amino acid oxidation II Flashcards
in what form does the amino nitrogen leave the body in aquatic vertebrates
as NH4+ (ammonium)
in aquatic vertebrates, amino nitrogen leaves as ammonium, but isn’t this toxic? explain
the toxicity is irrelevant, as NH4+ is immediately diluted in surrounding water
in what form does the amino nitrogen leave the body in terrestrial vertebrates (mammals)
urea
benefit of nitrogen being excreted as urea?
minimizes water loss
in what form does the amino nitrogen leave the body in reptiles and birds
uric acid
benefit of nitrogen being excreted as uric acid?
minimizes water loss
which organ does the urea cycle occur in
liver
where in hepatocytes does the urea cycle occur
mito and cytosol
urea cycle: what molecule does the pre-step form
carbamoyl-phosphate
urea cycle: what molecule does step 1 form
citrulline
urea cycle: what molecule does step 2 form
argininosuccinate
urea cycle: what molecule does step 3 form
arginine
urea cycle: what molecule does step 4 form
urea
pre step: what molecule are we starting with
NH4+
pre step: describe what happens to NH4+ in the hepatocyte matrix. What does it convert to and what does this require?
NH4+ and bicarbonate join to form carbamoyl phosphate
how many carbons is carbamoyl phosphate
1
pre step: T or F: since ammonia and bicarbonate join to form carbamoyl-phosphate, there must be lots of bicarbonate in the mito matrix
true
pre step: explain why there’s lots of bicarbonate in the hepatocyte matrix
bicarbonate contains hidden CO2, so it’s very easy to make bicarbonate from CO2. There’s lots of CO2 in the matrix due to CAC
pre step: describe what can happen once carbamoyl-phosphate is formed
carbamoyl-P can donate it’s carbamoyl to ornithine
T or F: ornithine is proteinogenic
false; it’s non-proteinogenic
what amino acid is ornithine derived from
glutamate
step 1: what molecule(s) do we start with
carbamoyl and ornithine
step 1: describe what reaction occurs
carbamoyl and ornithine generate citrulline
step 1: T or F: citrulline is proteinogenic
false; it’s non-proteinogenic
step 2: how many carbons is citrulline
6
step 2: what happens to citrulline once it’s formed in the matrix
it leaves the matrix and enters the cytosol
step 2: what molecule do we start with
citrulline
step 2: describe the reaction that occurs
citrulline undergoes a 2-step conversion to argininosuccinate
step 2: what is the purpose of argininosuccinate production
it introduces the second amino group that’s eventually found in urea
step 2: describe the 2 steps that citrulline undergoes to form argininosuccinate
2a: 2 ATP used to make AMP-bound citrulline
2b: displacement of AMP by aspartate, which comes with its own amino group
step 2: how many amino groups does argininosuccinate have
4
step 2: aspartate is used in the 2 step conversion of citrulline to argininosuccinate. Where does all this aspartate come from?
comes from the hepatocyte mito matrix, where it was transaminated from glutamate (which is plentiful)
step 2: argininosuccinate is a structural combination of which two molecules
succinate (CAC intermediate) and arginine (proteinogenic amino acid)
step 3: what molecule do we start with
argininosuccinate
step 3: where in the cell are we
cytosol
step 3: describe the reaction that occurs
argininosuccinate is cleaved to make free arginine and fumarate
step 3: relevance of fumarate? (hint: isn’t argininosuccinate a combo of succinate and arginine?)
fumarate is the CAC intermediate following succinate. They are very similar in structure
step 4: what molecule(s) do we start with
arginine and fumarate (but fumarate isn’t important)
step 4: describe the reactions that occur
water is added to arginine to form ornithine. Urea is displaced
step 4: what happens to the urea that’s formed by the addition of water to arginine
it’s displaced. Travels through the blood and to the kidneys to be excreted
step 4: what happens to ornithine once it’s formed
it returns to the mito matrix for another round of the cycle
what enzyme converts ammonia and bicarbonate to carbamoyl-phosphate
carbamoyl-phosphate synthetase I
what enzyme converts carbamoyl and ornithine to citrulline
ornithine transcarbamoylase
what enzyme converts citrulline to argininosuccinate in a two step conversion
argininosuccinate synthetase
what enzyme cleaves argininosuccinate to arginine and fumarate
argininosuccinase
what enzyme adds water to arginine to form ornithine
arginase
what two things is the urea cycle regulated based on
amount of protein in the diet + frequency/timing of eating
most regulation of the urea cycle is through activity and expression levels of ___________________
urea cycle enzymes
what happens if one of your urea cycle enzymes is deficient?
a protein-rich diet –> build up of toxic free NH4+ or of urea cycle intermediates in blood and urine. But sufferers still have to eat some protein to acquire essential amino acids that we can’t synthesize
when might someone want to take an arginine supplement
when enzymes earlier in the cycle are deficient. Arginine can help generate urea, complete the cycle, and eliminate at least some of the excess amino groups
which molecule is an intermediate of both the urea cycle and the CAC
fumarate
why can the urea cycle + CAC be easily linked
fumarate is an intermediate of both
between which parts of the cell do the urea cycle and CAC communicate
mito matrix and cytosol
what is the name of the cycle that physically links the urea cycle and the CAC
aspartate argininosuccinate shunt
what is the a-keto acid of aspartate? where is this molecule found?
OAA is the a-keto acid. It’s a CAC intermediate
If fumarate is a CAC intermediate, why does it get converted to malate in the cytosol after leaving the urea cycle and then enter the CAC as malate?
it doesn’t have a mito matrix transporter, but there IS a malate/a-KG transporter
where does the ATP cost come from in the urea cycle
2 ATP equivalents are used to make carbamoyl from bicarbonate. As well, 2 ATP equivalents are used to make argininosuccinate from citrulline
how many ATP total are required for the urea cycle
4
how many ATP are indirectly produced due to the shunt? explain
2.5: fumarate from the urea cycle is converted to malate, enters the matrix, and produces NADH upon conversion to OAA during the CAC. NADH helps generate ATP in the ETC
what is the NET cost of ATP in the urea cycle
1.5 ATP per turn
purpose of the malate-aspartate shuttle?
get NADH produced by glycolysis/cytosolic processes into the mito matrix (it lacks a transporter)
NADH from which process is already in the matrix (malate-aspartate shuttle)
NADH produced by aspartate-argininosuccinate shunt is already in the right place (bc it will be used for the ETC)
malate-aspartate shuttle: how do we solve the problem of needing to bring the rest of the NADH into the matrix? (ie describe the steps of the shuttle)
take OAA in the cytosol, convert it to malate using NADH (reduction), ship malate across, convert malate back to OAA and NADH (oxidation)
malate-aspartate shuttle: once malate comes into the matrix and is oxidized to OAA and NADH, what happens to the OAA to complete the cycle
OAA is transaminated to aspartate (glutamate is the amino donor). Aspartate leaves the matrix, and is reconverted to OAA in the cytosol
malate-aspartate shuttle: by which transporter does aspartate leave the mito matrix
aspartate-glutamate transporter
what is the net effect of the malate-aspartate shuttle
brings NADH from the cytosol into the matrix (shifts the location of NADH)
malate-aspartate shuttle: now that aspartate is in the cytosol, what are its two fates?
- return to the CAC via OAA and the malate-aspartate shuttle, and bring reducing equivalents to the mito
- enter the urea cycle by helping form argininosuccinate, producing fumarate as a byproduct for the aspartate-argininosuccinate shunt
after the urea cycle, what happens to all the leftover carbon skeletons
all are degraded into CAC intermediates
in which tissue types does carbon skeleton degradation occur
extra-hepatic tissues
why does carbon skeleton degradation occur in extra-hepatic tissues
this is where we need the fuel
list the 7 intermediates that can be formed via carbon skeleton degradation
pyruvate
acetyl-CoA
acetoacetyl-CoA
a-Kg
succinyl-CoA
fumarate
OAA
once carbon skeletons are degraded to CAC intermediates, list the 3 fates
- end products are completely oxidized to CO2
- end products are diverted from CAC for GNG
- end products are diverted from CAC for ketogenesis
define ketogenic
making of ketones from degradation of amino acids
define glucogenic
making of glucose from degradation of amino acids
T or F: degradation of a few amino acids can be ketogenic or glucogenic
true
T or F: almost all amino acids are glucogenic when degraded
true
which two amino acids are strictly ketogenic
leucine and lysine
which amino acids are both ketogenic and glucogenic
isoleucine, Phe, Trp, Thr, Tyr
which amino acids are degraded to pyruvate (6)
Ala, Cys, Gly, Ser, Thr, Trp
once amino acids are degraded to pyruvate, what are the two fates
generate acetyl-CoA and enter the CAC, or generate OAA and undergo GNG
which 7 amino acids are degraded to acetyl-CoA
Iso, Leu, Lys, Phe, Thr, Trp, Tyr
once amino acids are degraded to acetyl-CoA, what are the two fates
acetyl-CoA can then generate ketone bodies or join OAA to make citrate in the CAC
what does PKU stand for
phenylketonuria
what is PKU
a genetic defect in Phe degradation
which step of Phe degradation is disturbed in PKU? how?
defective enzyme in the first step of Phe degradation: Phe to Tyr
PKU: what is the result of having a defective enzyme in the first step of Phe degradation
Phe builds up. Excessive Phe may outcompete other amino acids trying to pass the blood brain barrier, resulting in deficits of other amino acids in the brain
symptoms of PKU?
seizures, microcephaly, delayed development, behavioral problems, hyperactivity
how do you combat PKU
keep Phe levels very low
T or F: in PKU patients, a normally rare pathway becomes active to deal with the high Phe levels in the blood
true
describe the normally rare pathway that becomes active in PKU patients
amino group of Phe is donated to pyruvate to form alanine (transamination). These phenyl products then accumulate in the blood and are excreted in urine. Produces a musty odor
list some dietary restrictions of someone with PKU
no nuts, no aspartame, no corn/kale/peas/rice
how does one get albinism
results from an inability to degrade tyrosine into melanin
melanin is a derivative of which amino acid
tyrosine
describe how PKU relates to albinism
PKU patients often have albinism, because Phe can produce tyrosine, which is required for melanin
which amino acids are degraded to a-KG
Arg, Glu, Gln, His, Pro
describe how Arg is degraded to a-KG
arginine degradation releases urea and produces ornithine. Removal of the first amine group on ornithine requires a transamination that converts a-KG to glutamate
which amino acids are degraded to succinyl-CoA
Iso, Met, Thr, Val
describe how Iso, Met, Thr, Val are degraded to succinyl-CoA
they’re first degraded to propionyl-CoA, which can then be modified to succinyl-CoA with a mutase
which amino acids are degraded to OAA
Asp, Asn
describe how Asn and Asp are converted to OAA
Asn is converted to Asp by asparaginase, releasing NH4+. A transamination converts Asp to OAA. But to be used in the CAC, OAA must be converted to malate to enter the matrix. Or instead, OAA can be diverted to GNG in the liver cytosol
