Chapter 17: Amino Acid Metabolism Flashcards
Amino acids released from proteins go through deamination or transamination produce C skeletons that the liver can convert to what products?
glucose (glucogenic amino acids)
acetyl CoA,
ketone bodies (ketogenic)
Amino groups released by deamination form which ion?
ammonium ion (NH4+)
How do most tissues add excess amino acids to blood?
*add excess nitrogen to the blood as glutamine by attaching ammonia to the y-carboxyl group of glutamate
How is lactulose used to treat hyperammonemia?
lactulose is metabolized to lactic acid in GI by bacteria
lactic acid in turn converts ammonia (NH3) to ammonium (NH4+) interfering with absorption and treating hyperammonemia
Be able to draw out a diagram for amino group removal for elimination as urea and ammonia.
Refer to diagram
What is the enzyme that capture nitrogen and in turn converts glutamate to glutamine to be released out into the circulation?
glutamine synthetase
What is the purpose of glutaminase in the kidney?
an enzyme that deaminates glutamine arriving in the blood and eliminates the amino group as ammonium ion in the urine.
What is another name for aminotransferases?
transaminases
What is the function of transaminases? Compare to deaminases?
unlike deaminases, do not release the amino groups
This class of enzymes transfers the amino group from one carbon skeleton (an amino acid) to another (usually a-ketoglutarate, a citric acid cycle intermediate)
What vitamin mediates the transfer of an amino group from one carbon skeleton (an amino acid) to another (usually a-ketoglutarate)
Pyridoxal P Vitamin B6
How are aminotransferases named? ALT stands for? AST stands for?
according to the amino acid donating the amino group to a-ketoglutarate.
ALT alanine aminotransferase (formerly GPT)
AST aspartate aminotransferase, (formerly GOT)
What organs are the aminotransferases usually found?
liver and muscle
The reactions catalyzed by aminotransferases are reversible or irreversible?
reversible and play several roles in metabolism
A portion of the glutamate formed in the muscle may be aminated by glutamine synthetase (as in other tissue or the amino group can be transferred to what metabolic product to make alanine?
pyruvate
What is the purpose of glutamate dehydrogenase?
enzyme found in many tissues where it catalyzes the reversible oxidative deamination of the amino acid gluatamate
How many nitrogens does urea contain?
2 nitrogens
N-acetylglutamate is only produced in what conditions?
when amino acids are present
Draw out the urea cycle.
Refer to diagram
Carbamoyl phosphate synthetase and ornithine transcarbamoylase are enzymes found where in the cell?
mitochondrial enzymes
The product urea is formed in the mitochondria or the cytoplasm of the liver?
the cytoplasm
Compare and contrast ammonia levels in carbamoyl phosphate synthetase deficiency and ornithine transcarbamoylase deficiency. (Ammonia levels, glutamine levels, BUN, orotic acid, inheritance pattern, brain abnormalities, symptoms.
Refer to chart
How can genetic deficiencies of urea synthesis be treated?
with a low protein diet and administration of sodium benzoate or phenylpyruvate to provide an alternative route for capturing and excreting excess nitrogen
Be able to create a diagram on genetic deficiencies of amino acid metabolism associated disorders and symptomology.
Another name for phenylketonuria?
phenylalanine hydroxylase deficiency
What is something people may add to a meal/drink that is strictly avoided in phenylketonurics?
aspartame (N-aspartylphenylalanine methyl ester) which is an artificial sweetener
Symptoms of PKU? What may their diet be low in as a treatment?
- intellectual disability
- musty odor
- microcephaly
- pale skin and white blonde hair (hypopigmentation)
low levels of phenylalanine (restricted) still needed because it is essential amino acid
The neurotoxic effects of PKU occur because of a high level of what in the blood?
high levels of phenylalanine and not the phenylketones from which the name is derived
What is treatment for PKU?
lifelong semi synthetic diet with restricted amounts of phenylalanine (small quantities are necessary because it is an essential amino acid)
Is PKU an example of allelic heterogeneity? Explain
yes because there are >100 known mutations in the gene for phenylalanine hydroxylase causing PKU
What is albinism?
group of conditions in which the normal conversion of tyrosine to melanin is altered. Most severe form is a deficiency of tyrosinase
Another name for homogentisate oxidase deficiency?
alkaptonuria
Explain the cause for dark urine in homogentisate oxidase deficiency.
accumulation of homogentisic acid in the blood causes it excretion in urine, after which it gradually darkens upon exposure to air
Ochronosis?
bluish-black discoloration of certain tissues, such as the ear cartilage and the ocular tissue
Why can ochronosis be seen in alkaptonuria?
Because the homogentisic acid in the blood accumulates in cartilage and may be seen in the sclera of the eye, in ear cartilage and patients develop arthritis in adulthood
Another name for Maple Syrup Urine disease.
Branched-chain ketoacid dehydrogenase Deficiency
How is branched chain ketoacid dehydrogenase an enzyme similar to a-ketoglutarate dehydrogenase?
needs all 5 cofactors/coenzymes:
thiamine, lipoic acid, CoA, FAD, NAD+
What does branched chain ketoacid dehydrogenase metabolize?
branched chain ketoacids produced from their cognate amino acids, valine, leucine, and isoleucine
Explain the progression of MSUD.
In the first few days of life, infants are normal, after which they become progressively lethargic, lose weight, and have alternating episodes of hypertonia and hypotonia and urine develops charcteristic odor of maple syrup
What are the amino acids metabolized through the propionic acid pathway?
valine
methionine
isoleucine
threonine
Deficiency in propionyl-CoA carboxylase and methylmalonyl CoA mutase results in what condition?
neonatal ketoacidosis from failure to metabolize ketoacids produced from the 4 amino acids: valine, methionine, isoleucine, and threonine
Propionyl CoA carboxylase deficiency involves an accumulation of what products?
propionic acid, methyl citrate, and hydroxypropionic acid
Methylmalonyl CoA mutase deficiency will lead to an accumulation of which products?
accumulation of methylmalonic acid
How do you treat propionyl CoA carboxylase deficiency?
a diet low in protein or a semisynthetic diet with low amounts of valine, methionine, isoleucine, and threonine
How do you treat methylmalonyl CoA mutase deficiency?
a diet low in protein or a semisynthetic diet with low amounts of valine, methionine, isoleucine, and threonine
What is the difference between homocysteine and homocystine?
homocystine is a disulfide dimer of homocysteine
Treatment for homocystinemia/homocystinuria?
treating the symptoms and a diet low in methionine
What is the major enzyme deficiency producing homocystinemia?
that of cystathionine synthase deficiency
Difference between subluxation of the lens in Maarfans vs homocystinemia?
In Marfaan subluxation of the lens is upward and outward;
In cystathionine syndrome subluxation of the lens is downward and inward
If left untreated those with cystathionine synthase deficiency usually succumb to what?
MI, stroke, or pulmonary embolism
When a biochemical reaction requires a methyl group (methylation) what is usually the methyl donor?
SAM S-adenosylmethionine is generally the methyl donor
If 1 carbon unit in another oxidation state is required (methylelene, methenyl, formyl) what is required?
THF tetrahydrofolate typically serves as the donor
Tetrahydrobiopterin (BH4) is a coenzyme for which enzymes? How is it regenerated?
tyrosine hydroxylase,
phenylalanine hydroxylase, and
tryptophan hydroxylase (serotonin synthesis)
and is regenerated by the dihydropteridine reductase
Parkinson’s disease is caused by loss of dopaminergic neurons in what part of the brain?
substantia nigra
What are important pathways requiring SAM?
include synthesis of epinephrine and of the 7 methylguanine cap on eukaryotic mRNA
Homocysteine methyl transferase requires what coenzymes/vitamins to convert homocysteine to methionine?
B12
N5-methyl THF
What are important pathways requiring THF?
synthesis of all purines and thymidine which are used for DNA and RNA synthesis during cell growth and division
How is additional folate stored in the body?
in the highly reduced N5-methyl-THF form
What is the only enzyme that uses N5 methyl THF? What enzyme does the vitamin require?
homocysteine methyltransferase which requires B12
