MET ABOLISM:
Str uctur e and Metabolism of Nucleotide
USMAN SUMO FRIEND T AMBUNAN ARL I ADIT YA PARIKESIT
Nucleotide Function
Building blocks for DNA and RNA
Intr acellular sour ce of ener gy - Adenosine tr iphosphate (AT P)
Second messenger s - Involved in intr acellular signaling (e.g. cy clic adenosine monophosphate [cAMP])
Str uctur e of a Nucleotide
Despite the complex ity and diver sity of life the str uctur e of DNA is dependent on only 4 differ ent nucleotides
Diver sity is dependent on the nucleotide sequence
All nucleotides ar e 2 r ing str uctur es composed of:
5-carbon sugar : -D-ribose (RNA)
-D-deoxyribose (DNA)
Base Purine
Pyrimidine
Str uctur e of a Nucleotide:
Sugar
A Pentose sugar
T his is a 5 car bon sugar
Str uctur e of a Nucleotide:
Bases - Purines
Nucleotide Str uctur e - 2
Bases - Py r imidines
Nucleotide Str uctur e:
Bases - Py r imidines
Phosphate Gr oups
• Phosphate gr oups ar e what makes a nucleoside a nucleotide
• Phosphate gr oups ar e essential for nucleotide poly mer ization
P O
O
O
O X
Number of phosphate gr oups deter mines nomenclatur e
Phosphate Gr oups
P
2-Nucleotide
Sugar Phosphate “backbone”
Nucleic Acid
Str uctur e
Nucleic Acid Str uctur e:
“
Base Pair ing
”
• RNA [nor mally ] ex ists as a single str anded
poly mer
• DNA ex ists as a double str anded poly mer
• DNA double str and is cr eated by hy dr ogen
bonds between nucleotides
• Nucleotides alway s bind to complementar y
nucleotides
A
T
C
G
(2 H-bonds)
Nucleic Acid Str uctur e
“
Base Pair ing
”
Sy nthesis Pathway s
For both pur ines and py r imidines ther e ar e
two means of sy nthesis (often r egulate one
another )
• de novo (fr om bits and par ts)
Many Steps Requir e an Activated
Ribose Sugar (PRPP)
de novo Sy nthesis
• Committed step: T his is the point of no r etur n • Occur s ear ly in the biosy nthetic pathway
• Often r egulated by final pr oduct (feedback inhibition)
Feedback inhibitor s: AMP, ADP, GMP, GDP, IMP
AMP ADP AT P R-5-P PRPP PRA IMP
GMP GDP GT P
PRA: 5-phosphor ibosy l-1-amine . activ ation inhibition
Salvage Pathway for Pur ines
Hypoxanthineguanosylphosphoribosyl transferase
(HGPRTase)
Adenine +
PRPP AMP + PPi
Adeninephosphoribosyl transferase
(APRTase)
Hypoxanthine + PRPP IMP + PP
iRegulation of py r imidine nucleotide sy nthesis
CO2 + Gln + AT P
Car bamoy l phosphate
N-Car bamoy laspar tate
UMP
Inhibited by UMP
Inhibited by CTP
-Salv age pathway for py r imidine nucleotide
biosy nthesis
Py r imidine Py r imidine r ibonucleoside
Conclusion
• Nucleotides ar e composed of
5-car bon sugar
,
Base
, and
Phosphate gr oup
• For both pur ines and py r imidines ther e ar e
two means of sy nthesis:
de nov o
Refer ences
• Fr y M. 2011, Essential Biochemistr y for Medicine Wiley
• Gar r ett R.H. et al. 2012 Biochemistr y Br ooks Cole Publishing Company
• Har v ey R.A. et al. 2011 Biochemistr y Wolter s Kluwer Health/L ippincott Williams & Wilkins
• L aemmer hofer M. et al. 2013 Metabolomics in Pr actice: Successful Str ategies to Gener ate and Analy ze Metabolic Data Wiley
• Mathews C.K. et al. 2000 Biochemistr y Benjamin Cummings
• Mur r ay R.K. et al. 2012. Har per ’s Illustr ated