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Cardiac Muscle Metabolism
Sept. 2010KFMC-
http://www.indexedvisuals.com/scripts/ivstock/pic.asp?id=294-0048/2/2019 Cardiac Muscle Metabolism Amal Ahmed
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Heart
Main Function: Pumping of blood
Major pathway: Aerobic pathways i.ebeta oxidation and citirc acid cycle
Main substrate: Free fatty acids,lactate, ketone bodies, triglycerides,some glucose
lipoprotein lipase and respiratorychain well developed
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Skeletal Muscle Metabolism
Muscle fuel needs are dependenton activity level.
Muscle can store glycogen. Ifglucose is not available, glycogen
stores are hydrolyzed by the activemuscle.Muscle cells lack the enzymeglucose-6-phosphatase, thus,
muscle glycogen cannot supplyglucose to the circulation and othertissues.
Muscle can use both glucose and
fatty acids and occasionally evenamino acids as fuel.
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Skeletal Muscle (continued)
The resting muscle prefers fatty acids as
fuel. The active muscle undergoingrapid contraction prefers glucose.
During high activity, anaerobicrespiration ensues and glucose
metabolism produces high levels oflactate which is transported to the liver(Cori cycle).
During high activity, a large amount ofalanine is formed by transamination ofpyruvate. This is also sent to the liver(alanine) for disposal of N as urea.
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Cardiac Muscle
Heart metabolism is different fromskeletal muscle in 3 ways.Heart muscle can function only underaerobic conditions.Heart muscle cells are rich inmitochondria facilitating aerobicrespiration.Heart muscle is not able to storeglycogen.
Fatty acids are the preferred fuel of theheart. Glucose is the least favored fuel.
Ketone bodies and lactate are usedunder stress when the energy demandis high.
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The major metabolic substrates of the normal
well-oxygenated myocardium are free fattyacids in the fasted state and glucose in thefed state.
In general, the normal myocardium uses
whichever fuel is available.
During ischemia, there is a swing towardglucose metabolism and it is proposed thatglycolysis provides beneficial glycolytic ATPwhich has many protective actions, including
preservation of sodium pump activity.
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Energy Yield
The highest yield of ATP per molecule is from
fattyacids such as palmitate. This is because many of
the
carbon atoms in carbohydrates are partiallyoxidized
due to the presence of the oxygen in themolecule,
whereas fatty acid molecules contain littleoxygen
and, therefore, can yield more ATP for eachcarbon
atom.
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The disadvantage of fatty acids as a fuelis that for each molecule of ATP
produced, they require relatively moreoxygen.
Increased rates of delivery of FFAs are
potentially harmful to the ischemicmyocardium.
FFAs have oxygen-wasting potential
in the myocardium, and provision ofglucose rather than FFAs promotesrecovery in the postischemicreperfusion
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Cardiac muscle metabolismHeart failure is associated with a switch from fattyacids metabolism to glucose metabolism.
95 % of energy goes to ATP production in themitochondria.
Under severe ischemic conditions ATP degradesas follows: ATP ADT AMP adenosine (blood flow regulator)
Cellular membrane is permeable to adenosine. As
a result it is lost from the myocardium withblood flow, depleting up to of adenine basereserves during hour of ischemia. Such losscan cause cell death.
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AdenosineThe decrease in oxygen concentration in the heartcauses vasodilator substances to be released fromthe muscle cells that in turn dilate the arterioles.One of the substances which have the greatestvasodilator propensity is adenosine.
In the presence of a very low concentration ofoxygen in heart muscle, a large proportion of cell'sATP degrades to adenosine monophosphate; then asmall portion of this are further degraded to releaseadenosine into the tissue fluids of the heart muscle.
After the adenosine causes vasodilatation, much ofit is reabsorbed into the cardiac cells to be reused.Adenosine is not the only vasodilator product thathas been identified, while others include adenosinephosphate compounds, potassium ions, hydrogenions, carbon dioxide, and possibly, prostaglandins
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METABOLISM OF
THE ISCHEMIC HEART
In myocardial ischemia, myocardial cells are
suffering from a lack of oxygen, caused by
inadequate coronary blood flow.
Ischemia may be temporary and reversible, or
permanent and irreversible, leading to
myocardial infarction.
On the other hand, ischemia may also lead to
postischemic stunning, hibernation,
and preconditioning.
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Mitochondrial O2 deficit
Central to ischemia is the lack of an adequate oxygen
supply to the mitochondria (anaerobiosis), with aconsequent fall in the energy available to the cytoplasm.
The breakdown of high-energy phosphate compounds
accelerates glycolysis, pyruvate and NADH2, can enter
the mitochondria for oxidation.
The further conversion of pyruvate and NADH2 to lactate
explains the production of lactate by the ischemic
myocardium.
Direct monitoring of enhanced glycolysis in the human
ischemic myocardium can be achieved.
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Metabolic aspects of
viability of ischemic myocytes
It is proposed that an increase in glucoseuptake reflects continuing cell viability. Incontrast, decreased uptake is associated
with loss of viability of the ischemic cells,with damage progressing from reversibleto irreversible.
Cells threatened by ischemia could be
divided, according to their patterns ofglucose uptake, into those with increasedvalues (viable) or decreased values(nonviable).
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Preconditioning
A brief period of reversible ischemia beforesustained ischemia and reperfusion causescardioprotection against subsequent ischemia
This tolerance to ischemia is termed ischemicpreconditioning. The mechanisms responsible
for ischemic preconditioning are still remainunclear.
Ischemic preconditioning is:Reversible
Slowed energy utilizationReduction in myocardial necrosis
Increase protective abilities ofmyocardium
Presented as a normal proper protectivereaction of the ischemic myocardium
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Chaperones
They areabundantintracellular
proteins.Their mainfunction is
proteinfolding andtransport.
ischemic preconditioning
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Up regulation of the synthesis occurs
upon environmental stress
establishes a unique defense system
to maintain cellular protein
homeostasis and to ensure survival of
the cell.
In the cardiovascular system thisenhanced protein synthesis leads a
powerful increase in tolerance to such
endangering situations as ischemia.