Chapter 22 Flashcards
(72 cards)
1
Q
Nitrogen conservation
A
most organisms are very conservative in how they use their nitrogen
2
Q
Free amino acids and nucleotides
A
often salvaged and reused
3
Q
Main source of nitrogen
A
the air, 80% N2
*we can’t use, bacteria can
4
Q
Nitrogen cycle
A
- fixation
- nitrification
- denitrification
5
Q
Fixation Overview
A
- in some bacteria
- fixes atmospheric N2 to yield ammonia
6
Q
Nitrification
A
- in bacteria
- ammonia from soil converted to nitrate
7
Q
Plant nitrification
A
some plants take up and reduce nitrate in the soil and produce ammonia for their own use in amino acids and nucleotides
8
Q
Animal nitrogen sources
A
often plants
9
Q
Denitrification
A
- some bacteria
- convert nitrates back to N2
10
Q
Nitrogen Fixation
A
- exergonic
- high activation energy because of stable triple N-N bond
- facilitated by ATP
- requires other things
11
Q
Nitrogen Fixation Requirements
A
- 8 electrons
- 6 for reduction of N2
- 2 to make H2
12
Q
Ammonia incorporation
A
assimilated into amino acids then other molecules
13
Q
Glutamate
A
main source of amino groups thru a.a. oxidation via transamination
14
Q
Glutamine
A
main source of amino groups for biosynthetic processes
15
Q
Glutamine synthetase
A
-catalyzes ammonia and glutamate to make glutamine
16
Q
Glutamine transfer in mammals
A
ammonia must be transferred by glutamine because glutamate has a large negative charge
17
Q
Glutamine in the liver
A
liberated to form glutamate to feed the urea cycle or is reused for amino acid biosynthesis
18
Q
Allosteric regulation of glutamine synthetase
A
- primary point of entry for reduced N2
- primary point of regulation
- > 6 products of glutamine metabolism, glycine and alanine inhibit
- effect is “more than additive”
19
Q
“more than additive” inhibition
A
multiple allosteric binding sites for multiple effectors
20
Q
Amidotransferase mechanism
A
- glutamine amidotransferase
- Cys acts as a nucleophile and cleaves the amide bond and channels it to the other substrate
21
Q
Glutamine amidotransferase
A
catalyzes the transfer of amine from one substrate to another
22
Q
Amino acid derived intermediates
A
all a.a’s are derived from intermediates in glycolysis, citric acid cycle or the pentose phosphate pathway
23
Q
Nonessential amino acids
A
- 11
- we make
24
Q
Essential amino acids
A
- 9
- mostly non polar
- obtained from the diet
25
From glycolysis
- 3 phosphoglycerate
- phosphoenolpyruvate
- pyruvate
26
From pentose phosphate pathway
- ribose 5-phosphate
| - erythrose 4-phosphate
27
From citric acid
- alpha ketoglutograte
| - oxaloacetate
28
alpha ketoglutarate in E coli
- P, E, R, Q
- makes E by transamination
- E can be converted to Q
- E can be cyclized to form P using 3 enzymes and 2 reductions
- E can be converted to R via ornithine and the urea cycle in bacteria
29
3-phosphoglycerate in humans
- 3-PG is oxidized and gets an amino group from E, then is hydrolyzed to make S
- methylene group transferred to THF to make G
- use S and get sulfur from Met
30
Oxaloacetate
- T from transamination from glutamate
| - N amidation of Asp using NH4+ from Q
31
Branching point between Lys and either Met or Thr
Aspartate beta-semialdehyde
32
Branching point between Met and Thr
Homoserine
33
Interconnected biosynthesis in oxaloacetate
Lys, Met, Thr, Iso, Val and Leu are all interconnected
34
Pyruvate
- A from pyruvate and transamination from E
- I and V share 4 common enzymes
- L is made from an intermediate in the V pathway
35
Interconnected biosynthesis in pyruvate
K, M, T, V, L, and I are interconnected
36
PEP and Erythrose 4-phosphate
- condense to form shikimate in 4 steps
- shikimate condensed into chorismate with another PEP and phosphate hydrolysis
- chorismate is branch point for Trp and Phe/Tyr
37
Chorismate to W
- gets amino group, loses pyruvate -> anthranilate -> condenses with PRPP ->cyclized to form indole ring
- tryptophan synthase
38
Tryptophan synthase
-releases glyceraldehyde 3-phosphate -> indole + serine -> Trp
39
Chromate to Y and F
- pyruvate group moved by a mutate to form prephenate
- prephenate dehydrogenase/dehydratase accepts prephenate branching into Tyr and Phe
- then transamination with E
- done in E coli
40
Ribose 5-phosphate
- > PRPP by ribose phosphate pyrophosphokinase
- His from:
- PRP, 5 carbons
- ATP, N and C
- E, 2nd nitrogen ring
- not made in humans
41
Inhibition of amino acid biosynthesis
- 1st reaction
- end products
- most responsive mechanism
42
1st reaction in each pathway
usually irreversible and catalyzed by an allosteric enzyme
43
End products of each pathway
negatively allosterically regulate to prevent formation of more product
44
Sequential feedback inhibition
* not common
- isozymes of protein are independently allosterically regulated
- prevents one product from stopping the synthesis of intermediates which are used for the production of a different product
45
Glycine in porphyrins
- common precursor
- in mammals glycine and succinyl-CoA make delta-aminolevulinate
- glutamate in plants not glycine
- 2 delta-alv condense and make porphobilnogen
- 4 porphobilnogen condense to make protoporphyrin
- chelates Fe2+ and makes heme
46
Porphyrins
- nucleus of 4 cyclic amines
| - in heme proteins like hemoglobin and cytochromes
47
Heme precursor to bile pigments
-damage/death of RBC's release heme ->degraded by heme oxygenase -> biliverdin -> bilirubin
48
Bilirubin
- bruises -> black/purple -> green (biliverdin) -> yellow (bilirubin) -> urobilin (yellow in urine) or stercobilin (red/brown in feces)
- impared liver fun or blocked bile secretion can cause leakage into blood -> jaundice
- newborns don't have enough of the enzyme to degrade -> jaundice
49
Aromatic amino acids are precursors o plant compounds
- Phe and Tyr are key components of plant polymer lignin
- Trp is precursor to plant growth hormone auxin
- Phe and Tyr give rise to alkaloids and flavorings (morphine, vanilla)
50
De Novo pathways
- synthesize nucleotides
| - uses amino acids, ribose 5-phosphate, CO2 and NH3 are precursors
51
Salvage pathways
- synthesize nucleotides
| - uses recycled free bases and nucleosides released from nucleic acid breakdown
52
Purines
G and A
53
De novo purine synthesis
- PRPP provides the ribose and phosphate
- amine transferred from glutamine
- 3 atoms from glycine
- formyl group from THF
- amine from glutamine
- ring closure to form imidazole ring
- C from bicarbonate
- N from aspartate
- formyl group from THF
- condensation closes 2nd ring forming inosinate
* takes a lot of ATP
54
Inosinate precursor to adenylate snd guanylate
- inosinate converted to adenylate (AMP) by addition of amino group from aspartate and loose of fumarate
- inosinate converted to guanylate (GMP) by NAD dependent oxidation to xanthanylate followed by addition of an amino group from glutamine
55
Feedback inhibition of purine synthesis
- end products; IMP, AMP, GMP inhibit run catalyzed by glutamine-PRPP amidotransferase
- AMO and GMP act synergistically
- AMP and GMP inhibit synthesis of branch point products of IMP
56
Pyrimidine
T and C
57
De novo pyrimidine synthesis
- transfer of carbamoyl group from carboxyl phosphate to the amine of apsartate followed by dehydration, cyclization and oxidation to form orotate.
- orotate + ribose 5-phosphate = uridylate (UMP)
- UMP phosphorylated to UTP
- CTO formed from UTP with glutamine as amine donor
58
Pyrimidine vs Purine synthesis
-in pyrimidine, pyrimidine ring is synthesized first then attached to ribose 5-phosphate in the form of PRPP
59
Thymidylate
(part of UTP)
- made when ribose is reduced to deoxyribose
- keeps thymine from being incorporated into RNA
60
Feedback inhibition of pyrimidine synthesis
- primary regulatory step is aspartate to N-carbamoylaspartate using aspartate transcarbamoylase
- end product CTP inhibits aspartate transcarbamoylase shutting down its own synthesis
61
Nucleoside monophosphate to nucleoside triphosphates
-adenylate kinase phosphorylates AMP to ADP
-ADP to ATP via glycolytic enzymes or by oxidative phosphorylation
-nucleoside monophosphate kinases
nucleoside diphosphate kinases
62
Nucleoside monophosphate kinases
- base specific
| - use ATP to phosphorylate
63
Nucleoside diphosphate kinases
- single enzyme
- not specific
- uses ATP to convert NDP to NTP
64
Ribonucleotide reductase
- catalyzes the reduction of the 2'-carbon of D-ribose to 2'-deoxyribose using ribonucleoside diphosphate substrates
- e- for this reduction come from NADPH either via glutathione and glutaredoxin or thioredoxin
65
Ribonucleotide reductase mechanism
- nucleoside diphosphate reduced by ribonucleotide reductase to form dNDPs via an active site radical which is stabilized by a binocular Fe3+ cofactor
- radical stabilize the cation after water loss
- 2 1-e- transfers with the oxidation of the dithiol reduces the radical cation
66
Regulation of ribonucleotide reductase
- primary regulation binding site
- substrate specificity site
* complex regulation
* just know that they are interconnected and keep a constant pool of all 4 deoxy and all 4 ribonucleotides
67
Primary regulation binding site
ATP binds and activates, dATP binds and inactivates
68
Substrate specificity site
ATP/dATP bind and favor reduction of UDP/CDP; dTTP binds and favors reduction of GDP; dGTP binds and favors reduction of ADP
69
Thymidylate (dTMP) derived from dCDP/dUMP
- de novo pathway of thymine only involves deoxyribonucleotides
- dUMP is the immediate precursor of dTMO and is catalyzed by thymidylate synthase which uses the cofactor THF to provide a methyl C at C5 of the uridine base
70
Purine and Pyrimidine degradation
- purines hydrolyzed to form free bases -> uric acid (allantoin in us)
- pyrimidines leads to ammonia production and urea synthesis
- carbon skeleton of thymine converted to succinyl-CoA
71
Gout
trouble breaking down nucleotides
| -uric acid build up in the joints
72
Purine and Pyrimidine salvage pathways
- free purine bases are released in cells during metabolic degradation and are salvaged by phosphoribosyltransferases which transfer the free purine base to PRPP
- simliar for pyrimidines have been identified in microorganisms, not identified in mammals
