AMPK and AMP Sensors Flashcards
(52 cards)
What is the point of metabolic research?
Better and more personalized treatments
Because T2D and obesity pandemic is getting worse
What are some flaws of current metabolic treatments?
Current treatments are efficacious but lack durability and have side effects
What groups of people is T2D difficult to treat?
Younger people
Ethnic minorities
What are two fuels in non-muscle stores?
Liver glycogen»_space;> plasma glucose
Adipose tissue triacylglycerol»_space;> plasma fatty acids
What fuels are available to muscle (in fit, healthy males)
There are intramuscular stores of glycogen and triacylglycerol
Both of which get converted into ATP by the mitochondria
How are fatty acids broken down in mitochondria during exercise?
In muscle cell, FA need to enter mitochondria = inner mitochondrial membrane is impermeable to fatty acids, so they require a transport mechanism.
Fatty acids are first activated in the cytoplasm by acyl-CoA synthetase = attaching to Coenzyme A (CoA) to form fatty acyl-CoA.
Fatty acyl-CoA = transported into the mitochondria with the help of a carrier protein called the carnitine shuttle.
This shuttle involves:
Carnitine palmitoyltransferase I (CPT1), which converts fatty acyl-CoA to acylcarnitine, allowing it to pass through the outer mitochondrial membrane.
Once inside the mitochondria, CPT2 on the inner membrane converts the acylcarnitine back to fatty acyl-CoA.
What is the cartinine shuttle and its function?
Fatty acyl-CoA = transported into the mitochondria with the help of a carrier protein called the carnitine shuttle.
This shuttle involves:
Carnitine palmitoyltransferase I (CPT1), which converts fatty acyl-CoA to acylcarnitine, allowing it to pass through the outer mitochondrial membrane.
Once inside the mitochondria, CPT2 on the inner membrane converts the acylcarnitine back to fatty acyl-CoA.
What is the correlation between mobilization and depletion of fuels?
Fuels that can be mobilized most rapidly are also the most short-lived
The larger the estimated maximum rate of ATP generated = shorter estimated time of complete depletion
What fuels have the highest estimated max rate of ATp generation (and thus quicker depletion time)
Muscle phosphocreatine
Muscle glycogen when converted to lactate
Muscle glygogen to CO2
Blood glucose to CO2
Blood fatty acids to CO2
Where is blood glucose mainly derived from?
Liver glycogen breakdown
Where is blood fatty acids mainly derived from ?
Adipose tissue triacylglycerol breakdown
What enzyme generates phosphocreatine?
Mitochondrial creatine kinase (mi-CK)
What is phosphocreatine generated from?
ATP by mitochondrial creatine kinase
Where does phosphocreatine diffuse to after being made in the mitochondria?
Diffuses to myofibril, where it is then converted to creatine and ATP by “muscle” isoform of creatine kinase (M-CK)
Once ATP is hydrolysed for muscle contraction = creatine diffuses back to mitochondria
What is the role of phosphocreatine?
Energy carrier
Transports energy (ATP) from the site of production (mitochondria) to side of consumption (myofibril)
What exercise does phosphocreatine help with?
Sustain intense, brief contractions
From rest to about 50% maximum intensity what fuels are mainly used?
Fatty acids and triacylglycerol
Fats are an abundant, rich store of energy
Why at higher intensities of exercise does fuel usage shift to glucose and glycogen?
Because amount of ATP generated per molecule of oxygen used is higher for glucose htan fatty acids
At higher exercise intensities = rate of oxygen delivery to muscle becomes LIMITING FACTOR
At higher exercise intensities, what are the rate limiting factors?
Rate of oxygen supply
Rate of glucose uptake
So breakdown of glycogen IN MUSCLE is important
Where are the two carnitine:palmitoyl-CoA transferases found?
CPT1 = outside inner mitochondrial membrane
CPT2 = inside inner mitochondrial membrane
What inhibits CPT1?
Malonyl-CoA
What happens to malonyl-CoA during exericse?
Malonyl-CoA decreases in muscle during exercise
Could explain the increase in fat oxidation
Because malonyl-CoA normally inhibits CPT1 causing reduced fatty acid oxidation
How is malonyl-CoA made?
actyl-CoA > malonyl-CoA > fatty acids
Acetyl-CoA carboxylase exists as 2 converts step 1
Fatty acid synthase converts step 2
What is the function of ACC1 and ACC2?
ACC2 = associated with mitochondria (where FA oxidation takes place)
Malonyl-CoA produced by ACC2 = mainly used to regulate FA oxidation (rather than FA synthesis)
