BIOSYNTHESIS OF NUCLEOTIDES BIOSYNTHESIS OF NUCLEOTIDES PRESENTED BY PRACHEE RAJPUT (M.Sc ZOOLOGY, 1 ST SEM. ) DEPARTMENT OF ZOOLOGY & APPLIED AQUA- CULTURE BARKATULLAH UNIVERSITY, BHOPAL(M.P)
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BIOSYNTHESIS OFNUCLEOTIDES
BIOSYNTHESIS OF NUCLEOTIDES
PRESENTED
BY
PRACHEE RAJPUT (M.Sc ZOOLOGY, 1ST SEM. )
DEPARTMENT OF ZOOLOGY & APPLIED AQUA- CULTURE
BARKATULLAH UNIVERSITY, BHOPAL(M.P)
SYNOPSIS
INTRODUCTION DEFINITION BIOSYNTHESIS
(a) de-novo pathway(b) salvage pathway FUNCTION
CONCLUSION REFERENCES
INTRODUCTION
Nearly all organisms synthesize purines and pyrimidines de novo (“anew”).Many organisms also "salvage" purines and pyrimidines from diet and degradative pathways. Ribose generates energy, but purine and pyrimidine rings do not. Nucleotide synthesis pathways are good targets for anti-cancer/antibacterial strategies.
Nucleotides
RNA (ribonucleic acid) is a polymer of ribonucleotidesDNA (deoxyribonucleic acid) is a polymer of deoxyribonucleotidesBoth deoxy- and ribonucleotides contain Adenine, Guanine and Cytosine
Ribonucleotides contain UracilDeoxyribonucleotides contain Thym
Nitrogenous Bases
• Planar, aromatic, and heterocyclic• Derived from purine or pyrimidine• Numbering of bases is “unprimed”
Nucleic Acid Bases
Purines Pyrimidines
Sugars
• Pentoses (5-C sugars)• Numbering of sugars is “primed”
DEFINITIONNucleotides are the units of nucleic acids and composed of nitrogenous base,pentose sugar,and phosphate group.
These are the building blocks of nucleic acids (DNA and RNA).2. Involved in energy storage, muscle3. contraction,
active transport, maintenance of ion gradients
BIOSYNTHESISThere are two types of pathways lead to
nucleotides: de-novo pathways and the salvage pathways.
De-novo synthesis of nucleotides begins with their metabolic precursors: Amino acids,ribise-5-
phosphate,carbon dioxide and ammonia.Salvage pathways recycle the free bases and
nucleosides released from nucleic acid break down both types of pathways are important in cellular
metabolism.
Two major routes for nucleotide biosynthesis
dNTPs
dNTPs
Stryer Fig. 25.1
Purine Nucleotide Synthesis
OH
H
H
CH2
OH OH
H HO
O2-O3P
-D-Ribose-5-Phosphate (R5P)
O
H
H
CH2
OH OH
H HO
O2-O3P
5-Phosphoribosyl--pyrophosphate (PRPP)
P
O
O
O P
O
O
O
ATP
AMP
RibosePhosphatePyrophosphokinase
H
NH2
H
CH2
OH OH
H HO
O2-O3P
-5-Phosphoribosylamine (PRA)
AmidophosphoribosylTransferase
Glutamine + H2O
Glutamate + PPi
H
NH
H
CH2
OH OH
H HOO2-O3P
CO
H2C NH2
Glycinamide Ribotide (GAR)
GAR Synthetase
Glycine + ATP
ADP+ Pi
H2C
CNH
O
CH
HN
O
Ribose-5-Phosphate
Formylglycinamide ribotide (FGAR)
H2C
CNH
O
CH
HN
HN
Ribose-5-Phosphate
Formylglycinamidine ribotide (FGAM)
THFN10-Formyl-THF
GAR Transformylase
ATP +Glutamine +H2O
ADP +Glutamate + PiFGAM
Synthetase
HC
CN
CH
N
H2N
Ribose-5-Phosphate
4
5
5-Aminoimidazole Ribotide (AIR)
ATP
ADP + PiAIR Synthetase
C
CN
CH
N
H2N
OOC
Ribose-5-Phosphate
4
5
Carboxyamidoimidazole Ribotide (CAIR)
ATP+HCO3
ADP + PiAIR Car boxylase
Aspartate+ ATP
ADP+ Pi
SAICAR Synthetase
AdenylosuccinateLyase
Fumarate
C
CN
CH
N
NH
Ribose-5-Phosphate
4
5
5-Formaminoimidazole-4-carboxamideribotide (FAICAR)
CH2N
O
CH
O
C
CN
CH
N
H2N
Ribose-5-Phosphate
4
5
5-Aminoimidazole-4-carboxamideribotide (AICAR)
CH2N
O
C
CN
CH
N
H2N
CNH
O
HC
COO
CH2
COO
Ribose-5-Phosphate
4
5
5-Aminoimidazole-4-(N-succinylocarboxamide)ribotide (SAICAR)
THF
AICAR Transformylase
N10-Formyl-THF
Inosine Monophosphate (IMP)
HN
HCN
C
CC
N
CH
N
O
4
5
HH
CH2
OH OH
H HOO2-O3P
IMPCyclohydrolase
H2O
Purine Salvage Pathways
Nucleic acid turnover (synthesis and degradation) is an ongoing process in most cells.Salvage pathways collect hypoxanthine and guanine and recombine them with PRPP to form nucleotides in the HGPRT reaction. (Hypoxanthine-guanine phosphoribosyltranferase).In L-N, purine synthesis is increased 200-fold and uric acid is elevated in blood. This increase may be due to PRPP feed-forward activation of de novo pathways.
HGPRT Converts Bases Back to Nucleotides Using PRPP
Salvage pathways are very useful because of the high energy cost for denovo synthesis of nitrogen bases. The salvage pathway for adenine recovery(adenine phosphoribosyltranferase) is not shown.
Some Commonly Used Enzymes
• Nucleotidases cleave Pi from a nucleotide.• Nucleosidases cleave the base from a nucleoside. • Nucleoside phosphorylase cleaves the base from a
nucleoside using Pi. • Nucleoside kinase adds phosphate to a nucleoside.
N
NN
N
OCH2O - P -
NH2
OHHO
O
O
O
nucleoside phosphorylase
nucleotidase
nucleosidase_
_
O
Pi
2 ATP + HCO3- + Glutamine + H2O
CO
O PO3-2
NH2
Carbamoyl Phosphate
NH2
CNH
CH
CH2
C
COOO
HO
O
Carbamoyl Aspartate
HN
CNH
CH
CH2
C
COOO
O
Dihydroorotate
HN
CNH
C
CHC
COOO
O
Orotate
HN
CN
C
CHC
COOO
O
HH
CH2
OH OH
H HOO2-O3P
Orotidine-5'-monophosphate(OMP)
HN
CN
CH
CHC
O
O
HH
CH2
OH OH
H HOO2-O3P
Uridine Monophosphate(UMP)
2 ADP +Glutamate + Pi
CarbamoylPhosphateSynthetase II
AspartateTranscarbamoylase(ATCase)
Aspartate
Pi
H2O
Dihydroorotase
Quinone
ReducedQuinone
DihydroorotateDehydrogenase
PRPP PPi
Orotate PhosphoribosylTransferase
CO2
OMP Decarboxylase
Pyrimidine Synthesis
Pyrimidine SynthesisIn contrast to purines, pyrimidines are not
synthesized as nucleotides.Rather, the pyrimidine ring is completed before a
ribose-5-P is added.Carbamoyl-phosphate and aspartate are the
precursors of the six atoms of the pyrimidine ring.Mammals have two enzymes for carbamoyl
phosphate synthesis – carbamoyl phosphate for pyrimidine synthesis is formed by carbamoyl
phosphate synthetase II (CPS-II), a cyt
Biological functions of nucleotides
Building blocks of nucleic acids (DNA and RNA).2. Involved in energy storage, muscle contraction,
active transport, maintenance of ion gradients.3. Activated intermediates in biosynthesis
(e.g. UDP-glucose, S-adenosylmethionine).4. Components of coenzymes (NAD+, NADP+, FAD,
FMN, and CoA)5. Metabolic regulators:a. Second messengers (cAMP, cGMP)b. Phosphate donors in signal transduction (ATP) c. Regulation of some enzymes via adenylation and uridylylation
conclusion
From the above discussion it has been concluded nucleotides are the building blocks of RNA and DNA, This means that nucleotides act as a monomers units large no. of monomers units polymerize to form a polymer (‘RNA’ and ‘DNA’)RNA and DNA are the genetic material that inherits from one generation to other i.e. (parents to offsprings).
REFERENCES
LEHNINGER PRINCIPAL OF BIOCHEMISTRY BY NELSON AND COX
BIOCHEMISTRY BY SATYANARAYANA AND CHAKRAPANI
THANKS
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