Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Biochemistry Renal > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

(51 cards)

Start Studying
1
Q

Which nucleotides have a double ring structure

A

Purines (A, G)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Nucleoside =

A

Base and the pentose sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nucleotide de novo synthesis precursors

A

Amino acids

Ribose-5P

CO2

NH3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the same between purine and pyrimidine synthesis?

A

Multienzyme complex

Common precursor = phosphoribosyl pyrophosphate (PRPP)

Use ribose as the sugar

Glutamine and aspartate are the source for amino groups for the purine and pyrimidine rings

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Differences between purine and pyrimidine synthesis

A

Glycine contributes to the purine ring only

Pyrimidine base is 1st made…and then attached to the ribose sugar (as part of PRPP)

Where…purine bases are made already associated with PRPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

PRPP synthetase

A

PRPP = common intermediate for both purine and pyrimidine synthesis

Phosphorylates ribose-5P with a pyrophosphate molecule derived from ATP

important regulated step in boht de novo pathways…

Activated by inorganic phosphate

Feedback inhibited by purine nucleotides

PRPP is also involved in salvage pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

From what is ribose5P produced from?

A

Glucose (PPP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Carbon sources in the purine ring

A

CO2 and formate

Formate donated from N-formyl H4folate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Nitrogen contribution in the purine ring?

A

From glutamine and aspartate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Glycine contribution to the purine ring

A

Carbon and nitrogen atoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Purinosome

A

Multienzyme complex

10 reactions to make purines (after PRPP synthesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Glutamine PRPP amidotransferase

A

1st reaction in purinosome

Condenses the NH3 from glutamine to the C1 atom of PRPP

Product: 5’-phosphribosylamine

Liberating….PPi and glutamate

This is the beginning of the making of the purine ring attached to the ribose sugar

Commitment step and 2nd regulated step

Activated by PRPP

Feedback inhibited by endproducts of the later reacrtions, AMP, GMP, and IMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Important cofactor in 2 steps of the purinosome overall reaction

A

H4Folate to supply the formyl groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Sulfonamide drugs

A

Structural analogs that inhibit bacterial synthesis of folic acid…as such

They inhibit purine synthesis in bacteria

  • humans do not make folate, must be obtained in diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Methotrexate

A

Folic acid analog

Inhibit the regeneration (reduction) of H2Folate —> H4Folate

Inhibits purine synthesis in cancer cells, but are also toxic to all dividing cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Final product of the purine de novo synthesis

A

Inosine5-monoPhosphate (IMP)

Nitrogenous base = hypoxanthine

2 additional reactions are needed to convert IMP to either AMP or GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

AMP generation from IMP

A

Additions of aspartate to the inosine ring structure

Enzyme: adenylosuccinate synthetase

Fumarate is then removed in the next reaction…leaving the alpha amino group from aspartate in place

This replaces the C5 keto group with an amino group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

GMP generation from IMP

A

Oxidation of the purine ring…making a C7 keto group

IMP dehydrogenase

An amino group donated from glutamine replaces the keto group to form GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

AMP and GMP synthesis regulation

A

End products feedback inhibit the 1 st reactions in their synthesis

AMP production requires hydrolysis of GTP

While GMP needs ATP hydrolysis

So….

If [AMP] high…so is [ATP]…this will stimulate GMP production…evening the concentrations of AMP and GMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Mycophrenolic acid

A

Reversible inhibitor of IMP dehydrogenase

Drug depletes purines in the T and B lymphocytes

Used as an immunosuppressant to prevent graft rejections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

5’-nucleotidase

Study These Flashcards
A

Removes the phosphate groups to generate a nucleoside in IMP, AMP, GMP degradation

1st reaction

22
Q

Purine nucleoside phosphorylase

Study These Flashcards
A

2nd reaction in IMP, AMP, GMP degradation

Removes ribose sugar (as ribose-1P) to generate the free nitrogenous base

23
Q

What base does the degradation of IMP and AMP converge on?

Study These Flashcards
A

Hypoxanthine

Both deaminated to inosine…which is then converted to hypoxanthine

24
Q

Xanthine oxidase

Study These Flashcards
A

Oxidizes hypoxanthine —> xanthine

IMP and AMP degradation

The GMP is also degradated down to xanthine…

So all 3 converge on the base xanthine

25
Xanthine —> uric acid
Also done by xanthine oxidase Uric acid is readily excreted in the urine
26
Gout
High blood levels of uric acid (hyperuricemia) = the end product of purine catabolism Either the overproduction or under excretion of uric acid Leads to deposition of urate crystals in the joints —> inflammatory response Diagnosis requires examination of synovial fluid Majority of the time due to lack of excretion of uric acid...can be due to processees that affect how the kidney handles urate (i.e. lactate competes for same channels that allow urate excretion) Thiazide diuretics or exposure to lead can also affect urate excretion, leading to saturnine gout
27
Primary hyperuricemia
Less common cause of gout (overproduction of uric acid) Possible X-linked PRPP synthetase mutation Results in increase Vmax for the production of PRPP, a lower Km for ribose-5P or decreased sensitivity to purine nucleotides...its allosteric inhibitor
28
Probenecid or sulfinpyrazone
Increase renal excretion of uric acid
29
Allopurinol
Lowers uric acid snythesis Its converted in the body to oxypurinol, a suicide inhibitor of xanthine oxidase Reulsts in an accumulation of hypoxanthine and xanthine —> compounds more soluble than uric acid
30
Adenosine daminase (ADA)
Enzyme that deaminates adenosine —> inosine Expressed in cytosol of all cells Humans - lymphocytes have highest activity
31
ADA deficiency
Accumulation of adenosine Which is converted to its ribonucleotide or deoxyNT forms by cellular kinases As dATP levels rise...riboNT reductase is inhibited Which reduced ribose sugar —> 2’-deoxyribose So... cells cannot make DNA and divide
32
Severe Combined Immunodeficiency Disease
Can be caused by a severe ADA deficiency Decrease in T and B cells since cannot divide, make DNA
33
Purine nucleoside phosphorylase deficiency
Autosomal recessive Like ADA deficiency also causes immunodeficiency Less severe and only affects T cells....prompting an increase in infections
34
Enzymes involved in the purine salvage pathway
Adenine phosphoribosyltransferase (APRT) Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) Both condense the free nitrogenous base and PRPP....to form AMP, IMP, or GMP The release of the pyrophosphate and its subsequent hydrolysis make these reactions irreversible
35
Lesch-Nyhan syndrome
X-linked, recessive (-) HGPRT Results in inability to salvage hypoxanthine or guanine Leads to excessive degradation and uric acid levels Also causes increase PRPP and decreased IMP and GMP....therefore the glutamine PRPP amidotransferase (purine syn. Commitment step) is unregulated Purine synthesis is increased...adds to increased degradation and increase uric acid Uric acid stones in kidneys, urate crystals, motor dysfunction, cognitivie defects...self mutilation Allopurinol = effective treatment ... but not for mental shit
36
Unlike the purine ring...the pyrimidine ring
Is made before being attached to the ribose-5P Which is then donated by PRPP
37
Sources of the atoms in the pyrimidine ring
Glutamine, CO2, and aspartic acid
38
Pyrimidine synthesis
Begins with the condensation of CO2 and an amino group from glutamine to form Carbamoyl phosphate Enzyme: carbamoyl phosphate synthetase II (CPSII) ....which is the isoform of the CPS1 enzyme that starts the urea cycle in mitochondria
39
The regulated step in pyrimidine synthesis
CPS II reaction Feedback inhibited by UTP (end product) Activated by the substrates ATP, PRPP
40
Second step of pyrimidine synthesis
Aspartate transcarbamoylase Carbamoyl phosphate —> carbamoylaspartate
41
Dihydroorotase
3rd enzyme in pyrimidine synthesis Closes the pyrimidine ring The resulting dihydroorotate is oxidixed to produce orotic acid
42
Dihydroorotate dehydrogenase
Inner mitochondrial membrane Produces ortate (orotic acid) from dihyrdroorate Pyrimidine synthesis **all other enzymes in this pathway are cytosolic
43
Orotate phosphoribosyl transferase
Produces OMP from the complete pyrimidine ring...and releases the pyrophosphate PRPP is the ribose-5P donor Irreversible
44
Orotidylate decarboxylase
OMP —> UMP Removes the acidic carboxyl group UMP is then phosphorylated to UDP and UTP
45
UMP synthase
Catalytic domains = 1. Orotate phosphoribosyl transferase = makes OMP 2. Orotidylate decarboxylate = makes UMP from OMP
46
Orotic aciduria
Deficiency in the UMP synthase Orotic acid in the urine Poor growth Megaloblastic anemia Treated with uridine which is phosphorylated to UTP...thereby inhibiting the CPSII and decreasing orotate levels
47
Pyrimidine synthesis regulation
CPSII = key regulated step (like the PRPP synthetase in purine synthesis) Inihibited by UTP Activated by PRPP
48
RiboNT reductase
How dNTs are made from ribo diphosphates (ADP, GDP, UDP, etc) Reduces the 2’OH group of the riboDPs to hydrogen Enzyme now has a disulfide bond (oxidized) Thioredoxin reduces the enzyme back to the active form (NADPH) Inhibited by dATP...binds to allosteric sites —> why high dATP levels are toxic in ADA deficiency ATP activates the enzyme
49
Hydroxyurea
Destroys the free radical required for the enzyme activity of riboNT reductase Thus inhibits the generation of dNTs Used to treat cancers, such as chronic myelogenous leukemia Also treats sickle cell disease
50
Formation of deoxyThymidine
.dUDP and dCDP are phosphorylated to dCTP and dUTP... These are converted to dUMP..which is the substrate for thymidylate synthase To make dTMP Adds a methyl group to the C5 atom of the uracil ring to form thymine (H4folate cofactor) Dihydrofolate reductase and serine hydroxymethyl transferase regenerate H4folate from H2folate afterwards Inhibited by thymine analogs such as 5-fluorouracil (5-FU) - antitumor agent
51
Folate deficiency
Folate is not stored in the body to any large degree So need diet supply Need to maintain function of cofactors such as H4Folate Results in decrease availability of deoxyThymidine...affects DNA synthesis and repair Associated with macrocytic anemia (large RBCs)

Biochemistry Renal (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions