CHAPTER 32: NUCLEOTIDES

NUCLEOTIDES
precursor of nucleic acids, purines and
pyrimidines
participate in energy metabolism, CHON
synthesis and enzyme activity regulation
form a portion of many coenzymes
-principal players in energy transduction
UDP glucose and UDP galactose- Participate in
sugar interconversions, starch and glycogen
synthesis
CDP-acylglycerol- lipid biosynthesis
cAMP and cGMP- serve as 2nd messengers in
hormonal events
GTP and GDP- signal transduction pathways
Medical application: purine and pyrimidine
with halogens and thiol are used in
chemotherapy
Pur and Pyr are heterocyclic compounds
Nucleotides are nitrogen-containing
heterocyclic compounds
Pyrimidine- longer name, smaller molecule
Purine- shorter name, larger molecule
Pur and Pyr with NH2 are weak bases: N-1:
adenine, N-7: guanine, N-3: cytosine
Stacking- facilitated by the planar character of
pur and pyr, stabilizes double-stranded DNA
oxo and amino- exhibit keto-enol and amineimine tautomerism
oxo and amino are strongly favored in
physiologic conditions
Nucleosides are N-Glycosides
Nucleosides- derivatives of pur and pyr, have
sugar link to a ring Nitrogen of pur and pyr
sugar in ribonucleoside is D-ribose
sugar in deoxyribonucleoside is 2-deoxy-Dribose
both sugars are linked by -N-Glycosidic bond:
N-1 of pyr, N-9 of pur

Richelle Dianne G Ramos RPh

BIOCHEMISTRY PRELIMS

SEM 2

Nucleotides are phosphorylated nucleosides

mononucleotides are nucleosides w/
phosphoryl group to a hydroxyl group of the
sugar
3and 5 nucleotides- nucleosides with
phosphoryl group in 3 5 hydroxyl group of
sugar
UMP and dAMP- w/ a phosphoryl group on C-5
of pentose
Acid anhydric bond- ligate additional
phosphoryl groups to mononucleotides to form
diphosphate and triphosphate
Heterocyclic N-Glycosides exist as Syn and Anti
conformers
Stearic hindrance- dictates that there is no
freedom of rotation about -N-Glycosidic bond
Nucleosides and nucleotides are
noninconvertible syn or anti conformers
Syn and anti conformers can be interconvertible
by cleavage and reformation of gylcosidic bond
Both syn and anti conformers occur naturally
Anti conformers predominate
PUR-GA : X=H;X=RIBOSE;X=RIBOSE
PHOSPHATE
Purine: Guanine:Guanosine:Guanosine
monophosphate
Purinie:Adenine:adenosine:adenosine
monophosphate
PYR-CUT : X=H;X=RIBOSE;X=RIBOSE
PHOSPHATE
Cytosine;cytidine;cytidine monophosphate
Uracil;uridine;uridine monophosphate
Thymine;thymidine;thymidine monophosphate
Modification of polynucleotides can generate
additional structures
Small quantities of additional pur and pyr occur
in RNA and DNA
5-methyl cytosine- bacterial and human DNA
5-hydroxymethyl cytosine- bacterial and viral
nucleic acid

CHAPTER 32: NUCLEOTIDES

Mono and di-N methylated adenine and
guanine- mammalian mRNA used in
oligonucleotide recognition
Free nucleotides intermediates in catabolism
of adeninde and guanine
Hypoxanthine
Xanthine
Uric acid
Methylated heterocycles- derivatives of
xanthine
Caffeine of coffee
Theophylline of tea
Theobromine of cocoa
Nucleotides are polyfunctional acids
The primary and secondary phosphoryl groups
have pka value of 1.0 and 6.2
Nucleotides bear negative charge at physiologic
pH
Secondary phosphoryl groups act as donor and
acceptor of proton
Nucleotides absorb UV light
Conjugated double bonds absorb UV light
At pH 7, all nucleotide absorb light at 260 nm
Absorbance at 260 nm- expression of
concentration of nucleotides and nucleic acids
Mutagenic effect o fUV light is due to its
absorption by DNA resulting to modification
Nucleosides serve diverse physiologic functions
Mean intracellular conc. of ATP is 1mmol/L
ATP- most abundant free nucleotide in
mammalian cell
Adenosine-3-phosphate5-phosphosulfate Sulfate donor
S- adenosyllmethionine methyl group donor
GTP: allosteric regulator, energy source in
CHON synthesis
cGMP: 2nd messenger in response to NO during
relaxation

Richelle Dianne G Ramos RPh

BIOCHEMISTRY PRELIMS

SEM 2

UDP-sugar epimerization and glycogen

synthesis
UDP glucoronic acid- conjugates of bilirubin
CTP: phosphoglyceride, sphingomyelin synthesis
Nucleoside triphosphates have high-group transfer
potential
Nucleotide trphosphate have 2 acid anhyride
bonds and 1 ester bond
Acid anhydride have high transfer potential
G of a nucleoside triphosphate is -7kcal/mol
Permit pur and pyr nucleoside triphosphates to
fx as group transfer rgts (-phosphoryl)
Transfer of nucleotide monophosphate moiety
with accompanying release of Ppi
Cleavage of acid anhydride bond is coupled with
endergonic process like covalent bond synthesis
Synthetic nucleotide analogs are used in
chemotherapy
Synthetic analogs or pur, pyr, nucleosides and
nucleotides
Toxic effect inhibit enzymes for nucleic acid or
disrupt base-pairing
Allopurinol used in hyperuricemia and gout
inhibits pur synthesis and xanthine oxidase
activity
Cytarabine used in chemo in cancer
Azathiprine is catabolized to 6-mercaptopurine
w/c suppress immunity during transplant
Nonhydrolyzable nucleoside triphosphate analogs
serve as research tool
Allow to distinguish effects of nucleotides due
to phosphoryl transfer from effects of
occupancy of allosteric nucleotide-binding sites
on regulated enzymes.
DNA and RNA are polynucleotides
Phosphodiester- formed when 5-phosphoryl
group esterify a 2nd hydroxyl group (3-OH of
pentose)

CHAPTER 32: NUCLEOTIDES

Dinucleotide- pentose moieties are linked by
3,5-phosphodiester bond to form the
backbone of RNA and DNA
Hydrolysis of phosphodiester bond is strongly
favored
In absence of phosphodiesterases hydrolysis
will occur in a very long time
DNA persist for a long time, even seen in fossils
RNA less stable than DNA
2-hydroxyl group of RNA (absent in DNA) is a
nucleophile during hydrolysis of 35phosphodiesterbond
Polynucleotide post translational modification
can generate structures like pseudouridine
Pseudouridine- D-ribose linked by C to C bond
in C-5 rather than B-N-Glycosidic bond.
Pseudouridylic acid- rearrangement of UMP of a
preformed tRNA
TMP- methylation of S-adenosylmethionine of
UMP of preformd tRNA
Polynucleotides are directional macromolecules
Phosphodiester bond links 3 and 5 of adjacent
monomers
5 end- with free or phosphorylated 5-hydroxyl
Primary structure or base sequence- all
phosphodiester bonds are 3
5 w/c is more
compact notation is possible.

Richelle Dianne G Ramos RPh

BIOCHEMISTRY PRELIMS

SEM 2