CONTROL OF INTERMEDIARY METABOLISM

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CONTROL OF INTERMEDIARY METABOLISM

• D. C. MIKULECKY
• Dept. Physiology

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ENERGY IS CAPTURED BY PLANTS
CO2 H2O RADIANT (SOLAR ) ENERGY --gt
(CH20)n O2
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ANAEROBIC METABOLISM

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

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AEROBIC METABOLISM

• PYRUVIC ACID (3 C FRAGMENT) ENTERS MITOCHONDRIA
• COMBINES WITH COENZYME A LOOSING A CO2 AND
  BECOMING ACETYL COENZYME A (2 C FRAGMENT)
• THIS FRAGMENT ENTERS A CYCLIC REACTION SCHEME,
  THE CITRIC ACID CYCLE, ATP IS PRODUCED
• PRODUCTS OF THE CITRIC ACID CYCLE ENTER THE
  ELECTRON TRANSPORT CHAIN, MORE ATP IS PRODUCED BY
  OXIDATIVE PHOSPHORYLATION
• ULTIMATELY, 34 MORE ATPS ARE PRODUCED

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MITOCHONDRIA

• Extract Energy from Food Fuels
• Energy is stored in ATP
• Aerobic Metabolism

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OVERVIEW OF CATABOLISM
DIETARY CARBOHYDRATES
GLUCOSE
MITOCHONDRIA
ELECTRON TRANSPRT CHAIN
ACETYL-COA
ATP
CAC
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OVERALL REGULATION OF BLOOD GLUCOSE
()
RELEASE FROM LIVER
EPINEPHRINE AND NOREPINEPHRIN
()
(-)
()
GLUCAGON
BLOOD GLUCOSE
INSULIN
GLUCOCORTICOIDS
(-)
()
(-)
GH
CONSUMPTION BY MUSCLE AND FAT CELLS
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SYNERGISTIC EFFECTS OF CORTISOL, GLUCAGON, AND
EPINEPHRINE ON BLOOD GLUCOSE

• WHEN ALL THREE ARE PRESENT THE EFFECT IS FAR MORE
  THAN ADDITIVE
• COUNTERREGULATORY HORMONES
• ALSO GH AND T3

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HYPOGLYCEMIA(LOW BLOOD SUGAR)

• HYPOPITUITARYISM
• ADRENAL CORTICAL FAILURE (ADDISONS DISEASE)
• SEVERE HEPATIC DAMAGE

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METABOLIC ACTIONS OF GROWTH HORMONE

• MOBILIZES TRIGLYCERIDE FAT STORED IN ADIPOSE
  TISSUE
• CONSERVES GLUCOSE FOR BRAIN

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THYROID HORMONES EFFECTS

• METABOLIC RATE INCREASED BMR
• CALOROGENIC INCREASED HEAT PRODUCTION
• SYMPATHOMIMETIC FLIGHT OR FIGHT
• CARDIOVASCULARINCREASES RESPONSIVENESS OF HEART
• GROWTH ESSENTIAL FOR NORMAL GROWTH
• NERVOUS SYSTEMDEVELOPMENT AND ADULT ACTIVITY

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ACTIONS OF EPINEPHRINE

• MIMICS SYMPATHETIC NS
• MOBILIZES STORED FAT AND CARBOHYDRATE
• HEART AND BLOOD VESSELS

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GENERAL ADAPTATION SYNDROME

• FLIGHT OR FIGHT
• EPINEPHRINE
• CRH-ACTH-CORTISOL
• RENIN-ANGIOTENSIN-ALDOSTERONE
• VASOPRESSIN
• COORDINATED BY HYPOTHALAMUS
• CAN BE INDUCED PSYCHOSOCIALLY

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FEEDING INSULIN

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

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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
• 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

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FASTING

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

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TURNOVER OF SUBSTRATES DURING FAST FUEL RESERVES
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TURNOVER OF SUBSTRATES DURING FAST CONSUMPTION
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PROLONGED FASTING (3 DAYS OR MORE)

• KETONE BODIES REACH 2 TO 3 MMOL/L
• BECOME SIGNIFICANT PART OF BRAINS FUEL ALONG
  WITH GLUCOSE
• INHIBIT PROTEIN BREAKDOWN IN MUSCLE
• URINARY NITROGEN EXCRETION DECREASES (ONLY ENOUGH
  GLUCONEOGENESIS FOR THE BRAIN)

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STARVATION

• URINARY NITROGEN AGAIN INCREASES
• ONCE FAT AND/OR TRIGLYCERIDE RESERVES ARE
  DEPLEATED

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FASTING BLOOD LEVELS