Urea Cycle Flashcards
________ is a chemical reaction between two molecules. One is an amino acid, which contains an amine (NH2) group. The other is a keto acid, which contains a keto (=O) group.
Transamination
______ is the removal of an amine group from a molecule. Enzymes that catalyse this reaction are called deaminases
deamination
____ is deaminated in the kidneys, but the majority of things are deaminated in the ______
glutamate, liver
over 90% of nitrogen excretion is in the form of ______
urea
________ is the degradation product of purine bases
uric acid
list four purine bases
adenine, guanine, hypoxanthine and xanthine
______ is released from glutamate, especially by the _____
ammonia, kidneys
NH3
ammonia
____ is a very important ion for pH control and buffering of urine
ammoium ions (NH4+)
transamination rxns are catalyzed by transaminsases, aka ______
aminotransferases
_____ is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid.
transaminases/aminotransferases
what is the major cofactor for transamination rxns?
pyridoxal phosphate
what are the 3 transamination pairs?
asparate & oxaloacetate,
glutamate & alpha-ketoglutarate,
alanine & pyruvate
pyridoxal phosphate (PLP) is derived from _______
Pyridoxine (vit B6)
all AA except what 3 can undergo transamination?
lysine, threonine, proline
for almost all reactions the ____________ pair serves as one of the alpha-keto AA pairs
alpha-keotglutarate - glutamate
is transamination reversible?
yes
____ is the transaminase that present in the cytoplasm of liver cells
alanin transaminase (ALT) aka as glutamic pyruvic transaminase - GPT
____ is the transaminase that present in liver, heart, and skeletal muscle
aspartate transaminase (AST) aka as glutamic oxalacetic transaminase-GOT
damage to specific organs will result in an increase of serum levels of what?
ALT and AST (corresponding to the organ)
describe the first rxn of the urea cycle
ammonium ions (NH4+) are rapidly converted to carbomoyl phosphate, this occurs in the mitochondria
what are the allosteric inhibitor of glutamate dehydrogenase (GDH) for oxidative deamination
high ATP, GTP, and NADH
what is glutamate dehydrogenase?
it is an enzyme that catalyzes oxidate deamination between glutamate and alpha-ketoglutarate, which releases ammonium
which amino acid is known as the “gate-way” amino acid and why?
glutamate, it always serves as one of the amino acids in transaminations
where does oxidative deaminatio by L-amino acid oxidase mainly occur?
in the liver and kidneys
what cofactor is needed for oxidative deaminatio by L-amino acid oxidase?
FMN (flavin mononucleotide)
ammonium ions produced by non-oxidative deamination in non-hepatic tissues are transported to the liver in the form of what 3 possible things?
glutamate, glutamine, or alanine
name the non-oxidative dehydration enzymes
Serine dehydratase,
Threonine dehydratase,
D-cysteine desulfhydrase
name the non-oxidative hydrolytic enzymes
Glutaminase & Asparaginase
Free ammonium ions in nonhepatic tissue are primarily detoxified by what enzyme?
glutamine synthetase
glutamine synthetase make glutamine which then carries free ammonium ions to the liver for final conversion to what?
urea
what enzyme is especially important in the kidney whose main function is the production of ammonia for acid-base regulation
glutaminase
______ is a major amino acid of circulation; its role is to ferry ammonia to and from various tissues
glutamine
In kidney, glutamine is hydrolyzed by ______ releasing the ammonia to the urine
glutaminase
when does the liver divert ammonia to glutamine, then the kidney converts to a-ketoglutarate yields 2 NH4+ which reduces the H+ concentration.
under acidotic conditions
(T/F) Humans are totally dependent on other organisms for converting atmospheric nitrogen into forms available to the body
true
what is the primary source of nitrogen metabolized by the body?
dietary proteins
is ATP required for the urea cycle?
yes
where does the formation of carbamoyl phosphate occur?
the mitochondria
how many nitrogens does aspartate provide?
one
____ is released from arginine in a reaction catalyzed by _____
urea, arginase
In the liver, the ammonia produced from what 3 things is converted to urea through urea cycle?
Glutamate, from AMP, or by direct deamination
Carbon dioxide and ammonium ion react with two molecules of ATP to form _____
carbamoyl phosphate
what 3 things react to form carbomoyl phosphate?
Carbon dioxide and ammonium ion react with two molecules of ATP
____ or _____ can serve as the cofactor for glutamate dehydrogenase (GDH)
NAD+ or NADP+
CPS1
Carbamoyl phosphate synthetase
in the 2nd rxn of the urea cycle, Carbamoyl phosphate reacts with ______ to form ______, which moves out of the mitochondrion into the cytoplasm.
ornithine, citrulline
what are 2 major promoters of the urea cycle?
NH4+ and glutamate
the ctivation of carbamoyl phosphate synthetase I (CPSI) requires what precursors?
glutamate and acetyl CoA react with arginine to for N-acetyl glutamate
describe the second rxn in the urea cycle
carbamoyl phosphate and ornithine are catalyzed by ornithine transcarbamoylase to form citrulline
describe the 3rd rxn of the urea cycle
citrulline and aspartic acid are catalyzed by arginosuccinate synthetase to form arginosuccinate
where do the rxns 3-5 of the urea cycle take place?
in the cytoplasm
describe the 4th rxn of the urea cycle
arginosuccinate is catalyzed by arginosuccinate lyase to form arginine and fumurate
describe the 5th and last rxn of the urea cycle
arginine is gatalyzed by arginase to form ornithine and urea
Carbamoyl phosphate synthetase (CPS) is dependent on ________ for activity
N-acetylglutamate
Synthesis of N-acetylglutamate is catalyzed by _________
N-acetylglutamate synthetase
_____ is an allosteric activator of N-acetylglutamate synthetase
Arginine
Defects in urea cycle result in what?
accumulation of ammonia in the blood
All of the deficiencies of components needed for the urea cycle may present with _______
hyperammonemia
define hyperammonemia
a metabolic disturbance characterised by an excess of ammonia in the blood
brain damage, coma, and death due to lack of ATP, neural defects, and the depletion of glutamate stores needed to make GABA (the neurotransmitter) are all results of what?
ammonia intoxification
(T/F) glutumate can readily cross the BBB
False, it cannot cross the BBB
what are the 3 possible Tx’s for defects in the urea cycle enzymes?
limit protein intake, remove excess ammonia, and replace missing intermediates from the cycle
what two things can be used to remove excess ammonia from the blood stream?
sodium benzoate and sodium phenylacetate to bind up glycine and glutamine
To Tx defects in the urea cycle enzymes you can replace the missing intermediate with ______ or_______
arginine or citrulline
in the kidneys and more acidic condition _____ breakdown of glutamine and a less acidic condition ____ the breakdown
increase, decrease
Kidneys and intestines jointly produce _______
arginine
Massive resection of the small intestine can cause patients to become ______ deficient
arginine
intestinal CPS1 and OTC form ______ which is exported into the blood and taken up by the kidneys to for arginine
citrulline
____________ is the major process for removing nitrogen from amino acids
transaminase rxn
deamination or serine, glutamate dehydrogenase reactions, bacteria in the instestinallumen, and glutaminase reactions are all sources of_____
ammonium (NH4+)
what are the 4 main products of nitrogen metabolism?
urea, ammonia, creatinine, and uric aicd
______ is the mechanism for continuously supplying tissues that use glucose as primary energy source during fasting, exercise etc.
the alanine cycle
in the alanine cycle the generation of amino nitrogen requires how many ATP’s for the disposal as urea?
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