Metabolism 10: Amino Acid Metabolism Flashcards
What is the normal body concentrations of free amino acids?
<1mM plasma
Where do free amino acids come from?
degradation of ingested protein
biosynthesis of some amino acids
degradation of endogenous proteins
What are free amino acids used for?
resynthesis of endogenous protein
precursor for synthesis of other biomolecules
energy production
What are nutritionally essential amino acids?
Amino acids that can't be synthesized in the body and thus must be obtained in the diet ARginine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine
What are the 2 primary pathways for protein degradation?
ATP dependent ubiquitin proteosome system
Lysosomal pathway
What kind of proteins tend to be degraded/resynthesized faster?
REgulatory proteins
How much of the total body protein do adults degrade and resynthesize every day?
2-3%
What happens to excess amino acids?
They are degraded, not stored. Even on a high protein diet there is nonet accumulation of protein
What is the obligatory/require amino acid degradation?
Degradation that occurs even if no protein is supplied in diet
It is about at least 55g of protein every day. This must be replaced by dietary protein
What happens when daily protein intake is less than 55g?
Loss of body protein
What happens when daily protein intake is greater than 55g?
excess amino acids are degraded, not stored
During amino acid catabolism what does the nitrogen in the amino group lead to and what does the carbon skeleton lead to?
Nitrogen: incorporated into urea and excreted
Carbon Skeleton: converted to compounds for energy production of glycogen/fat storage
What is nitrogen balance?
Nitrogen Balance = Nitrogen Ingested (protein) - Nitrogen excreted (Urea)
What are some examples of physiological states in whcih we have positive nitrogen balance?
Growth in children
Pregnancy
bodybuilding
Protein synthesis occurs at slightly higher rate tha protein degradation -> nitrogen accumulates
What are some examples of physiological states in which we have negative nitrogen balance?
Starvation, protein malnutrition, trauma, infection, cancer, burn injury, sepsis, surgery
Rate of protein synthesis is less than rate of protein degradation -> muscle mass decreases
Where does urea form and where is it excreted?
Synthesized in the liver and excreted in the kidney
Show the fate of the nitrogen of the amino group of amino acids
NH2 from amino acids -> glutamate -> Ammonia/Aspartate -> UREA
What is transamination?
A step in the degradation of most amino acids that transfers the amino group to a-ketoglutarate to form glutamate
What enzyme catalyzes transamination?
Aminotransferase (Transaminases): different ones that act on specific amino acids. All use a-ketoglutarate as amino group acceptor to form glutamate
What cofactor is required for transaminases?
pyridoxal phosphate (Derivative of Vitamin B6)
What are the 2 transaminases important for clinical diagnosis?
Alanine Transaminase (ALT) Aspartate Transaminase (AST)
Usually low in serum levels but increase in times of damage and cell necrosis causing release of cytosolic enzymes
How is aspartate formed during urea biosynthesis?
From glutamate using aspartate transaminase to form aspartate and a-ketoglutarate
How is ammonia formed during urea biosyntehsis?
From glutamate using glutamate dehydrogenase and NADP+ to form Ammonia and a-ketoglutarate and NADPH
Show the sequence of urea synthesis from ammonia and aspartate
Ammonia + Aspartate -> Carboyl phosphate -> Citrulline -> Argininosuccinate -> Arginine -> urea
What enzyme catalyzes the formation of carbamoyl phosphate?
Carbamoyl Phosphate Synthetase I
Requires N-acetylglutamate
What enzyme catalyzes the formation of citrulline ?
Ornithine transcarbamylase
What enzyme catalyzes the formation of argininosuccinate?
Argininosuccinate Synthetase
What enzyme catalyzes the formation of arginine from argininosuccinate
Argininosuccinate Lyase
What enzyme catalyzes the formation of urea and ornithine from arginine?
Arginase
Which steps of urea biosynthesis occurs in the mitochondria?
Synthesis of carbamoyl phosphate and citrulline. All others take place in cytosol
Which intermediate compound of urea biosynthesis leaves the mitochondria?
Citrulline
Which intermediate compound of urea biosynthesis enters the mitochondria?
Ornithine
How does N-acetylglutamate regulate urea biosynthesis?
It activates the enzyme making carbamoyl phosphate (Carbamoyl Phosphate Synthetase I) to stimulate urea production
What causes an increase in the levels of N-acetylglutamate?
Increased levels of glutamate (due to transamination of amino acids from dietary protein)
What can lead to increased levels of urea cycle enzymes?
Long term exposure to high protein diet or a high rate of protein degradation
How is nitrogen from other metabolic tissue transferred to liver for conversion to urea?
Carried by alanine and glutamine to liver. Thus they are present in blood at higher concentrations than other amino acids
What is BUN and its normal value?
Plasma urea concentration. Normal: 7-30 mg/dl
What is the function of urea biosynthesis?
Detoxification of ammonia
What can happen when ammonia levels are too high (hyperammonemia)?
Predisposition to coma.
Hepatic coma due to decreased ability of liver to remove ammonia via urea production
What can cause acquired hyperammonemia?
Portal-Systemic Shunting: diversion of blood flow around liver in response to cirrhosis
What can cause portal-systemic encephalopathy?
when ammonia produced by intestinal bacteria is absorbed but not converted to urea in the liver causing hyperammonemia
What is a genetic cause of hyperammonemia?
Deficiency of a urea cycle enzyme
What are glucogenic amino acids?
amino acids whose carbon skeletons are used to generate TCA intermediates or pyruvate for gluconeogenesis
What are ketogenic amino acids?
amino acids whose carbon skeletons are used to generate acetyl-CoA, acetoacetyl CoA, or acetoacetate
Which amino acids are ketogenic?
leucine, lysine
Which amino acids are boht ketogenic and glucogenic?
Isoleucine Phenylalanine Threonine Tryptophan Tyrosine
What happens with regards to protein and amino acid metabolism during a fed state?
Get net protein synthesis using 1/3 of the newly absorbed amino acids (remaining 2/3 degraded)
How does insulin during the fed state affect amino acid metabolism?
It inhibits protein degradation and stimulates protein syntehsis
What happens with regards to protein and amino acid metabolism during a fasted state?
Get net protein degradation due to decreased amino acid and insulin levels. Released amino acids are used by liver for gluconeogenesis
