building blocks nucleic acids purines and pyrimidine metabolism

what is the difference between nucleotide and nucleoside

nucleotides contain a phosphate

what are the shared components of nucleotides and nucleosides

1. pentose sugar

2. 5 types of nitrogenous bases

what is the pathway that forms an intermidate metabolite ribose-5 phosphate

pentose phosphate shunt/hexose monophosphate HMP shunt

where is ribose found

RNA

where is deoxyribose found

DNA

which carbon is considered the 1° carbon

the carbon containing the nitrogenous base

what is 1

what is 2

what is 3

what is 4

what is 5

how many rings does purine contain

2

how many rings does pyrimidine contain

1

what bases are purine

• adenine

• guanine

what bases are pyrimidine

• cytosine

• thymine

• uracil

what bases does DNA contain

a

g

c

t

what bases does RNA contain

A
G
C
U

what nucleosides are associated with adenine

adenosine

deoxyadenosine

what nucleotides are associated with adenine

AMP

dAMP

ADP

dADP

ATP

dATP

what nucleosides are associated with guanina

Guanosine

deoxyguanosine

what nucleotides are associated with guanine

GMP

GDP

GTP

what nucleosides are associated with cytosine

cytidine

what nucleotides are associated with cytosine

CMP
CDP
CTP

what nucleosides are associated with uracil

uridine

what nucleotides are associated with uracil

UMP
UDP
UTP

what nucleosides are associated with thymine

thymidine

what nucleotides are associated with thymine

dTMP

dTDP

dTTP

what are the functions of nucleotides

• building blocks

• source of energy

• signal molecules

• activators for transfer of groups

• regulators

• carrier molecules

what is the goal of de novo purine synthesis

create AMP and GMP

what are the ingredients for de novo purine synthesis

ribose 5 phosphate

whats the nitrogen source for de novo purine synthesis

amino acids

• glycine

• aspartate

• glutamate

what is the carbon source for de novo purine synthesis

tetrahydrofolate THF

CO2

what is PRPP synthetase stimulated by

intracellular phosphate

what is PRPP synthase inhibited by

AMP

IMP

GMP

what is PRPP glutamyl amidotransferase stimulated by

PRPP

what is PRPP glutamyl amidotransferase inhibited by

AMP
IMP
GMP

what is adenylosuccinate synthase inhibited by

AMP

what is IMP dehydrogenase inhibited by

GMP

what are the inhibitors of purine synthesis

6-mercaptopurine (6-MP) and its prodrug azathioprine

mycophenolate

what does 6-MP inhibit specifically

PRPP to IMP

what does mycophenolate inhibit specifically

IMP dehydrogenase

what is purine salvage pathway

recycled purine bases + PRPP → PPI + purine mono nucletides (AMP, GMP, IMP)

what enzymes are associated with purine salvage pathway

1. adenine phosphoribosyltransferase (APRT)

2. hypoxanthine guanine phosphoribosyltransferase (HGPRT)

what is the product of purine salvage pathway

• AMP

• GMP

• IMP

what does a dificiency of HGPRT lead to

Lesch-Nyhan syndrome

what is purine metabolized into

uric acid

what is purine excreted in

urine as urate anion

what are the steps in AMP degredation

AMP → adenosine → inosine → hypozanthine → xanthine → uric acid

what is the location of deoxyribonucleotide synthesis

all tissues

what are the steps in GMP degradation

GMP → guanosine → guanine → xanthine → uric acid

what substrates are associated with the synthesis of deoxyribonucleotides

• ADP

• CDP

• UDP

• NADPH

***must be diphosphates

what are the products of deoxyribonucleotide synthesis

• dADP

• dCDP

• dUDP

• dGDP

what does ribonucleotide reductase act to do?

reduce the ribonucleotide to deoxyribonucleotide

what provides the reducing power for the ribonucleotide reductase

two sulfhydryl froups

what is oxidized in the process of the synthesis of deoxyribonucleotide

thioredoxin

what does thioredoxin reductase require to convert the oxudized state of thioredoxin back to the reduced state

NADPH

what is the goal of de novo pyrimidine synthesis

create UMP

what is the nitrogen source of de novo synthesis

carbamoyl phosphate

what is the nitrogen source for de novo pyrimidine synthesis

amino acids (aspartate and glutamine)

what is the carbon source for de novo pyrimidine synthesis

tetrahydrofolate THF

CO2

where is CPS 2 present in

cytosol

where is CPS 2 used

pyrimidine synthesis

what is the nitrogen source for CPS 2

glutamine

how is CPS 2 activated

PRPP

how is CPS 2 inhibited

UTP

where is CPS 1 present

mitochondria

where is CPS 1 used

urea cycle

what is the nitrogen source for CPS 1

ammonia

how is CPS 1 activated

N-acetyl glutamate

is adenine and guanine a purine or pyrimidine

pureine

is cytosine, thymine, and uracil a purine or pyrimidine

pyrimidine

what base pair melts/ breaks apart at lower temps and why?

AT bonds because they only share 2 H-bonds.

what two things added together composes a nucleoside

base and sugar

what two things added together gives you a nucleotide

nucleoside and phosphate group

what is the sequence of purine synthesis pathway

ribose 5-P → PRPP → IMP → AMP or GMP

what is the first purine nucleotide formed in the purine synethesis pathway?

IMP

which drug inhibits the enzyme IMP dehydrogenase thereby blocking GMP synthesis?

Mycophenolate

what does hypoxanthine and PRPP combined result in

IMP

what does guanine and PRPP combined result in

GMP

what does adenine and PRPP combined result in

AMP

what is HGPRT inhibitedd by

IMP and GMP

what does a deficency in HGPRT result in

Lesch-Nyhan syndrome

what are the clinical features of lesch-nyhan syndrome

• high uric acid levels

• congenitive issues and delayed development

• muscle movement problems (dystonia and chorea)

• agressive behavioir, self harm

• gouty arthritis

is lesch nyhan syndrome x linked recessive or x linked dominant

x linked recessive

what enzyme does lesch nyhan syndrome lack

HGPRT enzyme

what causes high uric acid in lesch nyhan syndrome

the inability to recycle guanine and hypoxanthine

what causes extra purine production in lesch nyhan syndrome

more PRPP and less IMP and GMP

what are the clinical importance of hyperuricemia

Overproduction or underexcretion of uric acid → hyperuricemia → gout

what are the risk factors of hyperuricemia

High-protein, high-fat diet, fructose, alcohol

what are the clinical features of hyperuricemia

Joint urate crystal deposition → Monoarticular arthritis, tophi, kidney stones

what are the treatment options for hyperuricemia

Allopurinol/febuxostat inhibit xanthine oxidase, increase soluble compounds

what does HCO3 + glutamine + 2ATP result in

carbamoyl phosphate

what does carbamoyl aspartate result in

orotate

what does orotate + PRPP result in

UMP

what does UMP + ATP result in

UDP

what does UDP + ATP result in

UTP

what does UTP + glutamine + ATP result in

CTP

what enzyme is missing in hereditary orotic aciduria

UMP

what are the symptoms of hereditary orotic aciduria

• stunted growth

• orotic acid crystals in urine

• mmegaloblastic anemia