ANFS475: Nucleotide Metabolism

Nucleotides and Energy

not an energy source, requires a lot of energy to form and break down

Nucleotide Function

critical genetic information

Pentose Phosphate Pathway

metabolic process connected to glycolysis, ribose 5 phosphate production for nucleotide biosynthesis

Nucleotides and Nitrogen

contains many nitrogen, free ammonia produced with break down

Nucleic Acid Components

base, sugar, phosphodiester linkage

Nucleotide Base

purine or pyrimidine nitrogenous base

Nucleotide Base Examples

adenine, guanine, cytosine, thymine, uracil

Purine Bases

adenine, guanine, double ringed

Pyrimidine Bases

cytosine, thymine, uracil, single ringed

Nucleotide Base Pairing

adenine to thymine, cytosine to guanine

Nucleoside

two components, base and sugar

Nucleotide

three components, base, sugar, phosphate

Adenine Nucleoside

adenosine

Adenine Nucleotide

adenylic acid, adenosine monophosphate (AMP)

Guanine Nucleoside

guanosine

Guanine Nucleotide

guanylic acid, guanosine monophosphate, GMP

Cytosine Nucleoside

cytidine

Cytosine Nucleotide

cytidylic acid, cytidine monophosphate, CMP

Uracil Nucleoside

uridine

Uracil Nucleotide

uridylic acid, uridine monophosphate, UMP

Thymine Nucleoside

deoxythymidine

Thymine Nucleotide

deoxythymidylic acid, deoxythymidine monophosphate, dTMP

Uric Acid

purine ribonucleotide breakdown product

Purine Base Structure

C5 N4, synthesized from many compounds

Purine Nitrogen 1 Origin

aspartate amine

Purine Carbon 2 Origin

formate

Purine Nitrogen 3 Origin

glutamine amide

Purine Carbon 4 Origin

glycine

Purine Carbon 5 Origin

glycine

Purine Carbon 6 Origin

bicarbonate, HCO3-

Purine Nitrogen 7 Origin

glycine

Purine Carbon 8 Origin

formate

Purine Nitrogen 9 Origin

glutamine amide

Inosine Monophosphate (IMP)

purine precursor for adenine and guanine

IMP Biosynthesis Reaction 1

ribose 5 phosphate to PRPP

IMP Biosynthesis Reaction 1 Enzyme

ribose phosphate pyrophosphokinase

IMP Biosynthesis Reaction 1 Description

ATP to AMP

IMP Biosynthesis Reaction 2

PRPP to PRA

IMP Biosynthesis Reaction 2 Enzyme

amidophosphoribosyl transferase

IMP Biosynthesis Reaction 2 Description

glutamine and water in, glutamate and PPi out

IMP Biosynthesis Reaction 3

PRA to GAR

IMP Biosynthesis Reaction 3 Enzyme

GAR synthetase

IMP Biosynthesis Reaction 3 Description

glycine and ATP in, ADP and Pi out

IMP Biosynthesis Reaction 4

GAR to FGAR

IMP Biosynthesis Reaction 4 Enzyme

GAR transformylase

IMP Biosynthesis Reaction 4 Description

N10 formyl THF in, THF out

IMP Biosynthesis Reaction 5

FGAR to FGAM

IMP Biosynthesis Reaction 5 Enzyme

FGAM synthetase

IMP Biosynthesis Reaction 5 Description

ATP and glutamine and water in, ADP and glutamate and Pi out

IMP Biosynthesis Reaction 6

FGAM to AIR

IMP Biosynthesis Reaction 6 Enzyme

AIR synthetase

IMP Biosynthesis Reaction 6 Description

ATP to ADP and Pi

IMP Biosynthesis Reaction 7

AIR to CAIR

IMP Biosynthesis Reaction 7 Enzyme

AIR carboxylase

IMP Biosynthesis Reaction 7 Description

ATP and bicarbonate in, ADP and Pi out

IMP Biosynthesis Reaction 8

CAIR to SAICAR

IMP Biosynthesis Reaction 8 Enzyme

SAICAIR synthetase

IMP Biosynthesis Reaction 8 Description

aspartate and ATP in, ADP and Pi out

IMP Biosynthesis Reaction 9

SAICAR to AICAR

IMP Biosynthesis Reaction 9 Enzyme

adenylosuccinate lyase

IMP Biosynthesis Reaction 9 Description

fumarate out

IMP Biosynthesis Reaction 10

AICAR to FAICAR

IMP Biosynthesis Reaction 10 Enzyme

AICAR transformylase

IMP Biosynthesis Reaction 10 Description

N10 formyl THF in, THF out

IMP Biosynthesis Reaction 11

FAICAR to IMP

IMP Biosynthesis Reaction 11 Enzyme

IMP cyclohydrase

IMP Biosynthesis Reaction 11 Description

water out

AMP Synthesis Reaction 1

IMP to adenylosuccinate

AMP Synthesis Reaction 1 Enzyme

adenylosuccinate synthetase

AMP Synthesis Reaction 1 Description

aspartate and GTP in, GDP and Pi out

AMP Synthesis Reaction 2

adenylosuccinate to AMP

AMP Synthesis Reaction 2 Enzyme

adenylosuccinate lyase

AMP Synthesis Reaction 2 Description

fumarate out

GMP Synthesis Reaction 1

IMP to XMP

GMP Synthesis Reaction 1 Enzyme

IMP dehydrogenase

GMP Synthesis Reaction 1 Description

produces NADH

GMP Synthesis Reaction 2

XMP to GMP

GMP Synthesis Reaction 2 Enzyme

GMP synthetase

GMP Synthesis Reaction 2 Description

glutamine and ATP and water in, glutamate and AMP and PPi out

Mycophenolic Acid

immunosuppressant that inhibits IMP dehydrogenase, blocking GMP production

Purine Biosynthesis Activation

PRPP is only activator, from pentose phosphate pathway action

AMP, ADP, ATP Feedback

inhibits amidophosphoribosyl transferase action, PRPP to PRA

ADP Feedback

inhibits ribose phosphate pyrophosphokinase action, R5P to PRPP

AMP Feedback

inhibits adenylosuccinate synthetase action, IMP to adenylosuccinate

GMP, GDP, GTP Feedback

inhibits amidophosphoribosyl transferase action, PRPP to PRA

GDP Feedback

inhibits ribose phosphate pyrophosphokinase action, R5P to PRPP

GMP Feedback

inhibits IMP dehydrogenase action, IMP to XMP

XMP Feedback

inhibits amidophosphoribosyl transferase action, PRPP to PRA

Salvage Reactions

convert purines to nucleotide forms

Pyrimidine Molecular Origins

glutamine amide, aspartate, bicarbonate

Pyrimidine Nitrogen 1 Origin

aspartate

Pyrimidine Carbon 2 Origin

bicarbonate, HCO3-

Pyrimidine Nitrogen 3 Origin

glutamine amide

Pyrimidine Carbon 4 Origin

aspartate

Pyrimidine Carbon 5 Origin

aspartate

Pyrimidine Carbon 6 Origin

aspartate

UMP Synthesis Reaction 1

glutamine and bicarbonate to carbamoyl phosphate

UMP Synthesis Reaction 1 Enzyme

carbamoyl phosphate synthetase II

UMP Synthesis Reaction 1 Description

2 ATP and water in, 2 ADP and glutamate and Pi out

UMP Synthesis Reaction 2

carbamoyl phosphate to carbamoyl aspartate