Sources and Sinks of amino acids
Required only during periods of growth and is generally not required by the adult
Essential amino acids
Pvt. Tim Hall:
Phenylalanine, valine, thryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine
Waste product of amino acid catabolism
Encephalopathy caused by a loss of funtion of the liver and buildup of ammonia, resulting in ammonia poisoning.
Amino acid metabolism outline
Pathway of dietary amino acid absorption
Amino acid transit via enterocytes
_____ pass through the liver and are used primarily as an alternative energy source by peripheral muscle (especially in fasting) or adipose tissue (in the fed state).
leucine, isoleucine, and valine (the branched nonpolar amino acids) pass through the liver and are used primarily as an alternative energy source by peripheral muscle (especially in fasting) or adipose tissue (in the fed state).
This is because the liver lacks an enzyme required for metabolism of branched chain amino acids.
Pancreatic response to dietary amino acids
The ability of glucagon to stimulate ____ is important to maintain blood glucose levels after ____.
The ability of glucagon to stimulate gluconeogenesis is important to maintain blood glucose levels after a high protein meal.
Regulation of muscle protein breakdown
In skeletal muscle, cortisol exerts its effects at the level of ____.
In skeletal muscle, cortisol exerts its effects at the level of transcription.
Akt/PKB in amino acid metabolism
Regulatory transcription factor that promotes the expression of E3’s that recognize and ubiquitinate skeletal muscle protein, leading to their degradation. (in addition to many other functions)
Muscle is thought to be broken down by ___ in the fasted state.
Muscle is thought to be broken down by the ubiquitin proteasome pathway AND autophagy in the fasted state.
Fate of absorbed amino acids
The glucose-alanine cycle
_____ are often the first step in amino acid metabolism.
Transamination reactions are often the first step in amino acid metabolism.
Reaction catalyzed by aminotransferase
All aminotransfer reactions share a common _____.
All aminotransfer reactions share a common mechanism AND cofactor (B6, pyridoxal phosphate).
High levels of pyruvate in muscle promotes. . .
. . . transfer of amino groups to pyruvate to form alanine.
The common amino group donor is ____.
The common amino group donor is glutamate.
Maple Syrup Urine Disease
The urine in these patients has the odor of maple syrup due to the presence of α-keto acids.
Caused by a partial or complete deficiency in the branched-chain α-keto acid dehydrogenase complex, which causes these amino acids and their ketoacids to accumulate in the blood. Their accumulation interferes with brain function and infants with this disease show symptoms within the first several days after birth. This disease is lethal within the first few weeks of life if left untreated.
Treatment of maple syrup urine disease
The disease is treated using a formula that contains just enough branched chain amino acids for normal growth, but not enough for toxic accumulation of the amino acids or their metabolites.
Branched-chain amino acid metabolism
Aspartate, glutamate, and glutamine metabolism in the liver
Only the ____ from aspartic acid is consumed by the urea cycle
Only the amino group from aspartic acid is consumed by the urea cycle
its carbon skeleton is recycled, via the TCA cycle by forming fumarate
Oxidative deamination of glutamate
Catabolism of amino acid carbon skeletons
Roles of the urea cycle
- To get rid of nitrogenous waste
- To supply arginine
The Urea Cycle
Link between urea and TCA cycles
The main form of urea cycle regulation is. . .
. . . substrate availability
Major activators of urea cycle
1. High protein diet
Arginine plays a special role in the urea cycle because it. . .
. . . accelerates flux through the urea cycle
The urea cycle produces ____ which enters the TCA cycle and generates ____ that can be transaminated to ____ for the urea cycle
The urea cycle produces fumarate which enters the TCA cycle and generates oxaloacetate that can be transaminated to aspartate for the urea cycle
Glutamine and glutamate transport between peripheral tissues and the liver
Glutamate synthetase in peripheral tissues uses energy from ATP hydrolysis to fix a free ammonia onto glutamate, forming glutamine.
That glutamine is then shuttled to the liver, where hepatic glutaminase hydrolyzes off the ammonia, targeting it for the urea cycle, regenerating glutamate.
Why does the glutamate/glutamine system work so well for transferring ammonia?
Because the amino group transferred in this cycle is not an α-amino group. Remember that transaminases act only on α-amino groups, not on side chains.
This separates the reaction from the rest of transaminase nitrogen metabolism.
The only oxidative deaminase
Glutamate dehydrogenase. This is the only one the body really needs, since all the other amino acids can feed into the glutamate pathway via transaminases.
___ and ___ aminotransferases are the most highly expressed in the liver.
Aspartate and alanine aminotransferases are the most highly expressed in the liver. This is because of the special role of aspartate in the urea cycle and the role of alanine in the alanine cycle.
In the urea cycle, the ammonia that goes into carbamoyl phosphate comes from ____. The aspartate amino group comes from ____.
In the urea cycle, the ammonia that goes into carbamoyl phosphate comes from glutamate dehydrogenase. The aspartate amino group comes from glutamate via aspartate aminotransferase.
Both are ultimately utilizing glutamate as their source for nitrogen.
High AST, low ALT
Not likely to be liver damage
High AST, High ALT
Highly suggestive of liver damage
The ____ carbon skeleton must be obtained from the diet.
The arginine/ornithine/citrulline carbon skeleton must be obtained from the diet.
Something which fills up a cycle and thus speeds it up.
Anaplerotic describes the role of ____ in the urea cycle.
Anaplerotic describes the role of arginine in the urea cycle.
___ is to the urea cycle as oxaloacetate is to the krebs cycle.
ornithine is to the urea cycle as oxaloacetate is to the krebs cycle.
____ is highly characteristic of hepatic encephalopathy.
asterixis is highly characteristic of hepatic encephalopathy.
Asterixis is when a patient has an involuntary tremor "flapping" in their hand.
What is the importance of insulin produced in response to gluconeogensis in a high protein meal?
It keeps skeletal muscle from being degraded in the presence of high levels of dietary amino acids, even when the meal contains no glucose whatsoever.
No ___ is produced by high protein meals.
No glycogen is produced by high protein meals.