energy metabolism in muscle Flashcards
the main types of fuel used by muscle for energy metabolism are what?
glycogen
glucose
free fatty acids
what does muscle use predominantly at rest?
fatty acids
what does muscle use during high intensity isometric exercise?
anaerobic glycolysis
creatine kinase reaction
during low intensity submaximal exercise, the main sources of energy are ….
blood glucose and free fatty acids
with high intensity submaximal exercise what happens to the proportion of energy derived from glycogen and glucose?
it is increased, glycogen becomes the main sources
when does fatigue happen?
when glucose and glycogen stores are depleted
during the first hour of mild, low intensity exercise (jogging) what is the major source of energy ?
glucose
glucagon
free fatty acids
the uptake of free fatty acids by muscle increases when?
during one to four hours of mild to moderate prolonged exercise
what happens after four hours of exercise?
lipid oxidation becomes the major source of energy
muscle contraction and relaxation depend primarily on what
hydrolysis of ATP
when does anaerobic glycolysis occur usually
during conditions of high intensity, sustained isometric muscular activity (lifting heavy objects)
particularly in the setting of limited blood flow and oxygen supply to exercising muscle fibers
increased concentrations of lactate within muscles, and the accumulation of Pi, ADP and movovalent form of organic phosphate are related to what?
fatigue
aerobic glycolysis is important when?
during dynamic forms of exercise, such as walking, running.
what is the main source of energy is muscle and other cells?
oxidative phosphorylation
this system produces 17-18 times as much adenosine triphosphate from the same amount of glucose
when is the phosphocreatine pathway utilized?
during very high intensity exercise
what is the process of the phosphocreatine pathway?
rapid formation of ATP can be accomplished through the reaction of phosphocreatine with ADP, catalyzed by creatine kinase
this is very BRIEF b/c of small amount of phosphocreatine in the muscle
where is creatinephosphate synthesize and subsequently transported?
synthesized in the liver and transported to the muscle cells via the bloodstream
for storage in skeletal muscle and the brain
when can creatine phosphate donate a phosphate group to ADP to form ATP?
during the first 2-7 seconds following an intense muscular or neuronal effort
what does ATP derived from creatininephosphate supply?
immediate short bursts of contractile energy
high jumps, sprints, etc
what can you do with excess ATP during a period of low effort ?
convert to creatininephosphate making an energy reservoir for rapid buffering and regeneration of ATP
what organs can you find creatine kinase in?
heart
brain
lung
skeletal muscle
where do you find CK1 (aka CK-BB)
brain
smooth muscles
lungs
CK-2 is found where? aka CK-MB
mostly in the heart
CK3- aka CK-MM is found where?
mostly in skeletal muscle
CK is assayed in blood tests and an elevation of CK is an indication of what?
myocardial infarction
rhabdomyolysis (severe muscle breakdown)
muscular dystrophy, myasthenia gravis, myositis
acute renal failure
drugs (statins, anticoagulants, aspirin, cocaine, etc.)
what is the purine nucleotide cycle ?
intensely exercising muscle can generate ATP over a short period of time using adenylate kinase reaction
this reaction catalyzes the conversion of two ADP molecules into one molecule of ATP and AMP
this cycle tries to catch up with insufficient ATP supply by converting ADP to ATP
2ADP–> ATP–> AMP—> IMP–> NH3
what is a cause of metabolic myopathy?
AMP deaminase converts AMP to IMP and releases an NH3 molecule in the process
deficiency of AMP deaminase is apparently a cause that is common of exercise-induced myopathy and metabolic myopathy
lipid metabolism in muscle occurs via what?
beta and omega oxidation of fatty acids
long chain fatty acids constitute a major source of energy for what?
prolonged low intensity exercise, lasting for more than 40-50 minutes
the mitochondrial membrane is not permeable to long-chain fatty acids so what must happen?
a multistep process
in cytoplasm–> long chain fatty acids are first activated by long-chain acyl-CoA synthetase to their CoA thioesters
CoA thioesters then linked with carnitine by the enzyme Carnitin palmitoyltransferase (CPT I)
this is now acylcarnitine and is transferred across the inner mitochondrial membrane by carnitine;acylcarnitine transferase
once in the mitochondrial matrix it is converted back to free acyl-CoA derivative and carnitine by CPT II
the long chain acyl-CoA enters the beta-oxidation pathway
what happens to 95 percent of Acetyl-Coa that is hepatic ?
it is converted to ketones which are important sources of energy for all tissues, particularly the brain
during prolonged fasting ketones provide an important source of energy in brain tissue because the BBB is impermeable to long chain fatty acids
what is omega-oxidation of fatty acids ?
during prolonged fasting 20 percent of total cellular oxidation of fatty acids is accomplished in liver peroxisomes through omega-oxidation
producing DCA’s (dicarboxylic acids)
what is different about peroxisomes?
beta oxidation occurs via a flavin-containing oxidase that generates H2O2, and then through peroxisomal catalase H20 and O2, therefore some energy is wasted
in metabolic defects of intramitochondrial fatty acid oxidation what is going on?
mitochondrial beta-oxidationof DCA’s is impaired at a time when the production of DCA’s is increased due to the recruitment of peroxisomal omega-oxidation, hence FINDING OF DCA”S IN THE URINE
what is a useful marker of diagnosing inborn errors of fatty acid oxidation?
detection of acylcarnitine derivatives in serum and the detection of dicarboxylic acids and acylglycines in urine
what is the cori cycle?
recycling of lactic acid
cori cycle operates more efficiently when the muscular activity has stopped
in muscle glucose–> pyruvate–> lactate
lactate then goes to the liver
lacate–> pyruvate – > glucose
glucose goes back to muscle via blood
what is the significance of the cori cycle?
the prevention of lactic acidosis in the muscle under anaerobic conditions
the conversion of lactate to pyruvate provides about 30 percent of the glucose for gluconeogenesis in liver
what makes lactate
lactate dehydrogenase
in exercising skeletal muscle what happens when NADH production exceeds the oxidative capacity of the respiratory chain?
this results in elevated NADH/NAD+ ratio, favoring reduction of pyruvate to lactate
THEREFORE during intense exercise, lactate accumulates in muscle causing a drop in intracellular pH, resulting in CRAMPS
how does the ratio of NADH/NAD+ in the liver and heart compare to exercising muscle?
the ratio is lower in heart and liver
what does the liver convert pyruvate into ?
glucose by gluconeogenesis or oxidized in the TCA cycle
what does the heart excluseivley oxidize lactate to?
CO2 and H20 via the TCA cycle
what is lactic acidosis ?
elevated concentrations of lactate in the plasma
occurs whemn there is a myocardial infarction, PE, uncontrolled hemorrhage, or when an individual is in shock
the failure to bring adequate amounts of oxgyen to the tissues results in impaired oxidative phophorylation and decreased ATP synthesis
to survive the cell relies on anaerobic glycolysis which prodcuces lactic acid as end product
elevated muscle lacate accounts for what?
fatigue and pain induced by strenuous exercise
how is NAD+ regenerated in anaerobic conditions?
NAD+ is regenerated by further metabolism of pyruvate
electrons are transferred from NADH to pyruvate by lactate dehydrogenase forming NAD+ and lactate
what are the symptoms of metabolic myopathy
exercise intolerance
muscle pain and cramps
what are some causes of metabolic myopathies?
carnitine deficiency syndrome
fatty acid transport defects
defects of beta-oxidation enzymes
what is a primary carntitine deficiency
lack of carnitine in the cell (such as a mutation in the carnitine transporter) and is associated with lipid myopathy
fatty acid oxidation is significantly reduced
DON”T SEE elevated levels of acyl carnitine
what is a secondary carnitine deficiency
occurs when the carnitine is sequestered in the form of acyl-carnitine (carnitine cannot be removed from acyl group, such as defects in carnitine acyl transferase 2)
WOULD SEE ELEVATED levels of ACYL CARNITINE fatty acid oxidation is significantly reduced
fatty acids can only be used in
aerobic metabolism
