amino acid metabolism Flashcards
what protein stores amino acids?
there is none
protein turnover is about ___g / day
300-400
what are the 2 major protein degradation paths?
1) ubiquitin-proteasome path
2) chem signals
the hydrolytic cleavage of proteins by proteases
proteolysis
proteolysis occurs in ___ and ___
stomach; small intestine
purpose of chewing?
liquification, neural effects (histamine), surface area
gastric juice contains:
HCl (100mmol/L), pepsin, gastrin
pH alters ___ and ___ bonds
disulfide; hydrogen
pathway of protein digestion?
mouth–>stomach–>small intestine–>endothelial cells–>portal vein–>liver/peripheral tissues
inactive form of proteases are called:
zymogens
purpose of K/H pump in membrane of specialized stomach cells?
H+ go into stomach, K+ go out to gen. acidic enviro and release heat
wat does GERD stand for?
gastroesophageal reflux disease
example of proton pump inhibitor med?
prevacid
example of histamine H2 receptor blocker?
zantac
zymogens are activated by ___
proteolysis
why are proteolytic enzymes stored as zymogens?
so don’t break down proteins in cells where they are made/stored
2 steps of zymogen activation?
1) autocleavage
2) autocleaved activated enzymes activate the other zymogens
preferentially cleaves peptide bonds between hydrophobic and aromatic a.a.
pepsin
less specific proteolytic enzymes that cleave at ends of proteins are called:
exopeptidases (carboxy, amino)
preferentially cleaves peptide bonds after aromatic a.a.
chymotrypsin
cleaves peptide bonds following Arg or Lys
trypsin
cuts after a.a. w/ smaller hydrophobic side chains
elastase
why are there so many diff proteolytic enzymes?
enable diff substrate specificities to allow proteins cut into small bits rapidly
in transamination, amino acids are all funneled into ____
L-glutamate
glutamate–>alpha ketoglutarate called?
oxidative deamination (remove NH4)
urea only produced in ___
liver
transamination requires vit. ____
B6
transamination reaction doesn’t happen for _____
Lysine and Threonine
transamination has a Keq that is approximately ___
1 (reversible rxn)
__ of aminotransferases are used as a diagnostic tool
isozymes
3 pairings we need to know?
alpha ketoglutarate/glutamate; pyruvate/alanine; aspartate/oxaloacetate
what is the fate of glutamate in liver?
transport to mito and undergo oxidative deamination to release ammonia
oxidative deamination of glutamate by ____
glutamate dehydrogenase (remove amino group from Glu)
NH3 is ___, NH4 is ___
ammonia; ammonium (odourless, more common in body)
glutamate dehydrogenase is activated by ___, inhibited by ___
ADP, GTP
coenzymes of glutamate dehydrogenase?
NAD or NADP
NH4 reacts with glutamate to form ___, by enzyme called ____; this happens in tissue other than _____
glutamine; glutamine synthetase; muscle/liver
glutaminase is found in ___ to release free ammonia to convert to urea
mitochondria
glutamate forms ____ in muscle by transferring amino group to ___
alanine; pyruvate (gluconeogenesis to form gluc)
urea produced is __ into blood, ___ by kidney, ___ in urine
secreted; filtered; excreted
urea cycle occurs in ___ thru series of rxns in __ and __ of cell
liver; cytosol; mito
precursors of urea
NH4, CO2, aspartate
very good disinfectant/cleaner, found in old pee
ammonia
uncatalyzed elimination of urea is ____, urease catalyzed hydrolysis is ____
slow; fast
rate limiting step with this enzyme in urea synthesis
carbamoyl phosphate synthetase 1
CPS1 needs ___ as allosteric activator and obligatory (ne___ ATP
N-acetylglutamate ; 2
N-acetylglutamate synth from _____ by synthase stimulated by ___
acetyl coA, glutamate; arginine
second ammonium group in urea cycle from ___
aspartate
carbamoyl phosphate and ____ results in citrulline
ornithine
why are cytosolic rxns in urea cycle clustered?
rapid rxns, intermediates remain in complex, [ ] intermediates high, no side rxns
enzyme that uses water to turn arginine to ornithine, and release urea
arginase
___ and ___ link urea cycle to TCA
Asp; fumarate
overall rxn of urea cycle?
Asp+NH3+HCO3+3ATP–>urea+fumarate+2ADP+AMP+2i+PPi
__ ATP equivalents needed form each urea cule
4
organisms that release ammonia directly are usually ___ and are referred to as ____
aquatic; ammoniotelic
organisms that release uric acid (slightly water soluble) because can’t afford to lose water
reptiles, birds
reptiles and birds are examples of ____ organisms
uricotelic
major source of NH4?
dietary/body protein
in the liver, free ammonium produced from ________
serine, threonine, glutamine
in kidney, free ammonium gen by metabolism of glutamine by these enzymes:
glutaminase, glutamate dehydrogenase
ex. of monoamine that serve as hormone/neurotrans?
norepinephrine
how is blood ammonia left low?
formation of urea, form glutamate in muscle by glut dehydrogense, form glutamine in most tissues by glut synthetase
this condition shows how CNS particularly sensitive to ^ NH4
hyperammonemia
symptoms of hyperammonemia
tremors, slurring speech, blurred vision, cerebral edema, coma
glutamine is an ___ in astrocytes
osmolyte (brain swells)
glutamate is a substrate for synth of ____
GABA (gamma aminobutyrate)
2 causes of hyperammonemia?
liver damage (acquired), genetic (congenital)
liver damage can result from ____
viral hepatitis, hepatotoxins (alcohol)
compound administered that treats congenital hyperammonemia
phenylbutyrate (bind Glutamine)
in congenital hyperammonemia, why are defects in arginase less severe?
arginine contains 3 amino groups and can be excreted in urine
old treatment for congenital hyperammonemia?
inhibit protein intake, increase caloric intake in other things
a.a. catabolized to pyruvate or intermediate of TCA cycle are called?
glucogenic
a.a. catabolized to acetyl coA or acetoacetate are called?
ketogenic
the two exclusively ketogenic a.a.?
lysine, leucine
4 a.a. that channel to make pyruvate
Trp, Ala, Ser, Cys
path of Asn in mito?
Asn–>aspartate–>oxaloacetate
normal path of Phe?
Phe–>tyrosine–>acetyl coA/fumarate
PKU path of Phe?
Phe–>phenylpyruvate–>phenylacetate/phenyllactate
what is PKU?
phenylketonuria
symptoms of PKU?
mental retardation, fail to walk/talk, seizure, tremor, fail to grow, light skin/hair
how to treat PKU?
diet restrict Phe, no aspartame
tyrosine is precursor for ___
melanin
path of valine, isoleucine, leucine?
–>branched chain aminotransferase–>alpha keto acids–>branched chain alpha keto acid dehydrogenase complex–>acyl CoA derivatives
interference with dehydrogenase complex cause ____ disease
maple syrup urine
medical condition involving defect in tyrosine–>melanin enzyme
albinism
Four pyrrole rings linked together, with varying sidechains
porphyrin
porphyrins derive C and N from _____
glycine and succinyl CoA
porphyrin mainly binds :
Fe 2/3+
most common porphyria that is autosomal dominant, triggered by fasting/insufficient carbs (on IV)–>symptoms include abdominal pain, motor weakness, neuropsych prob
acute intermittent porphyria
porphyria that is characterized by red urine, teeth fluoresce red in UV, skin sensitive to light, anemic; associated with vampire myth
porphyria cutanea tarda
catecholamines are synthesized from ____
tyrosine
examples of catecholamines?
dopamine, norepinephrine, epinephrine
molecule that mediates many allergic/inflammatory responses, is a strong vasodilator, and is formed from decarboxylated histidine
histamine
found in intestinal mucosa and in CNS, mediates a sense of well-being, converted to melatonin, synthesized from tryptophan
serotonin
synthesized from glycine, guanidino group of arginine and methionine; when phosphorylated it is a high energy compound found in muscle and serves as short term energy source
creatine
On average, we eat ___g of glutamate from protein sources and ___g from MSG
13; 0.6
overall reaction of nitrogen cycle?
N2+10H+16ATP+8e–>2NH4+H2+16ADP+16Pi
forms of nitrogen available to plants:
ammonium, nitrates
______ provide entry points for assimilation of ammonium into biomolecules
glutamate and glutamine
inhibitors of glutamine synthetase:
glycine, alanine, CTP, histidine, glucosamine 6-P, AMP, Tryptophan, carbamoyl P
glutamine synthetase is regulated by _____
allosteric effectors (8 of them) covalent mods
all inhibitors of glutamine synthetase contain ____
Nitrogen
adenylylation occurs on ___ residue
tyrosine
What is SAM and what does it do?
S-Adenosylmethionine; for 1-C transfers to N and O atoms (eg. norepinephrine –> epinephrine)
Diet folate–>DHF–>THF need ____ to catalyze and ____ as reducing agent
DHFR; NADPH
1C transfers using THF
methionine synth, serine synth
all aa synth from intermediates of _______ pathways
TCA, PPP, glycolytic
nonessential amino acids:
alanine, asparagine, aspartate, glutamate, serine
why are some a.a. conditionally essential?
during illness (nutritional insult), in young developing animals (high requirement)
4 types of feedback inhibition
product inhibition, sequential, concerted, enzyme multiplicity
