTING BEGINS z. INSULIN DECREASES FURTHER, GLUCAGON AND GH INCREASE, CORTISOL FOLLOWS ITS USUAL DIURNAL RHYTHM z. FATTY ACID MOBILIZATION IS SPED UP

TURNOVER OF SUBSTRATES DURING FAST: FUEL RESERVES

TURNOVER OF SUBSTRATES DURING FAST: CONSUMPTION

PROLONGED FASTING (3 DAYS OR MORE) z KETONE BODIES REACH 2 TO 3 MMOL/L z BECOME SIGNIFICANT PART OF BRAIN’S FUEL ALONG WITH GLUCOSE z INHIBIT PROTEIN BREAKDOWN IN MUSCLE z URINARY NITROGEN EXCRETION DECREASES (ONLY ENOUGH GLUCONEOGENESIS FOR THE BRAIN)

STARVATION z. URINARY NITROGEN AGAIN INCREASES z. ONCE FAT AND/OR TRIGLYCERIDE RESERVES ARE DEPLEATED

FASTING BLOOD LEVELS