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OTHER REGULATOR OF HEARTMETABOLISM

1. Arterial substrate2. Hormone level3. Coronary flow4. Inotropic state5. Nutritional status of the tissue

How many ATP is produced in well-perfusedhuman heart? (post absorptive state)

Fatty acid 60-80 % ATPGlucose 10-30 % ATPLactate 10-30 % ATP

Ketone bodies Very low in nondiabetic

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FATTY ACID OXIDATION IN HEARTFatty acid oxidation depends on concentrationof plasma fatty acid.Concentration of plasma fatty acid dependson lipolysis.Lipolysis :- Stimulated Noradrenaline and

adrenaline- Inhibited Insulin- (if insulin is low, lipolysis will be activated

#diabetics are thin)Once fatty acid enters the cell, it becomesfatty acyl coA

It is either:1. oxidized in mitochondria

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CARBOHYDRATE METABOLISM3 sources of carbohydrate fuel:

1. Extracellular glucose2. Extracellular lactate3. Glycogen stores

Regulated by transmembrane glucosegradient and conc. of glucose transporter(GLUT 1 and GLUT 4)3 I increases the capacitance of GLUT :

1. Ischemia2. Insulin3. Increase work demand

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RANDLE CYCLEStates that: High rate of fatty acid oxidationinhibit uptake and oxidation of glucose andlactate by heart.Key irreversible step: (decarboxylation)Pyruvate (glucose) acetyl CoA (fatty

acid)pyruvate dehydrogenase (PDH).

PDH:

Activation InhibitionPDH Phosphatase by

dephosphorylation

(more pyruvate oxidation)

PDH Kinase byphosphorylation (less

pyruvate oxidation)- Acetyl CoA/CoA ratio- NADH/NAD+ ratio - Fatty acid and ketone

bodies oxidation

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METABOLISM

In general, insulin causes heart to take up and

oxidize more glucose and lactate by 2 mech:Direct mechanism:- stimulate GLUT 1 and GLUT 4 incorporation

(more glucose enters cell )- stimulate hexokinase and glycogensynthethase ( glycogen storage )Indirect mechanism:

- From fatty acid oxidation, we know insulininhibit lipolysis. So free fatty acid level will below.

- From Randle Cycle, we know low free fattyacid level will increases glucose and lactateoxidation. (the inverse relation)

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CARDIAC ENZYMEWait for 4 hours after onset of chest pain, before

taking blood sample.NAME TYPES STARTS TORISE

(HOURS)

MISCELLANEOUS

MYOGLOBIN

LMW Haemcontaining protein

2-4 -Early diagnosis of acute MI- Not cardiac specific-Present in cardiac andskeletal muscle

CREATINEKINASE

CKMM, CKBB,CKMB, CKMB 1,CKMB 2.

4-6 -Present in muscle andbrain-CKMM appear first, longerhalf life. Could be due torecent IM, surgery orexercise-Prolonged rise CKMM:

cardiac ventricularaneur sm

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ASPARTATETRANSAMINASE

(AST)

Risessignificantly lessthan

CKMB

6-8 -Hepatic congestion due to rightsided heart failure-Primary hepatic dysfunction AST while LDH normal

-Present in cardiac and sk muscleTROPONIN

TnC, TnI,TnT

4-6 -Troponin is muscle regulator-Remains for 7-10 days (latepresentation of chest pain)-TnC: no struc diff btw sk and card

muscle-TnI & TnT: diff struc. Sensitive tooccult myocard infarction-TnI: subject to proteolysis-TnT: chronic renal failure, remainslonger-Increase in subarachnoid hemorrhage

LACTATEDEHYDROGENASE

5isoenzymes

12-24 -Late enzyme-Present in cardiac and skeletal muscle

-Isoenzyme 1 specific in heart-To know which isoenzyme increase,

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Questions1. What is the effect of fatty acid oxidation to pyruvateoxidation according to Randle Cycle.2. Enumerate how many ATP is produced by fatty acid(%)3. Enumerate 3 sources of CHO fuel in CHOmetabolism.4. Enumerate 3 factors increasing GLUT capacitance5. Resynthesis of ATP occur by what ways?6. In general, what does insulin do to heartmetabolism?7. What is the key irreversible step in Randle Cycle?8. Enumerate factors stimulating PDH and inhibitingPDH9. Enumerate factors stimulating lipolysis and