Chapter 13 - Nucleotide Metabolism

What are the three main components of nucleotides?

Pentose sugar

Phosphate group

Nitrogen-containing base

What carbon does the phosphate group attach to?

5’ carbon of the pentose

What carbon does the nitrogen-containing base attach to?

1’ carbon of the pentose

What are the purines?

Adenine and guanine

What are the pyrimidines?

Cytosine, uracil, thymine

What is the difference between ribonucleotides and deoxyribonucleotides?

Ribose - OH on 2’ carbon

Deoxyribose - H on 2’ carbon

In what pathway are the sugar phosphates produced?

Pentose phosphate pathway

How are sugar phosphates activated?

Pyrophosphate (2 phosphates) added to C-1

What enzyme is involved in activating sugar phosphates?

PRPP synthetase

When synthesizing purines de novo, how is the ring constructed?

Bit by bit directly on the activated R-5-P

What is the parent compound for purines?

Inosine monophosphate (IMP)

What nutrient is required to synthesize purines?

Folate (B9)

How does the salvage pathway produce ‘new’ purines?

Adds recycled purine bases and adds to activated R-5-P (PRPP)

What is the disease associated with a faulty HGPRT enzyme?

Lesch-Nyhan Syndrome

What is the result of a faulty HGPRT enzyme?

Prevent recycled purines from being used in the salvage pathway.

What is needed to convert IMP to AMP?

Aspartate and GMP

What is needed to convert IMP to GMP?

Glutamine and ATP

What additional coenzyme does production of G require?

NADH + H

What is the enzyme involved in the committed step of purine synthesis?

GPAT

What stimulates GPAT?

increased PRPP levels (increased substrate)

What inhibits GPAT?

increased AMP and/or GMP levels (increased product)

What are the ring donors for purine synthesis?

Aspartate

Glutamine 2x

Glycine

THF 2x

CO₂

How is the pyrimidine ring constructed?

Produced first, then added to activated R-5-P

What is the parent compound for pyrimidine synthesis?

Uridine monophosphate - UMP

What is needed to convert UMP to CTP?

Glutamine

What is needed to convert UMP to dTMP?

THF and B9

What enzyme is required to convert UMP to dTMP?

Thymidylate synthase

What are the coenzymes required for pyrimidine production?

B9 (T only)

ATP

FMN

NAPH (T only)

What specific coenzymes are only required to produce T?

B9 and NAPH

What enzyme is involved in the committed step of pyrimidine synthesis?

CPS II

How is CPS II stimulated?

Increased levels of PRPP

How is CPS inhibited?

Increased levels of UTP

What are the ring donors for pyrimidine synthesis?

Aspartate

Glutamine

HCO₃^-

What enzyme makes deoxyribonucleotides from ribonucleotides?

Ribonucleotide reductase

What form must nucleotides be to use ribonucleotide reductase enzyme?

Diphosphate

What enzyme converts GMP to GDP?

Guanylate kinase

What enzyme converts GDP to GTP?

Nucleoside diphosphate kinase

What enzyme removes the Pi from GMP?

5’ nucleotidase

What enzyme removes the sugar from guanosine?

Converts guanosine to guanine.

Nucleosidase

What enzyme removes the amino group from guanine?

Guanine to xanthine

Guanine deaminase

What enzyme converts xanthine to uric acid?

Xanthine oxidase

What enzyme converts adenosine to inosine?

Removes the amino group

Adenosine deaminase

What enzyme converts inosine to hypoxanthine?

Nucleosidase

What enzyme converts hypoxanthine to xanthine?

Xanthine oxidase

What is the final product of GMP and AMP degradation?

Uric acid

What disease is characterized by a buildup of uric acid?

Gout

What disease is characterized by a deficiency in the ADA (adenosine deaminase) enzyme?

SCID

The increase in activity of what enzyme can lead to gout?

Xanthine oxidase

What is the breakdown product of cytosine and uracil?

Beta-alanine

What is the breakdown product of thymine?

Beta-aminoisobutyrate

What is the fate of beta-aminoisobutyrate, produced by the breakdown of T?

Excrete or go to Krebs cycle