METABOLISME ASAM NUKLEAT

Degradasi Nucleoprotein
Nucleoprotein

In Stomach Gastric acid and pepsin

Nucleic acid Protein

In small intestine Endonucleases: RNase and DNase

Nucleotide

Nucleotidase

Phosphate Nucleoside

Nucleosidase

Base Ribose
 PRODUK AKHIR PENCERNAAN ASAM NUKLEAT

Basa Nitrogen :
Purin and Pirimidin
Gula:
Ribosa and Deoksiribosa
Asam fosfor
 ABSORPSI
 Purin dan Pirimidin yang diperoleh dari
pencernaan asam nukleat diabsorpsi melalui usus
halus
Purin yg tidak terabsorpsi diekresikan melalui usus
besar dan feses
Basa nitrogen yang terabsorbsi dibawa ke hati dan
didegradasi
Ribosa diabsorpsi dan dikatabolisme menjadi
energi
 METABOLISME ASAM NUKLEAT

Anabolisme Asam Nukleat Katabolisme Asam Nukleat

Biosintesis Purin Degradasi Purin
Biosintesis Pirimidin Degradasi Pirimidin
SUMMARY OF PURINE
BIOSYNTHESIS
dADP dATP

AMP ADP ATP

IMP
GMP GDP GTP

dGDP dGTP
 ANTIMETABOLIT /INHIBITOR
PURIN NUKLEOTIDA

 Jalur biosintesis nukleotida merupakan target

anticancer/antibacterial strategies.
 Antimetabolit Purin nukleotida merupakan struktur analog
 Purine,
 Asam Amino
 Asam folat

 Senyawa antimetabolit ini dapat interfere, inhibit atau block jalur

biosintesis Purin nukleotida dan selanjutnya mem-blok sintesis DNA,RNA
dan protein.
Widely used to control cancer(Chemotherapeutic Agent).
 PURIN ANALOG
6-Mercaptopurine (6-MP) is a analog of
Hypoxanthine.

OH SH
N N
N N

N N N N
H H
hypoxanthine 6-MP
 6 MERCAPTA PURINE
6 Mercapta Purine adalah inhibitor
Enzim:
Adenyl Succinase
IMP Dehydrgenase
Menurunkan kadar AMP dan GMP
 Folat analogs

 Methotrexate and Sulfonamides block Purine

biosynthesis

Sulfonamides structural analogs of PABA inhibits

Folate Synthesis in microbes. It indirectly inhibit
Purine biosynthesis
 FOLIC ACID ANALOGS

Aminopterin (AP) and Methotrexate (MTX)

NH2 R O COOH
N
N CH2 N C NH C CH2 CH2 COOH
H
H2N N N
R＝H：AP R＝CH3：TXT
MTX

OH H O COOH
N
N CH2 N C NH C CH2 CH2 COOH
H
H2N N N
folic acid
 ANTI CANCER DRUGS: METHOTREXATE
Methotrexate, one of the earliest anti-cancer drugs,
inhibits folate metabolism
Folate provides methyl groups for biosynthetic
reactions
It is essential for the conversion of dUMP to TMP
It provides carbon for the purine ring.
Sulfonamides are effective anti-
bacterial agents
Methotrexate and Aminopterin are
folic acid analogs that have been
used in cancer chemotherapy
SUMMARY OF PYRIMIDINE
BIOSYNTHESIS
dTMP dTDP dTTP

dUMP dUDP

UMP UDP UTP

CDP CTP

dCMP dCDP dCTP

Antimetabolites of Pyrimidine nucleotides are similar with
them of Purine nucleotides.
5-fluorouracil (5-FU) is a analog of Thymine

O O
F CH3
HN HN

O N O N
H H

5-FU thymine
5-fluorouracil
(5-FU) is used as a
chemotherapeutic
agent in the
treatment of
cancers

5-fluorocytosine is
used as an
antifungal drug

5-fluoroorotate is an
effective
antimalarial drug
The 5-Fluoro substitution
inhibits on the mechanism
of action of Thymidylate
Synthase.
Which in turn affects DNA
synthesis.
 DEGRADASI PURINE

Produk akhir katabolisme purin : asam urat

Asam urat atau gout adalah
gangguan yang dipicu oleh tingginya
kadar asam urat.
2, 6,8 TRI OXY PURINE
 Asam urat merupakan hasil akhir
metabolisme purin (nucleoprotein).
Purin berasal dari makanan dan hasil
sintesis dari CO2, glutamine, glisin,
asam folat.
Asam urat merupakan sampah hasil
metabolisme normal dari pencernaan
makanan yang mengandung purin
atau dari penguraian purin (sel tubuh
yang rusak).
Treatment: Allopurinol – Competitive
Inhibitor of Xanthine Oxidase
Allopurinol – inhibitor used to treat Gout

O O
C C H
N C
HN C HN C
CH N
HC C HC C
N N N
N H H
Hypoxanthine Allopurinol

Xanthine oxidase

Xanthine oxidase
DEGRADASI PIRIMIDIN