Flashcards in Amino Acid Metabolism Deck (87):
How do amino acids enter the TCA cycle?
Via acetyl CoA, a ketolutarate, succinyl CoA, fumarate, OAA and pyruvate
What are cofactors for amino acid metabolism?
PLP (pyridoxal phosphate), tetrahydrofolate (FH4), tetrahydrobiopterin (BH4)
In what location can all of the enzymes for amino acid synthesis and breakdown be found?
In the liver
What are the two classifications of amino acid breakdown?
Glucogenic and ketogenic
What amino acids undergo ketogenic breakdown only?
Leucine and Lysine
What amino acids can undergo ketogenic breakdown?
leucine, lysine, isoleucine, threonine, phenylalanine, tyrosine, and tryptophan
What amino acids undergo glucogenic breakdown?
All the amino acids except leucine and lysine.
Amino acid carbons are converted to intermediates of ____.
Glycolytic pathways, TCA cycle, and lipid metabolism
The first step of amino acid metabolism
A transfer of the alpha-amino group by transamination to alpha-ketoglutarate or oxaloacetate, or by providing glutamine and asparagine (sources for nitrogen of urea cycle)
True or false: All amino acids undergo transamination
FALSE: LYSINE CANNOT UNDERGO TRANSAMINATION
What amino acids end up as acetyl CoA?
KWIT (threonine, tryptophan, isoleucine, lysine)
Where does leucine enter the ketogenic pathway?
Where does tyrosine enter the ketogenic pathway?
As a ketone body
Where does glycine enter the ketogenic pathway?
Where does valine enter the ketogenic pathway?
Where does phenylalanine enter the ketogenic pathway?
as a ketone body
What enzyme or cofactor is required for the transamination of aspartate into oxaloacetate?
PLP (pyridoxal phosphate)
Some leukemic cells have low _____ activity and require ____.
low asparagine synthetase activity
What is used to treat acute lymphoblastic leukemia?
Asparaginase (it reduces serum asparagine, and leukemic cells have low asparagine synthetase activity)
What amino acids enter the pathway as pyruvate?
CAST (Cysteine, alanine, and serine directly, threonine indirectly)
How does cysteine enter metabolism?
Converts to pyruvate or taurine (bile salts)
A lack of this protein may cause kidney stones
(Called oxaluria type I)
Oxaluria type I results from a lack of ___.
Glycine can be broken down in a few ways. What is the most direct?
What is the other pathway?
Glycine cleavage enzyme uses NAD+ and some FH4 molecule thing I don't understand to cleave glycine into carbon dioxide and ammonium. NADH and N5,N10-Ch2-FH4 are also produced. (Doesn't require TPP)
Glycine to glyoxylate to either oxalate or alpha-hydroxy-beta-ketoadipate (when combined with alpha-keto-glutarate) which is then degraded to carbon dioxide and water
What do EDTA, citrate, and oxalate have in common?
They all bind calcium
3-phosphoglycerate is a precursor for __.
Serine, cysteine, and glycine
Serine, cysteine, and glycine are formed from ___.
Serine is a precursor for ___.
Glycine and cysteine
Cysteine and glycine can be made from ___.
Known synthesis of cysteine from serine
uses serine and homocysteine, cystathionine intermediate, creates alpha-ketobutyrate and cysteine
Homocystinuria is a result of ___.
Defects in cystathionine beta-synthase
Defects in cystathionine beta-synthase result in ___.
What is homocystinuria?
High homocysteine levels increase risk for coronary heart disease and arteriosclerosis, dislocation of eye lens. The amino acid damages cells lining blood vessels and raises oxidative stress. Treat with vitamin B6 (pyridoxal phosphate), some mutations respond to increased pyridoxal phosphate concentrations.
Where does homocysteine come from?
The catabolism of valine, isoleucine, and leucine occurs in ____.
skeletal muscle (not in the liver)
What enzyme is responsible for the first step of the metabolism of valine, isoleucine, and leucine?
BCAA transaminase, which is compartmentalized for efficiency and there is a much higher concentration in skeletal muscle than the liver. Branched chain amino acid transaminase.
What are things to know about BCAA transaminase?
It has higher concentrations in skeletal muscle than the liver. One mol of a branched chain amino acid yields 101 moles of ATP. Alanine carries amino groups back safely for disposal by liver as urea.
BCAA transaminase converts valine to a branched chain keto acid. BCKA dehydrogenase converts the BCKA to a branched chain acyl CoA. This is converted to propionyl CoA.
BCAA transaminase converts isoleucine to a branched chain keto acid. BCKA dehydrogenase converts the BCKA to a branched chain acyl CoA. This is converted to propionyl CoA.
BCAA transaminase converts leucine to a branched chain keto acid. BCKA dehydrogenase converts the BCKA to a branched chain acyl CoA. This is converted to acetoacetyl CoA.
Elevated levels of alpha-ketoacids of the branched chain amino acids is associated with what problems and disease?
Branched chain keto acid dehydrogenase. The disease is called maple syrup urine disease.
What vitamin might be used to treat newborns with elevated levels of branched chain keto acids?
Thiamine/vitamin B1. BCKA dehydrogenase requires Thiamine.
What is MSUD?
Maple Syrup Urine Disease is caused by a genetic defect in branched chain keto acid dehydrogenase. It is autosomal recessive. It is more common in the Pennsylvania Amish community. The symptoms are vomiting, lethargy, and severe brain damage. The symptoms start in early infancy and death often occurs before first year because leucine crosses the blood-brain barrier
It will show increased branched chain amino acids and alpha-ketoacids in urine and plasma. It will show a urine positive test with 2,4-dinitrophenylhydrazine (which reacts with ketones and aldehydes).
Propionyl CoA metabolism
Carboxylase converts propionyl CoA, bicarbonate, and ATP to methylmalonyl CoA using biotin. Methylmalonyl CoA mutase (and cofactor B12) converts methylmalonyl CoA to succinyl CoA, which enters the TCA cycle.
Elevation of ___ indicates vitamin B12 deficiency.
Methylmalonyl will build up if there is a deficiency of ____.
What are the essential amino acids?
MILK FTW HV (Methionine, isoleucine, leucine, lysine, phenylalanine, threonine, tryptophan, histidine, valine)
Why is Phe required?
What are the three branched chain amino acids?
Valine, isoleucine, and leucine. The notes say that Threonine is also metabolized like branch chained amino acids though
Why is tryptophan essential?
The complex heterocyclic side chain can not be synthesized by humans
Why is methionine essential?
It provides sulfur for cysteine and is a methyl donor in metabolism (SAM); homocysteine is recycled
Why is histidine esential?
Humans can not synthesize its complex heterocyclic side chain
Coverted to tyrosine using phenylalanine hydroxylase, then tyrosine aminotransferase converts tyrosine to p-hydroxyphenylpyruvate (using PLP as a cofactor), then hydroxyphenylpyruvate dioxidase converts that to homogentisate. Homogentisate uses homogentisate oxidase and then fumarylacetoacetate hydrolase to yield acetoacetate and fumarate.
What is required for conversion of phenylalanine to tyrosine?
Tetrahydrobiopterin or vitamin BH4 for hydroxylation is needed (as well as phenylalanine hydroxylase).
A defect in phenylalanine hydroxylase results in ___.
A defect in tyrosine aminotransferase results in ____.
A defect in hydroxyphenyl pyruvate dioxidase results in ____.
A defect in homogentisate oxidase results in ___.
A defect in fumarylacetoacetate hydrolase results in ___.
PKU is caused by a defect in ___.
phenylalanine hydroxylase (more rarely dihydropteridine)
A defect in dihydropteridine reductase can cause ___.
PKU, because the enzyme is needed to regenerate BH4 (PKU is most commonly caused by phenylalanine hydroxylase)
How do you diagnose hyperphenylalaninemia?
Increased phenylpyruvate (in blood/urine),
diagnosed via mass spec
Untreated infants with PKU develop these symptoms
Irreversible mental retardation (IQ
How is PKU treated?
Diet of Lofenalac, which is a semisynthetic supplement that reduces phenylalanine intake while maintaining normal intake of all other dietary nutrients
The diet is critical in first decade of life, but even adults will develop neurological sequelae if Phenylalanine rises.
Kuvan: synthetic version of tetrahydrobiopterin (some patients respond)
Persons with PKU also require supplements of ___.
Tyrosine (They will have lighter skin coloring as well if they are not receiving tyrosine)
Oxalate is in the metabolic pathway of ____.
Glycine (Buildup of oxalate is due to a deficiency in transaminase that converts glyoxylate to glycine and results in increased oxalate)
What is the defective enzyme in alcaptonuria?
A defect in homogentisate oxidase causes what disease?
Homogentisate accumulates and autooxidizeds, resulting in dark pigment that discolors urine and stains diapers. It is fairly benign. Chronic accumulation in cartilage may cause arthritic joint pain later in life (ochronotic arthritis)
Type III tyrosinemia is due to a defect in ___.
What molecule is associated with this enzyme?
hydroxyphenyl pyruvate dioxygenase,
NTBC, an inhibitor of HPP dioxygenase, affects this enzyme
What are the enzymes and products involved in type I tyrosinemia?
How is it treated?
The defective enzyme is fumarylacetoacetate hydrolase. Succinylacetone is produced, which is toxic to the liver
It is treated with NTBC, which inhibits hydroxyphenyl pyruvate dioxidase/dioxygenase.
Type II tyrosinemia
Genetic deficiency in tyrosine aminotransferase that results in eye and skin lesions and neurological problems. It is treated with a low phenylalanine and low tyrosine diet.
What is neonatal tyrosinemia?
HPP dioxygenase activity is low before birth and rises until near birth. HPP dioxygenase is vitamin C dependent. Premature infants should have low protein diet supplemented with 100 mg/day ascorbic acid
Products of tryptophan degradation:
alanine, acetyl CoA, carbon dioxide, nicotinamide moeity of NAD and NADP, xanthurenic acids and other urinary metabolites
Kynurenic hydroxylase requires PLP
What amino acids produce propionyl-CoA?
VTIM (Threonine, methionine, isoleucine, and valine)
What are the products of leucine degradation?
HMG CoA, then acetoacetate and acetyl-CoA
What are the products of Lysine degradation?
Acetyl-CoA via complex pathway
What are the products of tryptophan degradation?
Acetyl-CoA and alanine
What are the products of proline and histidine degradation?
What are the products of alanine degradation?
pyruvate by transamination
What are the products of arginine degradation?
Urea and glutamate
What are the products of aspartate and asparagine degradation?
Oxaloacetate by transamination
What amino acids produce glutamate?
proline, histidine, and arginine (and glutamine)
What amino acids produce acetyl-CoA?
Leucine, Lysine, Tryptophan
What amino acids produce oxaloacetate?
Aspartate and asparagine
What amino acids produce pyruvate?
alanine, tryptophan (makes alanine), Serine, cysteine, Glycine (makes alanine), and Threonine (Makes glycine)