Nucleotide metabolism

Question 1

Nucleosides vs nucleotides

Answer 1

nucleotides are phosphate esters of nucleosides meaning nucleotide = base + sugar + phosphate
nucleoside = base + sugar

nucleotides form together to become polynucleotides = nucleic acids = DNA/RNA

Question 2

Structure of ATP

Answer 2

adenine = base
ribose = sugar
triphosphate

Question 3

purines

Answer 3

this is the two ring base (big ring, small name)
A, G
inosine (I)
xanthosine (X)

Question 4

pyrimidines

Answer 4

this is the one ring base (small ring, big name)

C, U, T

Question 5

phases of purine nucleotide synthesis and their products

Answer 5

1) ribose 5-phosphate activation: PRPP
2) convert PRPP to PRA: PRA
3) construct IMP ring: IMP
4) convert IMP to adenosine and guanosine (deoxy)nucleotides: ATP/dATP or GTP/dGTP

Question 6

methotrexate disorders

Answer 6

methotrexate is structurally very similar to folic acid. It can act as a competitive inhibitor of enzymes that utilize folate bc the structures are so similar. This inhibits DNA replication

Question 7

three phases of pyrimidine synthesis and their products

Answer 7

1) fabrication of orotate ring: orotate
2) attach PRPP to orotate ring: UMP
3) convert UMP to UDP: UDP can be converted to UTP/dUTP, CTP/dCTP, TTP/dTTP

Question 8

three phases of pyrimidine synthesis and their products

Answer 8

1) fabrication of orotate ring: orotate ring
2) attach PRPP to orotate ring: UMP
3) convert UMP to UDP: UDP can be converted to UTP/dUTP, CTP/dCTP, TTP/dTTP

Question 9

regulatory points of pyrimidine biosynthesis

Answer 9

prior to the creation of carbamoyl phosphate CARBAMOYL PHOSPHATE SYNTHETASE is inhibited by UMP (feedback inhibition)

ATCase is inhibited by CTP

Question 10

5-fluorouracil

Answer 10

Adrucil is an anti cancer drug that blocks the production of thymidylate synthase (creates dTTP/TTP) and therefore would prevent DNA production.

Question 11

Acyclovir

Answer 11

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used in the breakdown of thymine into dTMP.

Question 12

enzymes responsible for nucleotide degradation

Answer 12

ribonucleases and deoxyribonucleases: chopping down RNA and DNA into oligomers

phosphodiesterases: converts short chain oligomers to NMPs or dNMPs
nucleotidases: converts the NMP/dNMP into nucleosides/deoxynucleosides
nucleosidases: removes the ribose/sugar from the nucleosides into pyrimidines and purines

Question 13

purine catabolism (break-down)

Answer 13

GMP follows nucleotide degradation until guanine is free. Guanine is converted into xanthine by removing an amine group and adding O2 (leads to uric acid). IMP or AMP are converted to Inosine (AMP –> to adenosine).

The important understanding of this pathway is that three oxygens are added to the purines until uric acid is created. Build of uric acid = gout. the more oxygen the less soluble = stones

Question 14

xanthine oxidase

Answer 14

enzyme used to convert xanthine to uric acid. This is inhibited if a patient has gout to limit the buildup of uric acid.

Question 15

gout

Answer 15

inflammation, swelling and pain associated with joints due to a build up of uric acid crystals in the joint spaces. from protein-rich food/wine.

Question 16

pyrimidine catabolism

Answer 16

UDP/CDP/TDP (and their deoxy forms) are catabolized into water soluble malonyl CoA (kentogenic pathway, goes into fatty acid synthesis) and methylmalonyl CoA/succinyl CoA (glucogenic, into TCA pathway).