Exam 2 Ch 21 Flashcards
1
Q
Ch 21 content
A
amino acid metabolism
2
Q
what is the oxidizing agent in glycolysis
A
NAD+
3
Q
what is the pentose phosphate pathway for
A
regeneration of NADPH
4
Q
where does the oxidation of fatty acids happen
A
mitochondria, long ones in the peroxisomes
5
Q
Protein degredation occurs to do what?
A
store nutrients
eliminate abnormal proteins
regulate metabolism
6
Q
where do proteins get degraded
A
lysosome and cytosol
7
Q
what’s the pH of the cytosol and the lysosome
A
7.4
5
8
Q
Ubiquitin-activating enzyme
A
E1. Most organisms only have one type
9
Q
ubiquitin-conjugating enzyme
A
E2 organisms have multiple copies
10
Q
ubiquitin-protein ligase
A
E3 organisms have multiple copies, interact with one or more E2s
11
Q
WHat does ubiquitin do
A
marks proteins for degradation in eukaryyotes
12
Q
What do E1 2 and 3 do when they interact with each other
A
pass ubiquitin onto each other
13
Q
What does efficient protein degradation require
A
at least 4 tandemly linked ubiquitin. They can contain 50+ ubiquitin units in a polyubiquitin chain
14
Q
What are the ubiquitin polyubiquitin chains linked to?
A
The R group of a K
15
Q
How do prokaryotes mark proteins for degredation
A
Pup: prokaryote ubiquitin-like proteins
16
Q
Which amino acids have half-lives of 2-3 minutes
A
N-terminal residues D, R, L, K and F
17
Q
Which have half lives longer than 10 hours in prokaryotes and longer than 20 hours in eukaryotes
A
A, G, M, S, T (very hydrophobic)
18
Q
PEST proteins do what?
A
rapidly degraded in eukaryotes. Series of amino acids.
19
Q
What’s the most common proteosome in mammals
A
26S.
20
Q
What are the two parts of 26S proteosome
A
19S: binds ubiquinated proteins, unfolds the protein (requires ATP), moves along 19S cap and discards the ubiquinone
20S: hydrolysis of unfolded proteins
21
Q
Which part of 26S is ATP dependedn
A
19S
22
Q
what are the functions of the alpha and beta subunits of 26S: 20S part
A
alpha subunits are regulatory
Beta are proteolytic: cleave amino acids into 8 unit segments (3 of them, acidic, basic, hydrophobic)
23
Q
WHat does S stand for in 26S
A
sedimentation coefficient of Svanbergs
24
Q
Where does the carbon skeleton of the broken amino acid go?
A
COs and H2O
Glucose
X
X
25
Hydrolysis mechanisms of protease classes
1.serine
2.cysteine
3. aspartyl
4. metalloproteases
5. glutamic
6. threonine
26
Self-cleaving mechanisms
Asparagine
27
what is the common amino acceptor and what does it turn into
alpha-ketoglutarate
glutamate
28
what is transaminases cofactor
PLP which is vitamin B6
29
How do transaminases work
they crosslink to their amino acid and forms a schjiff base
30
what does stages 1 on transaminase mechanism do
converts an amino acid to an alpha-keto acid
31
steps in stage 1 of transaminase mechanism
transamination: amino group attacks schiff-base, lys leaves
Lys-catalyzed tautomerization of Calpha proton moves to Cbeta
base-catalyzed hydrolysis. water attacks cleaving bond
32
what is stage 2 of transaminase mechanism
converts alpha keto acid to amino acid. Reversal of stage 1
33
what allosterically inhibits GDH
GTP and NADH
34
what allosterically activates GDH
ADP and NAD+
35
how many ATP does the transfer of ammonia to urea take
3, costly
36
what are the five enzymes in the urea cycle ?
1. Carbamoyl phosphate synthetase
2. Ornithine Transcarbamoylase
3. Argininosuccinate Synthetase
4. Argininosuccinase
5. Arginase
37
Carbamoyl phosphate synthetase?
ammonia + bicarbonate + ATP ~> Carbamoyl
38
Ornithine Transcarbamoylase?
carbamoyl + Ornithine ~> Citruline
39
Argininosuccinate Synthetase?
Citruline + Aspartate + ATP ~> Argininosuccinate
40
Argininosuccinase?
Argininosuccinase ~> Arginine + Fumarate
41
Arginase?
Arginine + H2O ~> XXX
42
What is the most important step
Carbamoyl phosphate synthetase. Commites ammonia into the urea cycle
43
What are the two isoforms of CPS (carbamoyl phosphate synthetase)
mitochondrial CPS I and Cytosolic CPS II
44
Mechanism of CPS
ATP phosphorylates bicarb to carboxyphosphate. Ammonia attacks arboxyphosphate making carbamate. Second ATP phosphorylates carbamate to carbamoyl phosphate
45
ASS mech
acquires the second urea nitrogen.
1. ATP activates the ureido oxygen via citrullyl-AMP formation
2. Aspartate amine displaces AMP (costs 2 phosphyanhydride bonds)
46
proteases classes
Serine (Ser)
Cysteine (Cys)
Aspartyl (water)
Metalloproteases
Glutamyl
Threonine (Threonine first vs methyonine)
Asparagine
47
Are transaminases highly reversible
yes
48
Is glutamate dehydrogenase reversible or irreversible?
Irreversible
49
Where do the two moles of nitrogen from
upstream amino acid and aspartate
50
When glutmate concentrations increas what does that mean
amino acid catabolism via transminases
51
What does increase glutamate concentrations stimulate
NAG synthesis
52
Amino acid catabolism acounts for what percent of metabolic energy in animasl
10-15%. The 20 break down into 7 in intermediates
53
WHat are the 7 intermediates that amino acids break down into
1. pyruvate
2. oxoglutarate
3. succinyl-CoA
4. Fumarate
5. Oxaloacetate
6. Acetyl-CoA
7. Acetoacetate 8
54
What are the two pathways the amino acid metabolites go through
Glucogenic (metabolites 1-5)
Ketogenic (6-7)
55
what does aminotransferase yield
Pyruvate
56
What does serine-threonine dehydratase eliminate
Ammonia
57
HOw many enymes are in the glycine cleavage system
4
58
WHat happens in the threonin dehydrogenase
oxidation of Alcohol to a ketone
59
Pathway of N & D degradad to Oxaloacetate
Aspartate transmination yield oxaloacetate.
60
Pathway of R, E, Q H, P and degraded to oxoglutarate
1. Glutamate dehydrogenase
2. Glutaminase
3. Arginase
4. Ornithine-delta-aminotransferase
5. Glutamate-5-semialdehyde dehydrogenase
6. proline oxidase
7. Nonenzymatic Hydration
8. histidine ammonia lyase
9. urocanate hydratase
10. Imidazolone propionase
11. Glutamate formiminotransferase
61
WHAT ARE THE thf CONVERSIONS
Ser to Gly
Gly to Co2 & NH3
3. His to GLu
62
What are L and K degraded to
Acetyl CoA & Acetoacetate
63
What is W degraded to
Ala
64
THree typ (W) pathways
Kynurenine, serotonin, indole
65
What are the three W pathways dependent on ?
Heme
66
What are Y and F degraded to form
Fumarate and Acetoacetate
67
What is a Pterin?
similar to Flavin. Redox cofactor
68
WHat do we synth A, N, D, E, Q from?
pyruvate, oxaloacetate, and oxoglutarate
69
What is the precursor to P and R
E
70
What are S, C & G derived from ?
3-Phosphoglycerate
71
What are K, M & T synthesized from?
D. Plants and animals
72
What are L, I & V derived from?
Pyruvate
73
What are F, T, and W synthesized by
glucose derivatives
74
What are the essential amino acids
RHILMFTWV
75
WHat are the non-essential amino acids?
ANDCEQGPSY
76
Should I memorize which amino acids are essential and non-essential?
77
What amino acids are synthesized from pyruvate, oxaloacetate, and oxoglutarate
A, N, D, E, Q
78
WHat amino acids are synthesized from E
P, R, O
79
What amino acids are synthesized from 3-Phosphoglycerate?
S, C, G
80
What amino acids are syntehsized from D
k, m, t
81
What amino acids are branch chained
L, I, V
82
What amino acids are only synthesized from pyruvate
L, I, V
83
What amino acids are synthesized from glucose derivatives?
F, Y, W
84
How is H synthesized
Nucleotide biosynthesis.
85
What is Heme synthesized from
G & Succinyl-CoA
86
What kind of pathway is the synth of heme
protoporphyrin-dependent pathway
87
What are the Uroporphyrinogen III branch?
Cobalamin
Siroheme
Coenzyme F430
88
What are the two heme pathways?
Shemin pathway to the protoporphyrin dependent pathway
and
C5 Pathway to the coproporphyrin dependent pathway
89
Where does acetyl group come from
glucose
90
Half-life of hemoglobin
120
91
What does heme degredation yield
biliverdin then bilirubin
92
What are IsdG/I, MhuD, and HO pathways
Heme degredation pathways. Heme oxygenase, iron surface determinant, mycobacterial geme utilization
93
What heme degredation pathway does staphylococcus aureus use?
Iron sulface determinant G & I
94
Mycobacterium Tuberculosis uses
MhuD pathway
95
Most organisms use what heme degredation pathway
Heme Oxygenase pathway
96
Why can't we just remove the heme from the circle
too thermodynamically uphill. Have to break the circle to destablize it
97
What is nitric oxide (NO) derived from
R
97
What does Nitric oxide synthase (NOS) catalyze
conversion between Arg & Citrulline
97
What are other sources of NO in out body
S-nitrothiols and nitrite and nitrate
98
What's the point of protein degradation
store nutrients, eliminated misfoled or denatured, regulating by eliminating superfluous enzymes.
99
Difference between short and long lived enzymes.
Short lived: vital metabolic control points, long lived: nearly constant catalytic activity under all physiological conditions.
100
What does uniquitin do in degradatino?
marks eukaryotes for degedation.
101
Which ubiquintin enzymes do organisms have multiple copies of?
2. Ubiquitin-conjugating enzyme
3. Ubiquitin-protein ligase
The one they don't is the first one, ubiquitin-activating enzyme
102
Where is RING protein involved?
Ubiquitin marking, E3 ligase. there are 616 of them in humans.
103
What is HECT and where is it involved
Eukaryotic ubiquitin enzyme E3 ligase. There are 28 in human genome.
104
How many tandem linked ubiquitins are needed for efficient proterin degredation and how many can there be total
4 are needed
50+ potentially
105
What is Pup
prokaryotic ubiquitin like proteins
106
What is the N-end rule and what does it apply to
amino acids at the N-terminus (the start) of the protein affects how long the protein lives
it applies to pro and euk
107
What is the half live of proteins with N-terminal residue D, R, L, K, F?
2-3 min
108
What is the half live of proteins with N-terminal residue A, G, M, S, T, V
>10 min (longer in eukaryotes)
109
What are PEST proteins and waht do they do
they are proteins rich in P, E, S, and T and they signal for rapid degredation
110
What breaks down proteins tagged by ubiquitine in mammals?
26S proteasome
111
What does this 26S Proteasome contain?
19S Cap (gatekeeper and process center)
and 20S Core (cylindrical chamber)
112
What does the S mean
Svedberg unit, it measures size/speed of particle in centrifugation
113
Function of the 19S Cap
binds, unfolds, removes ubiquitin (ATP needed)
114
what does the 20S core do
degrades protein into short peptides
115
What is B1, B2, B3
part of the 20S core, cuts proteins at sites that are
acidic
basic
hydrophobic
116
What are the two pathways for protein degradation
Lysosomes and ubiquitin-proteosomes
117
When are lysosomes selective and nonselective for degredation
normally non selective under physiological condition. Selective for KFERQ proteins during starvation.
118
lysosomes become more selective under starvation condition and select for KFERQ what is this called
chaperone-mediated autophagy
119
What does E1 (activation) do?
priming ubiquitin via ATP
120
What does E2 (conjugation) do?
transferring ubiquitin to a protein selector complex
121
WHat is E3 (ligation)
attaching ubiquitin to a protein for degredation
122
After the protein is marked, where does it go?
Proteosome! protein shredder. It hydrolyzes polyubiquitinated protein. 26S -> 19S-20S-19S
123
What are amino acids broken down into?
NH3 and carbon skeleton
124
Where does the NH3 from amino acid degredation go to
urea
125
What does the carbon skeleton from amino acid degredation broken to
CO2 +H2O, glucose, acetyl-CoA, and ketone bodies
126
what is deamination
removal of a -NH2 group
127
What is deamination done by?
transaminases. Transfers the NH2 group
128
what is the carbon skeleton left behind from ddeamination called
alpha-keto acid like pyruvate
129
what is the common amino accid acceptor. Hint: TCA intermediate
alpha ketoglutarate
130
What is the transaminase mechanism?
Stage 1: converts an amino acid to an alpha-keto acid
Stage 2: converts an alpha-keto acid to an amino acid (reversal of stage 1)
131
Name the five steps of the urea cycle in order
1. Carbamoyl phosphate synthetase (carbamoyl)
2. Ornithine Transcarbamoylase (citruline)
3. Argininosuccinate Synthetase (argininosuccinate)
4. Argininosuccinase (arginine + fumarate)
5. Arginase (urea + Ornithine)
132
What are the reagents beginning the urea cycle?
Ammonia + Bicarbonate + ATP -> Carbamoyl
133
What are the final products of the urea cycle (5. Arginase)
Urea + Ornithine
134
what are the two isoforms of eukaryotes of Carbamoyl Phosphate Synthetase (which catalyzes the committed step into urea cycle
Mitochondrial CPS I (ammonia is nitrogen donor)
Cytosolic CPS II (glutamine in nitrogen donor)
Prokaryotes only have one CPS and it does the function of CPS I and II
135
What are the mechanistic steps of CPS
1. first ATP phosphorylates bicarbonate to carboxyphosphate
2. ammonia attacks carboxyphosphate, displacing phosphate yielding carbamate
3. Second ATP phosphorylates carbamate to carbamoyl phosphate
136
What is ASS
Argininosuccinate Synthetase (second enzyme in the urea cycle)
137
What is the mechanism for ASS
1. ATP activates the ureido oxygen via citrullyl-AMP formation
2. Aspartate amine displaces AMP
o Two phosphoanhydride bonds are broken
138
Which protease class is self-cleaving?
Asparagine
Asn
139
For transamination and deamination, which one is highly reversible and which is irreversible
Transaminases are reversible and glutamate dehydrogenase is irreversible
139
What is the immediate precursor of urea
arginine amino acids
140
What happens in step 5 of urea
Arginase hydrolyzes arginine to urea
141
What happens along with urea being subsequently secreted in the arginase step 5 of urea
ornithine & citrulline cross the IMM
142
What takes ornithine and citrulline across the IMM during the fifth step of urea
human ornithine/citrulline carrier (hORC). Catalyzes electroneutral exchange
143
How does the urea cycle get started/ what activates CPS
N-acetylglutamate (NAG). NAG is made from glutamate and acetyl-CoA
144
Why does glutamate concetntraions increase?
as a result of catabolism of amino acids via transaminases. Increased glutamate concentrations stimulate
NAG synthesis
CPS is subsequently upregulated, stimulating
the Urea Cycle
145
These pathways are BLANK
1. Pyruvate
2. Oxoglutarate (α-ketoglutarate)
3. Succinyl-CoA
4. Fumarate
5. Oxaloacetate
Glucogenic
145
These pathways are BLANK
6. Acetyl-CoA
7. Acetoacetate
Ketogenic
146
Which amino acids are degraded to pyruvate?
A, C, G, S, and T
146
What amino acids are degraded to Oxaloacetate?
N and D
147
What amino acids are degraded to oxoglutarate?
R, E, Q, H and P
148
What amino acids are degraded to Succinyl-CoA?
M, T, I and V
149
Which amino acids are degraded to Acetyl-CoA and Acetoacetate
L and K
150
what amino aced is degraded to Ala, Acetoacetate, and NAD+
W
151
what amino acid is degraded to fumarate and acetoacetate?
Y and F
152
What is Tetrahydrofolate Cofactors (THF) made from
folic acid (vitamin B9)
common THF conversions are
Ser to Gly
Gly to CO 2 & NH3
His to Glu
153
Where is the Kynurenine pathway seen?
The degredation of W to ala and acetoacetate and NAD+
154
What does the final product of A, C, G, S, T metabolism feed into?
Gluconeogenesis because pyruvate is produced
155
What does the final product of N, D metabolism feed into?
TCA Cycle because oxaloacetate is produced
156
What does the final product of R, E, Q, H, P metabolism feed into?
TCA Cycle because alph-ketoglutarate is made
157
What does the final product of M, T, I, V metabolism feed into?
TCA cuz succinyl-CoA is made
158
What does the final product of L, K metabolism feed into?
Ketogenesis cuz acetyl-CoA and Acetoacetate
159
What does the final product of Y, F metabolism feed into?
TCA and Ketogenesis cuz fumarate and acetoacetate are produced
160
What does the final product of W metabolism feed into?
Glucogenesis and Ketogenesis because ala, acetoacetate, and NAD+ are made
161
What are A, N, D, E, and Q synthesized from?
Pyruvate, Oxaloacetate, and Oxoglutarate are
162
What does P, R, and Ornithine come from?
E
163
What are S, C, and G derived from?
3-phosphoglycerate
164
What are K, M and T syntehsized from?
D
165
Which amino acid biosynth is cobalamin dependent?
Methionine synthase in K, M, and T
166
What are L, I, and V derived from?
Pyruvate is
167
What amino acid building pathway is TPP Dependent?
L, I, and V
168
WHat are F, Y and W syntehsized from?
Glucose derivatives. Phosphoenolpyruvate + erythrose-4-phosphate. PLP dependent
169
Which amino acid building group is PLP dependent
F, Y, and W
170
What is H derived from?
an intermediate nucleotide biosynthesis. the key intermediate is imidazole glycerol phosphate
171
Are these the essential or non essential amino acids? R, H, I, L, M, F, T, W, V
Essential
172
Are these the essential or non essential amino acids? A, N, D, C, E, Q, G, P, S, Y
Non-essential amino acids
173
What is Heme synthesized from?
G and Succinyl-CoA
174
where does heme go when degrated
it yields bilirubin. it is tranferred through the blood via albumin, and secreted with bile
175
What is Nitric Oxide derived from?
R
