oligo-peptides are proteolyzed by aminopeptidases on luminal surface
di and tri peptides are cleaved by peptidases in enterocytes
basic strategy of amino acid catabolism (2 steps)
1. remove amino group
2. remaining arbon skeletons are used:
energy - glucose, acetyl coA, TCA ints
2 fates of reomved amino groups
-converted to urea in the urea cycle
-used for synthesis of nitrogen containing compounds
1. amino transferase
1. transfer the amino group to an a-ketoacid (usually a-ketoglutarate) to yield glutamate
oxidative deamination to remove the amino group as an ammonium ion
by glutamate dehydrogenase
why transfer a-amino group to a-ketoacid/a-ketoglutarate?
many different amino acids funnel to a few for the next step.
two major amino transferases
asp + a-ketoglutarate <--> OAA + glutamate
ala + a-ketoglutarate <--> pyr + glutamate
these rxns can go in reverse as well
* 7 carbon skeleton metabolites / uses of carbon skeletons
P triple A sof
aminotransferases require what?
require the prosthetic group pyridoxal phosphate (PLP). vitamin B6 derivative
prior to amino acid binding...
Lysine makes schiff-base with PLP aldehyde,
acts as a place holder for incoming amino acid
amino acid displacs the Lysine.
glutamate is oxidized to form a schiff-base intermediate, then the amino group is hydrolyzed to yield a free ammonium ion and a-ketoglutarate.
NH4+ is toxic
reaction can use NAD+ or NADP+
can run forward or backward depending on concentrations of prods and reactan
GTP and ATP = inhibitors
GDP and ADP = activators
low energy state increases the enzymes actvity
___ and ___ can be directly deaminated
serine and threonine
serine --> pyruvate + NH4+
threonine --> a-ketoglutarate + NH4+
can use branched chain AA Ile, Leu, Val for fuel.
do not have urea cycle enzymes to process ammonium, send to liver as amino group on alanine (also glutamine)
ammonium excreted as ___ for most animals except
ammonium excreated as urea for most animals except birds, reptiles, amphibians
removal of excess nitrogen in aquatic animals and birds and reptiles?
aquatic - NH4+ releaesd to water directly
birds and reptiles - uric acid is excreted
urea structure - what come from what
first amino group comes from mmonia
second amino group comes from aspartate
carbon comes from bicarbonate
CO2 + NH4 --> carbamoyl phosphate
carbamoyl phosphoate + ornithine --> citrulline
cirtulline + aspartate --> arginosuccinate
--> arginine (+ fumarate)
arginine --> ornithine (H2O in, urea out)
rejoins with citrulline again in mit matrix.
7 common metabolic intermediates
aromatic amino acids
branched amino acids
transamination of branched chain amino acids
branched chain amino acid transaminase
a-ketoglutarate is the amine acceptor yielding glutamate and 3 different a-ketoacidds
branched chain: oxidation of a-ketoacids enzyme
branched chain a-ketoacid dehydrogenase complex
yields 3 different coA derivatives
3 different coA derivatives
acetyle coA and acetoacetyl coA
phenylalanineis hydroxylated to tyrosine by what enzyme
linearization of homogentisateto form maleylacetoacetate - wht enzyme
conversion of phenylalanine is one by phenylalanine hydroxylase which requires what electron carrier?
unlike FADH2 and NADH, not derived from a vitamin. we can make ourselves
mutation in phenylalaninehydroxylase
or insufficient conc of tetrahydrobiopterin.
phenylalanine breakdown insufficient or absent. high levels in blood (20x higher), phenylpyruvate and phenylacetate generated.
(normally 75% phenylalanine --> tyrosine)
screening of infants. neurologic and cognitive implications (-40 IQ) if untreated within 1st yr of life
mousy odor in urine and sweat due to phenylacetate accumulation,
restricted diet low in phenylalanineand high in tyrosine
absence of enzyme homogentisate oxigenase
buildup of homogenitase. excreted in urine, produces melanin when oxidized by air (black urine)
relatively benign disease because homogentisate can be excreted.
maple syrup urine disease
branched-chain dehydrogenasemissing or defective.
oxidative decarboxylation of a-ketoacids from branched chain AA (ile, val, leu) does not occur. buildup
toxic so causes mental deficiency, failure to thrive
screening in newborn blood sample
AA that are only ketogenic
leucine and lysine
both the L's
AA that are both ketogenic and glucogenic
Phe, Ile, Trip, Tyr
phil is triping on tires
higher organisms cannot take up nitrogen from the environment as N2 so
must rely on archae and bacteria which can fix Nitrogen - split N2 and reduce it to NH3
we ingest N containing compouds, break them down, and incorporate the nitrogen through the action of
glutamate dehydrogenaseand glutamine synthetase
bacteria can fix N even in the presence of O2 because
leghemoglobin sequesters O2 away from centers where N is fixed, so no H2O formed
this means bacteria can still run the ETC and ATP synthase
a-ketoglutarate to glutamate
or vice versa
glutamate to glutamine
or vice versa
two major forms of glutamine synthetase
general cellular isoform - predominantly in liver, kidneys. 8-10 subunits in mammals, 12 in bacteria
neuronal isoform - found in astrocytes, constitutively active (always on). protection against high ammonia levels that cause neuronal swelling/cognitive impairment, aids in recycling of glutamate a neurotransmitter
glutamine synthetase structure
12 identical subunits
(8-10 in mammals)
negative feedbak of glutamine synthetase
by alanine and glycine
binding of each product finely tunes each enzyme. as each binds, turns down a ltitle more
change in one conformation an affect the other subunit
de-adenylated Tyr residues = active, adenylated Tyr = less active
name the essential amino acids
threonine --> a-ketobutyrate
fights reactive oxygen species
___ is the primary activator of methyl gorups for methyl transfer
methylation of SAM and hydrolysis of adenosyl group produces homocysteine
_____ can transfer a methyl group to homocysteine to produce methionine.
high levels of _____ are associated with increased risk for coronary heart disease and arteriosclerosis, endothelial damage, exidative stress, increase in vascular smoot muscle tissue
defieicny in ____ is thought to be a factor in the build up of serum homocysteine
vitamin therapy (B6, B12 and folate), necessary for formation of cysteine and methionine to draw away homocysteine through synthesis of these amino acids
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