5 - Lipid Metabolism

V B
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V B
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What are the three primary storage sites of a lipid in the body? Adipose Tissue The Liver Skeletal Muscle
What is the structure of a tricylclycerol (triglyceride), diacylglycerol and monoacylglycerol? Tri - 3 fatty acids Di- 2 fatty acids Mono - 1 fatty acid
What are the three types of fatty acid? Saturated Monounsaturated Polyunsaturated
How many carbon atoms are present in a 1) short chain 2) medium chain 3) long chain fatty acid? Which is most prominent? <8 8-12 >=14 Long chain.
Which three enzymes regulate lipolysis in adipose tissue and skeletal muscle? ATGL, HSL & MGL
Which enzymes regulate the entry of long chain fatty acids into the mitochondria? CPT-1 CPT-2
When fatty acids enter the mitochondria, what processes do they need to undergo in order to generate ATP? Beta oxidation (splits fatty acids into Acetyl-CoA) TCA cycle
At what intensity of exercise is fat oxidation greatest? 60-65% Vo2 max
If an athlete cycles for 4 hours at the same moderate intensity, what happens to the rate of fat oxidation? As exercise duration increases so does fat oxidation
How does the contribution of plasma fatty acids and intramuscular triglyceride to overall energy expenditure change over 2 hours of moderate intensity exercise? IMTG's are first fuels to be used Plasma free fatty acid use is delayed
What happens to the contribution of IMTG's during the first two hours of exercise? Why? Contribution decreases LCFA CoA accumulation inhibits IMTG via inhibition of HSL activity.
What do plasma fatty acids account for? Increasing reliance on fat within the first two hours.
What happens to the rate of fat oxidation if carbohydrate is ingested prior to exercise? Fat oxidation is significantly reduced with the ingestion of CHO due to an increase in insulin.
What are the main sites of regulation leading to the oxidation of fat during exercise? (5 key, 1 extra) 1) TAG lipolysis in adipose tissue 2) Fatty acid uptake into the muscle 3) IMTG lipolysis 4) Fatty acid entry into the mitochondria 5) Beta-oxidation 6) VLDL-TAG production and lipolysis
How does TAG lipolysis work? Which enzymes are key? Starts as TAG, one Fa is removed to make DAG, one FA is removed to make MAG last FA is removed to make glycerol. ATGL/HSL remove the first FA HSL removes the second FA MGL removes the third FA
What does ATGL stand for? What does HSL stand for? What does MGL stand for? Adipose triglyceride lipase Hormone sensitive lipase Monoacylglycerol lipase
What factors regulate HSL activity in the adipose tissue? (3) Adrenaline Insulin AMP concentrations
What is the process of regulating HSL called? Covalent modification via hormonal control
Describe the process of HLS regulation 1) Adrenaline binds to beta receptors 2) PKA increases leading to an increase in HSL This turns the enzyme on allowing the breakdown on FA's 3) AMPK dephosphorylates HSL (it is a negative controller) 4) Increase in insulin = a decrease in HSL
What else does the activation of HSL in adipose tissue require? Translocation to the TAG stores
What are the two processes responsible for fatty acid uptake into the muscle? 1) Diffusion 2) Protein mediated transport
How does diffusion transport fatty acids into the muscle? Increase of FA's in the bloodstream = a higher concentration outside of the muscle than in. FA's then move down the diffusion gradient
How does protein mediated transport work? FAT/CD36, FABP are found in the cell away from the membrane and need to translocate In resting conditions FAT?CD36 resides in intracellular vesicles, it must translocate to the plasma membrane to facilitate FA uptake into the muscle.
What factors regulate HSL activity in skeletal muscle during exercise? Insulin AMPk Adrenaline Calcium (from contractions)
What effect does insulin have on HSL? It inhibits HSL. It is a negative regulator
What happens to HSL after 120 minutes of exercise? Why? Decreases Levels of AMP increase through exercise activating AMPk AMPk is a negative regulator of HSL This increase in AMPk overrides adrenalines effect of HSL
When a muscle contracts, calcium is released. What does this do? Activates ERK which is a positive regulator of HSL
What does activation of HSL in skeletal muscle also require? Translocation to the TAG stores.
In terms of FA oxidation, what is the difference between a short/medium chain FA and a long chain FA. Short/medium chain FA can cross the mitochondrial membrane directly Long chain FA require a transport system.
How does a long chain FA enter the mitochondria? Fatty Acyl-CoA is joined with carnitine using CPT-1 CPT-2 then combines acyl-carnitine with free carnitine providing Acyl-CoA Acyl-CoA then enters the mitochondria
What factors regulate CPT-1 activity in skeletal muscle during exercise? Malonyl-CoA is generated to inhibit CPT-1. This is regulated by ACC (dephosphorylated in its active form) When ACC is active it stops malonyl-CoA being produced allowing FA's to enter the mitochondria.
What happens to malonyl CoA after a meal? What effect does this have on CPT-1? Insulin is increased which increases the amount of Malonyl CoA. This inhibits CPT-1
What is crucial for FA entry into the mitochondria using the CPT-1 system? Carnitine
Once the FA's are in the mitochondria how do we generate ATP? Beta-oxidation
Once the FA's are in the mitochondria how do we generate ATP? How do we regulate beta-oxidation? 1) substrate availability (acetyl CoA concentration) 2) mitochondrial redox state (NADH concentration) Beta-HAD reduces NAD+ to NADH giveing beta-ketoacyl-CoA Too much NADH stops NAD+ converting resulting in a decrease of beta-oxidation
How many carbons are used to transform fatty acetyl-CoA to acetyl CoA? If we have a 16 carbon FA, how many times will we make acetyl CoA? 2 8
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