Cholesterol and Protein Metabolism
What is cholesterol the precursor to?
bile salts and steroid hormones
What is the precursor to steroid synthesis?
What is a ketoacid?
what is left when the amino group is removed from an amino acid
Where is the amino group from a ketoacid normally transferred?
to another ketoacid
What area a-ketoacids used for?
ATP+H2O+CO2, glucose, ketones, and fatty acids
What do we get when we add NH3+ and pyruvate?
glutamate - NH3+=?
Pyruvate, a-ketoglutarate and oxaloacetate are?
What are the purely ketogenic amino acids?
leucine and lysine
Are carriers inducible?
yes, the body can make more or less of them
What is absorbed faster, BCAAs or smaller amino acids?
What is absorbed more, peptides or free AAs?
What % of absorption is peptide?
What % of absorption is free amino acid?
What happens to peptides once into the enterocyte?
broken down to free AAs for the blood
What is the function of the gamma-glutamyl cycle?
to get an amino acid into a cell
What happens in the gamma-glutamyl cycle?
glutamate breaks off glutathione and escorts amino acids into cells
What is glutathione?
What is the primary site for amino acid uptake following a meal?
What % of amino acid uptake takes place in the liver after a meal?
What amino acids is skeletal muscle able to oxidize?
leucine, isoleucine, valine, glutamate, aspartate, and asparagine
How much of protein is found in its free form in the free amino acid pool?
less than 2%, 200 grams
What is the ratio of intracellular to extracellular glutamate?
>50 to 1
What is anaplerosis?
adding to the pathway
What is cataplerosis?
taking from the pathway
What are the two products of an amino acid being broken down?
NH3 and a-keto acids
What enzyme is lacking in skeletal muscle?
glucose 6 phosphatase
What is the function of glucose 6 phosphatase?
to form glucose to be released into the blood
Because muscle is lacking glucose 6 phosphatase, how does it release glucose into the blood?
the cori cycle and the glucose-alanine cycle
What are the steps of the cori cycle?
muscle glycogen ->glucose 6P ->pyruvate->lactic acid ->to liver ->pyruvate->glucose -> to blood
What are the steps of the glucose-alanine cycle?
muscle glycogen->glucose 6P->pyruvate->alanine->to liver->pyruvate->glucose ->to blood
How does the glucose-alanine cycle maintain blood glucose?
What is the main source of nitrogen?
What are the steps of the glutamine-glutamate cycle?
muscle imports glutamate, muscle turns glutamate into glutamine, glutamine goes to cells needing nitrogen, glutamine turns back into glutamate, glutamate goes back to the muscle
How does muscle turn glutamate into glutamine?
glutamine synthetase adds nitrogen to glutamate, nitrogen is taken from amino acids
What cells need nitrogen?
gut and immune cells
How is glutamine turned back to glutamate?
glutaminase hydrolyzes glutamine
How are most amino acids released?
in proportion to their relative occurrence in muscle protein
What amino acids are not released in proportion to their relative occurrence in muscle protein?
leucine, isoleucine, valine (BCAAs), glutamate, aspartate, asparagine, glutamine, and alanine
What amino acids are released in amounts less than what is taken in?
BCAAs, glutamate, aspartate, and asparagine
What are the most abundantly released amino acids?
glutamine and alanine (50% and 30%)
When is there a large uptake of BCAA and glutamate?
Describe the uptake of BCAA and glutamate after eating:
large uptake: more than 90% of muscle amino acid uptake
Why doesn't the gut have a large uptake of BCAAs?
it lacks sensitivity
What happens to muscle release of glutamine after eating?
it more than doubles
What is a large source of ATP creation for muscle?
What inhibits pyruvate degradation during starvation?
BCAAs, allowing pyruvate(lactate or alanine) to leave for gluconeogenesis
What is the function of alanine aminotransferase in muscle?
to take the NH3 group from gluatamte and give it to nitrogen, forming alanine and a-ketoglutarate
What is low intensity exercise?
25% of VO2 max
What is the effect of low intensity exercise on skeletal muscle glutamate concentration?
What is the effect of low intensity exercise on skeletal muscle alanine concentration?
What is moderate intensity exercise?
50% of VO2 max or more
What is the effect of moderate intensity exercise on skeletal muscle glutamate concentration?
40% decrease during the first minute
What is the effect of moderate intensity exercise on skeletal muscle alanine concentration?
40% increase in first minute
What is the effect of moderate intensity exercise on skeletal muscle glutamine concentration?
What happens to glutamate plasma concentration during exercise?
What happens to alanine plasma concentration during exercise?
What happens to glutamine plasma concentration during exercise?
What happens to glutamate intake in the initial phase of moderately intense exercise?
increases 1-3 fold
What happens to glutamine and alanine intake in the initial phase of moderately intense exercise?
increases 2-9 fold
On the graphs, which graph represents glutamate?
the one with drops
On the graphs, which graph represents alanine?
the one with increases
What happens to ATP turnover during exercise?
it can increase 100 fold
What happens to TCA intermediates during exercise?
increase 4-10 fold
What is the main player in anaplerosis?
What is the substrate of TCA cycle?
What do we need to meet the ATP demands during exercise?
more TCA intermediates to combine with oxaloacetate, malate, succinate and fumarate all increase 5-6 fold
Why do we run fast glycolysis?
to create anaplerosis for the TCA
What is essential for exercising at high workloads?
What is responsible for the elevation of TCA cycle intermediates?
glycogen and alanine aminotransferase (ALT)
Can nitrogen be stored in the body?
Where is nitrogen sent?
What happens to excess amino acids?
they are degraded
How do we remove the amino groups from amino acids?
transamination, oxidative deamination
How is nitrogen excreted?
Why is nitrogen going to the liver?
ate too much protein, gluconeogenesis (exercise, starvation, not eating carbs)
Where does transamination happen?
liver and skeletal muscle
What do most amino acids transfer their amino group to?
glutamate and an a-keto acid
What enzyme transfers amine groups from amino acids to a-ketoglutarate?
What are the main ways nitrogen leaves the muscle?
glutamine and alanine
What enzyme is required to continually form glutamine and alanine?
Where do oxidative deamination, carbomoyl phosphatase and the urea cycle take place?
What is ALT?
Where is ALT found?
muscle and liver
What is the function of ALT in muscle?
change pyruvate+glutamate to alanine+a-ketoglutarate
What is the function of ALT in the liver?
change alanine+a-ketoglutarate to pyruvate+glutamate
What is GDH?
What is the function of GDH?
change glutamate+NAD+ to a-ketoglutarate+NH3 + NADH
What is AST?
What is the function of AST?
transfers amino groups from glutamate to oxaloacetate forming aspartate, glutamate+OAA to a-ketoglutarate + aspartate
What are the key liver enzymes?
ALT and AST
What is the function of the urea cycle?
the livers way of dealing with ammonia
What is the function of gluconeogenesis?
liver turns a-ketoacids into glucose
How does 86% of the nitrogen leave the body?
What is the function of carbamoyl phosphatase?
catalyzes CO2+NH3+2ATP to carbamoyl phosphate, the entry point of the urea cycle
Where is carbamoyl phosphatase found?
What three things can enter the urea cycle?
carbamoyl phosphate, aspartate, and H2O
What are the four intermediates of the urea cycle?
citrulline, argininosuccinate, aginine, and ornithine
What are the products of the urea cycle, starting with ornithine?
ornithine+carbamoyl phosphate = citrulline +aspartate= argininosuccitate-fumarate= arginine +H2O= urea
What is the structure of urea?
H2N-C=O-NH2, Ns bond to C
How many nitrogen molecules on urea?
Where do the two nitrogens on urea come from?
one from aspartate, one from free NH3
What is the precursor for NH3 and aspartate?
What conversion gives us free NH3?
glutamate to alpha KG