CONTROL OF INTERMEDIARY

METABOLISM

D. C. MIKULECKY
Dept. Physiology
 ENERGY IS CAPTURED BY
PLANTS

CO2 + H2O + RADIANT (SOLAR ) ENERGY --> (CH20)n + O2

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 ----> 3 CARBON FRAGMENTS
PLUS 2 ATP
 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 ATP’S ARE PRODUCED
 MITOCHONDRIA
 Extract Energy from Food Fuels

 Energy is stored in ATP

 Aerobic Metabolism
OVERVIEW OF CATABOLISM

DIETARY DIETARY DIETARY

PROTEIN CARBOHYDRATES FATS

AMINO ACIDS GLUCOSE FATTY ACIDS

MITOCHONDRIA
ELECTRON
ACETYL-
CAC TRANSPRT ATP
COA
CHAIN
OVERALL REGULATION OF
BLOOD GLUCOSE
RELEASE
(+)
EPINEPHRINE
FROM LIVER
(-)
(+) AND
NOREPINEPHRIN

BLOOD (+) GLUCAGON

INSULIN GLUCOSE GLUCOCORTICOIDS

-
( )
(+)
-
( ) GH
CONSUMPTION
BY
MUSCLE AND FAT CELLS
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
 HYPOGLYCEMIA
(LOW BLOOD SUGAR)

 HYPOPITUITARYISM
 ADRENAL CORTICAL FAILURE
(ADDISON’S DISEASE)
 SEVERE HEPATIC DAMAGE
METABOLIC ACTIONS OF
GROWTH HORMONE

 MOBILIZES TRIGLYCERIDE FAT STORED

IN ADIPOSE TISSUE
 CONSERVES GLUCOSE FOR BRAIN
THYROID HORMONE’S EFFECTS

 METABOLIC RATE: INCREASED BMR

 CALOROGENIC: INCREASED HEAT PRODUCTION
 SYMPATHOMIMETIC: FLIGHT OR FIGHT
 CARDIOVASCULAR:INCREASES RESPONSIVENESS OF
HEART
 GROWTH: ESSENTIAL FOR NORMAL GROWTH
 NERVOUS SYSTEM:DEVELOPMENT AND ADULT
ACTIVITY
ACTIONS OF EPINEPHRINE

 MIMICS SYMPATHETIC NS
 MOBILIZES STORED FAT AND
CARBOHYDRATE
 HEART AND BLOOD VESSELS
GENERAL ADAPTATION
SYNDROME

 FLIGHT OR FIGHT
 EPINEPHRINE
 CRH-ACTH-CORTISOL
 RENIN-ANGIOTENSIN-ALDOSTERONE
 VASOPRESSIN
 COORDINATED BY HYPOTHALAMUS
 CAN BE INDUCED PSYCHOSOCIALLY
 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
 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
 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
 TURNOVER OF SUBSTRATES
DURING FAST: FUEL RESERVES

MUSCLE: PROTEIN 75 g
ADIPOSE TISSUE : 160 g + 16 g
FA + GLYCEROL
LIVER: GLYCOGEN 180 g
 TURNOVER OF SUBSTRATES
DURING FAST: CONSUMPTION

NERVE 144 g
RBC, WBC, ETC. 36 G
HEART, KIDNEY, 180 g
MUSCLE, ETC.
 PROLONGED FASTING
(3 DAYS OR MORE)

 KETONE BODIES REACH 2 TO 3 MMOL/L

 BECOME SIGNIFICANT PART OF BRAIN’S
FUEL ALONG WITH GLUCOSE
 INHIBIT PROTEIN BREAKDOWN IN
MUSCLE
 URINARY NITROGEN EXCRETION
DECREASES (ONLY ENOUGH
GLUCONEOGENESIS FOR THE BRAIN)
 STARVATION

 URINARY NITROGEN AGAIN

INCREASES

 ONCE FAT AND/OR TRIGLYCERIDE

RESERVES ARE DEPLEATED
 FASTING BLOOD LEVELS
SAMPLING GLUCOSE INSULIN GLUCAGON CORTISOL GH T3
TIME Mg/dL Mu/mL pg/Ml ng/mL ng/mL ng/mL

POST- 150 50 120 <1 1.2

PRANDIAL

POST- 90 15 100 120 2 1.15

ABSORPTIVE

DAY 1 80 10-12 120 120 2 1.15

DAY 2 70 8 150 110 6 0.70

DAY 3 70 7 150 110 10 0.60