Biochem - metabolic profile of muscle Flashcards
What type of fibers are slow, oxidative?
Type I- red fibers- produce most ATP aerobically- slow to fatigue- maintain prolonged low-intensity contractions
(ex. psoas major- virtually all red fibers) - slow contraction speed - Marathon runners - Endurance
What type of fibers are fast oxidative glycolytic?
Type IIa - white fibers - produce most ATP by anaerobic glycolysis- fatigue rapidly - employed in rapid, powerful contractions over shorter periods - Sprinters -
What types of fibers are fast glycolytic?
Type IIb - red fibers - intermediate - can produce ATP by both methods - prevalent in muscles involved in regular movement -
What type of energy production is there in cardiac muscle?
What is the preferred substrate?
- Aerobic metabolism, contains many mitochondria and allot of myoglobin. Can use (fatty acids, glucose, ketone bodies, lactate)
Fatty acids are the preferred substrate
Where is most of the energy for smooth muscle obtained from?
- Glycolysis - therefore less oxidative capacity than cardiac muscle
What is the initial requirement of ATP for contraction supplied by?
- creatine
What is the only energy source that changes greatly in concentration during a muscle contraction?
AMP - its levels rise very quickly and activates glycogenolysis (via phosphorylase b) and glycolysis (via PFK-1)
How does creatine kinase work?
What is the rate that it is broken down?
It removes a phosphate from phosphocreatine and adds it to ADP forming ATP and Creatine.
- The breakdown of creatine phosphate to creatine is at the same rate no matter what activity level you are doing.
What does ADP and Ca2+ ions activate?
- ADP activates: TCA
- Ca2+ activates glycogenolysis, TCA,
How is there replenishment of ATP when muscle contracts
can occur via glycogen breakdown stimulation from AMP, Ca 2+-calmodulin, or protein kinase A.
How does glycogen breakdown occur?
- phosphorylase b changes to phosphorylase a which can occur by:
1) AMP
2) Ca2+
3) Epinephrine during times of stress
What is the deficiency and the physiological results with McArdle’s Disease?
- deficiency (genetic) of muscle glycogen phosphorylase leading to a defect in glycogen breakdown. Symptoms are painful muscle cramps and unusual fatigue on exercise and an inability to produce lactate during exercise.
What is the replaced mechanism of energy production during vigourous exercise in McArdle’s?
Rhabdomyolysis
What is primarily responsible for initial activation of PFK-1?
AMP
What parts of the TCA cycle do Ca2+ activate? What parts do ADP activate?
- Ca2+ activates:
1) pyruvate dehydrogenase
2) isocitrate dehydrogenase
3) alpha-oxoglutarate dehydrogenase - ADP activate
1) isocitrate dehydrogenase
How can Glut 4 transporters be increased or decreased?
- high glucose levels –> increased insulin levels–> increase in glut 4 movement to cell membrane–> increased glucose transport to cell
- dec glucose–>dec insulin –> glut 4 transportes removed from surface of the cell
What is the main limiting factor in the amount of glycogen stored in muscles?
The amounts of glycologen, the excess glucose is converted to fat
What are the main site of BCAA metabolism?
- Skeletal muscles
What are the main type of metabolism that is used to produce energy in type IIb fibers?
- Produced by lactate produced by anaerobic glycolysis, and glycogen can be mobilized for rapid release of metabolic substrate
What types of energy do types I and IIa fibers use?
- most energy produced by oxidative metabolism.
What are the advantages of carbohydrate over fat?
- its catabolism can be switched on faster, maximum rate of ATP formation is greater, yields of ATP per oxygen molecule is greater
What is the major disadvantage of carbohydrate usage?
- produces about 7 times less energy per gram
What is oxygen debt?
- The continued consumption of oxygen after vigorous sustained exercise is over and is due to increasing lactate.
What is the main contributor to muscle fatigue?
- Increase in Pi (major contributor)
- Fall in pH (inhibits PFK-1, inhibits release of Ca2+)
- Neuromuscular
- Central fatigue
Where are the sources of energy for type I and IIa (red) fibers?
catabolize glucose and fats
- source of fats (triacylglcerols- from VLDL and chylomicra, and from free fatty acids)
What do Red fibers have a higher level of (as opposed to white fibers) reflecting their greater emphasis on oxidative metabolism?
higher levels of FABP and LPL
When blood glucose rises, what does it switch on and what is stopped from releasing fat.
- insulin is switched on and lipoprotein lipase is stopped from releasing fat.
ACC-2 converts acetyl CoA to malonyl CoA which inhibits the uptake of fats by the mitochondria, why do you have a fat synthesis enzyme present in a tissue that don’t metabolize fat.
-AMP-PK inhibits ACC-2 that mediates Acetyl CoA conversion to Malonyl CoA
How is Fatty acid uptake into mitochondria regulated?
- AMP stimulates the uptake of fatty acids into the mitochondria by stimulating AMP-PK which inhibits ACC-2 (which would cause Acetyl CoA–>Malonyl CoA) and postively stimulate MCoADC which changes Malonyl CoA (which would normally block Acetyl CoA uptake
What are the main sources of energy during starvation for:
the brain
Muscle:
the brain and rbc- glucose
Muscle: fatty acid and ketone bodies
During starvation what amino acids are released from the liver
glutamine and alanine
Where does glucagon activate glycogen phosphorylase?
Glucagon activates glycogen phosphorylase in the liver NOT THE MUSCLES
After 4 hours of starvation what are the main source of fuels?
After 3 weeks what is the main source of fuels?
- Fatty acids
- ketone bodies and fatty acids
When is breakdown of muscle protein to provide C atoms for gluconeogenesis (liver) rapid when?
What is it stimulated by?
- days 1-2
- Stimulated by Cortisol
What is excess acetyl CoA converted into?
Acetoacetate and Beta hydroxybutyrate and acetone
In the fed state what are the percentages of fatty acid usage and glucose usage of the cardiac muscle?
- Fatty acids: 60-90% and Glucose: 10-40%
What are the 2 sources of energy in the fasted state?
Fatty acids and ketone bodies
What occurs in the cardiac muscle during ischemic conditions in the cardiac muscle?
- AMP activates AMP-activated protein kinase that phosphorylates PFK-2 (activating it) which enhances production of fructose 2,6 bisphosphate which activates PFK-1
