amino acid oxidation II Flashcards
1
Q
in what form does the amino nitrogen leave the body in aquatic vertebrates
A
as NH4+ (ammonium)
2
Q
in aquatic vertebrates, amino nitrogen leaves as ammonium, but isn’t this toxic? explain
A
the toxicity is irrelevant, as NH4+ is immediately diluted in surrounding water
3
Q
in what form does the amino nitrogen leave the body in terrestrial vertebrates (mammals)
A
urea
4
Q
benefit of nitrogen being excreted as urea?
A
minimizes water loss
5
Q
in what form does the amino nitrogen leave the body in reptiles and birds
A
uric acid
6
Q
benefit of nitrogen being excreted as uric acid?
A
minimizes water loss
7
Q
which organ does the urea cycle occur in
A
liver
8
Q
where in hepatocytes does the urea cycle occur
A
mito and cytosol
9
Q
urea cycle: what molecule does the pre-step form
A
carbamoyl-phosphate
10
Q
urea cycle: what molecule does step 1 form
A
citrulline
11
Q
urea cycle: what molecule does step 2 form
A
argininosuccinate
12
Q
urea cycle: what molecule does step 3 form
A
arginine
13
Q
urea cycle: what molecule does step 4 form
A
urea
14
Q
pre step: what molecule are we starting with
A
NH4+
15
Q
pre step: describe what happens to NH4+ in the hepatocyte matrix. What does it convert to and what does this require?
A
NH4+ and bicarbonate join to form carbamoyl phosphate
16
Q
how many carbons is carbamoyl phosphate
A
1
17
Q
pre step: T or F: since ammonia and bicarbonate join to form carbamoyl-phosphate, there must be lots of bicarbonate in the mito matrix
A
true
18
Q
pre step: explain why there’s lots of bicarbonate in the hepatocyte matrix
A
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
19
Q
pre step: describe what can happen once carbamoyl-phosphate is formed
A
carbamoyl-P can donate it’s carbamoyl to ornithine
20
Q
T or F: ornithine is proteinogenic
A
false; it’s non-proteinogenic
21
Q
what amino acid is ornithine derived from
A
glutamate
22
Q
step 1: what molecule(s) do we start with
A
carbamoyl and ornithine
23
Q
step 1: describe what reaction occurs
A
carbamoyl and ornithine generate citrulline
24
Q
step 1: T or F: citrulline is proteinogenic
A
false; it’s non-proteinogenic
25
step 2: how many carbons is citrulline
6
26
step 2: what happens to citrulline once it's formed in the matrix
it leaves the matrix and enters the cytosol
27
step 2: what molecule do we start with
citrulline
28
step 2: describe the reaction that occurs
citrulline undergoes a 2-step conversion to argininosuccinate
29
step 2: what is the purpose of argininosuccinate production
it introduces the second amino group that's eventually found in urea
30
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
31
step 2: how many amino groups does argininosuccinate have
4
32
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)
33
step 2: argininosuccinate is a structural combination of which two molecules
succinate (CAC intermediate) and arginine (proteinogenic amino acid)
34
step 3: what molecule do we start with
argininosuccinate
35
step 3: where in the cell are we
cytosol
36
step 3: describe the reaction that occurs
argininosuccinate is cleaved to make free arginine and fumarate
37
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
38
step 4: what molecule(s) do we start with
arginine and fumarate (but fumarate isn't important)
39
step 4: describe the reactions that occur
water is added to arginine to form ornithine. Urea is displaced
40
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
41
step 4: what happens to ornithine once it's formed
it returns to the mito matrix for another round of the cycle
42
what enzyme converts ammonia and bicarbonate to carbamoyl-phosphate
carbamoyl-phosphate synthetase I
43
what enzyme converts carbamoyl and ornithine to citrulline
ornithine transcarbamoylase
44
what enzyme converts citrulline to argininosuccinate in a two step conversion
argininosuccinate synthetase
45
what enzyme cleaves argininosuccinate to arginine and fumarate
argininosuccinase
46
what enzyme adds water to arginine to form ornithine
arginase
47
what two things is the urea cycle regulated based on
amount of protein in the diet + frequency/timing of eating
48
most regulation of the urea cycle is through activity and expression levels of ___________________
urea cycle enzymes
49
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
50
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
51
which molecule is an intermediate of both the urea cycle and the CAC
fumarate
52
why can the urea cycle + CAC be easily linked
fumarate is an intermediate of both
53
between which parts of the cell do the urea cycle and CAC communicate
mito matrix and cytosol
54
what is the name of the cycle that physically links the urea cycle and the CAC
aspartate argininosuccinate shunt
55
what is the a-keto acid of aspartate? where is this molecule found?
OAA is the a-keto acid. It's a CAC intermediate
56
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
57
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
58
how many ATP total are required for the urea cycle
4
59
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
60
what is the NET cost of ATP in the urea cycle
1.5 ATP per turn
61
purpose of the malate-aspartate shuttle?
get NADH produced by glycolysis/cytosolic processes into the mito matrix (it lacks a transporter)
62
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)
63
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)
64
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
65
malate-aspartate shuttle: by which transporter does aspartate leave the mito matrix
aspartate-glutamate transporter
66
what is the net effect of the malate-aspartate shuttle
brings NADH from the cytosol into the matrix (shifts the location of NADH)
67
malate-aspartate shuttle: now that aspartate is in the cytosol, what are its two fates?
1. return to the CAC via OAA and the malate-aspartate shuttle, and bring reducing equivalents to the mito
2. enter the urea cycle by helping form argininosuccinate, producing fumarate as a byproduct for the aspartate-argininosuccinate shunt
68
after the urea cycle, what happens to all the leftover carbon skeletons
all are degraded into CAC intermediates
69
in which tissue types does carbon skeleton degradation occur
extra-hepatic tissues
70
why does carbon skeleton degradation occur in extra-hepatic tissues
this is where we need the fuel
71
list the 7 intermediates that can be formed via carbon skeleton degradation
pyruvate
acetyl-CoA
acetoacetyl-CoA
a-Kg
succinyl-CoA
fumarate
OAA
72
once carbon skeletons are degraded to CAC intermediates, list the 3 fates
1. end products are completely oxidized to CO2
2. end products are diverted from CAC for GNG
3. end products are diverted from CAC for ketogenesis
73
define ketogenic
making of ketones from degradation of amino acids
74
define glucogenic
making of glucose from degradation of amino acids
75
T or F: degradation of a few amino acids can be ketogenic or glucogenic
true
76
T or F: almost all amino acids are glucogenic when degraded
true
77
which two amino acids are strictly ketogenic
leucine and lysine
78
which amino acids are both ketogenic and glucogenic
isoleucine, Phe, Trp, Thr, Tyr
79
which amino acids are degraded to pyruvate (6)
Ala, Cys, Gly, Ser, Thr, Trp
80
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
81
which 7 amino acids are degraded to acetyl-CoA
Iso, Leu, Lys, Phe, Thr, Trp, Tyr
82
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
83
what does PKU stand for
phenylketonuria
84
what is PKU
a genetic defect in Phe degradation
85
which step of Phe degradation is disturbed in PKU? how?
defective enzyme in the first step of Phe degradation: Phe to Tyr
86
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
87
symptoms of PKU?
seizures, microcephaly, delayed development, behavioral problems, hyperactivity
88
how do you combat PKU
keep Phe levels very low
89
T or F: in PKU patients, a normally rare pathway becomes active to deal with the high Phe levels in the blood
true
90
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
91
list some dietary restrictions of someone with PKU
no nuts, no aspartame, no corn/kale/peas/rice
92
how does one get albinism
results from an inability to degrade tyrosine into melanin
93
melanin is a derivative of which amino acid
tyrosine
94
describe how PKU relates to albinism
PKU patients often have albinism, because Phe can produce tyrosine, which is required for melanin
95
which amino acids are degraded to a-KG
Arg, Glu, Gln, His, Pro
96
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
97
which amino acids are degraded to succinyl-CoA
Iso, Met, Thr, Val
98
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
99
which amino acids are degraded to OAA
Asp, Asn
100
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
