NUCLEIC ACID AND

THEIR METABOLISM
 NUCLEOPROTEINS
• Nucleic acids (RNA and DNA) + proteins =
nucleoproteins.
• The non-protein part is the nucleic acid.

• The protein part is mainly histones and protamines.

• They make a large part of nuclear material of the cells.

• They are mainly found in nucleus but are also found in

cytoplasm in association with ribosomes.

 NUCLEIC ACIDS
Nucleic acids are polynucleotides, joined together through
phosphodiester bonds.
• They are present in nucleus. The nucleic acids have two
unique properties i.e. their ability to;
• Reproduce their kind or to store, express and transmit genetic
information.
• Undergo mutation.

Nucleic acids are of two types i.e.

RNA(Ribonucleic Acid)
• It is responsible for protein synthesis.

DNA(Deoxyribonucleic Acid)
• It is basic hereditary unit in humans. It carries genetic
information from one generation to the next.
 COMPONENTS OF NUCLEIC ACIDS
Nucleic acids are made up of three common proteins I.e. nitrogenous base,
sugar and phosphate.
1. NITROGENOUS BASES
There are two groups of nitrogenous bases which are known as purines and
pyramidines.
 Purines: contain adenine and guanine nitrogenous base.
 Pyrimidines: contain thymine, cytocines and uracil nitrogenous bases.

2. SUGAR
Sugar present in nucleic acid is always a pentose i.e. ribose, both in oxidized
and deoxidized forms.
Ribose
(Oxidized form) is present in RNA.
Deoxyribose
(Deoxidized form) is present in DNA.
3. PHOSPHATE
STAGES OF NUCLEIC ACID FORMATION
Nucleoside nucleotide polynucleotide (nucleic acid)
NUCLEOSIDE
 It is nitrogenous base with sugar i.e.
 Adenine + sugar = adenosine
 Guanine+ sugar = guanocine
 Thymine+ sugar = thyomidine( present only in DNA)
 Cytosine+ sugar = cytidine
 Uracil+ sugar = uridine( present only in RNA)
 Adenine, guanine and cytosine can combine with both ribose and
deoxyribose and therefore their nucleosides are present in both DNA
and RNA.
 Uracil combines only with ribose and therefore it is present only in RNA.
 Thymine combines only with deoxyribose and therefore it is present only
in DNA.
NUCLEOTIDE

• It is a nucleoside with phosphate e.g.

• Adenosine + P = Adenosine Monophosphate(AMP) or Adenylic Acid

• Guanosine + P = Guanosine Monophosphate(GMP) or Guanylic Acid

• Thymidine + P = Thymidine Monophosphate(TMP) or Thymidilic Acid

• Cytosine + P = Cytosine Monophosphate(CMP) or Cytidilic Acid

• Uracil + P = Uridine Monophosphate(UMP) or Uridilic Acid

POLYNUCLEOTIDE

• Polynucleotide is a nucleic acid and is formed by joining of many nucleotides

through phosphodiester bonds. In short;

• Nitrogenous base + sugar = Nucleoside

• Nucleoside + phosphate = Nucleotide

 N99 in Purines, N11
in Pyrimidines
C 2’, 3’, 5’

PO44 Ester Sugar -N-glycosidic Base

bond bon
d
 SIGNIFICANCES OF NUCLEOTIDES

They are precursors of DNA and RNA

They are the energy currency in metabolic transactions.

They are components of:

• Cofactors : such as NAD, FAD, S-adenosylmethionine, and

coenzyme A
• Activated biosynthetic intermediates : such as UDP-glucose

and CDP-diacylglycerol.
• Second messengers : such as cAMP and cGMP
OVERVIEW OF NUCLEOTIDE METABOLISM
 NUCLEOTIDE BIOSYNTHESIS

Begins with their metabolic Recycles the free bases and

precursors: amino acids, ribose 5- nucleosides released from
phosphate, CO2, and NH3. nucleic acid breakdown

?Question: Why do we need both pathways

 DE NOVO AND SALVAGE PATHWAYS OF
NUCLEOTIDE SYNTHESIS
De novo pathway is the main synthesis pathway of nucleotides,
the latter is important one in brain and bone marrow. The de
novo synthesis of purine nucleotide means using phosphoribose,
amino acids, one carbon units and CO2 as raw materials to
synthesize purine nucleotide from the beginning.
Salvage pathways are used to recover bases and nucleosides
that are formed during degradation of RNA and DNA. This is
important in some organs because some tissues cannot undergo
de novo synthesis. The salvaged bases and nucleosides can
then be converted back into nucleotides.
Replication
• It is the process of DNA synthesis.
• It occurs during the synthesis-phase of the cell cycle.
• Replication is catalyzed by a complex of protein that includes the
enzyme DNA polymerase
Transcription
• It is the process of gene expression resulting in the synthesis of mRNA
from DNA template.
• The process is catalyzed by RNA polymerase
• Synthesis of messenger RNA (mRNA) is catalyzed by RNA polymerase
I.
• Synthesis of ribosomal RNA (tRNA) is catalyzed by RNA polymerase II.
• Synthesis of transfer RNA (tRNA) is catalyzed by RNA polymerase III.
• After replication change in DNA molecules cause mutations.
• These are result in a permanent alteration of the base sequence in the
daughter DNA.
 PROTEIN SYNTHESIS/TRANSLATION
 Protein synthesis is a highly complex process which is regulated primarily by
DNA it takes place in the ribosomes present in the cytoplasm.
 DNA transmits the information (codons) of protein synthesis to the cytoplasm
through mRNA.
 Each codon is specific for a specific amino acid required for protein synthesis.
 Protein synthesis starts with the ”start codon ” and stops with the “stop codon”
 mRNA take these codons one by one to tRNA which has anti-codons.
 Once the anti-codon on tRNA reads the codon on mRNA, it gets the required
specific amino acid and transfers it to the ribosome containing rRNA.
 rRNA then incorporates that specific amino acid in the growing peptide chain.
This process is known as “translation of genetic code”
 Once the required protein is synthesized completely stop-codon is sent which
stops the protein synthesis. After stop-codon terminates the protein synthesis,
peptidyl transferase gets activated and release the synthesized protein.
 NUCEIC ACID METABOLISM
• Nucleic acids (DNA and RNA) are catabolized under the influence of
nucleases
• The nucleases for DNA are called deoxyribonucleases or DNA ases.
• The nucleases for RNA are called ribonudeases or RNAases.
• Breakdown of polynucleotides (DNA and RNA ) result in the release
of mononucleotides.
• The mononucleotides by the action mcleotidases produce
nucleosides +H3PO4 e.g.
19
PURINES CATABOLISM (URIC ACID FROMATION)
• The nucleosides undergo further catabolism as described below
under purines and pyrimidine.
PURINES CATABOLISM (URIC ACID FROMATION)
• The catabolism starts with nucleosides i.e. adenosine and
guanosine.
CATABOLIC REACTIONS
 The reaction catalyzed by adenase is not important for humans
because the enzyme adenase is not found in human tissues.
However if free adenine occurs in excess in the body it is
converted to 2, 8 – dihydroxyadenine
 2, 8- dihydroxyadenine can cause renal damage by forming
crystals in the renal substance.
 In humans nucleosides (adenosine and guanosine ) are
DEGRADATION OF PYRIMIDINE NUCLEOTIDE
• The pyrimidine ring can be completely degraded in humans.

• The products include: NH3, CO2, b-alanine, and b-

aminoisobutyrate.

• Both b-alanine, and b-aminoisobutyrate can be further

converted into acetyl-CoA and succinyl-CoA, respectively, or
are excreted in the urine.
 CLINICAL NOTES PURINE CATABOLISM
• It is defined as the excessive accumulation of uric acid (Mono-sodium
Urate Crystals) in the joints especially in knuckles and big toe. It is
characterized by episodes of acute arthritis with or without raised uric
acid levels in the blood.
• The accumulations of monosodium urate crystals in cartilage tissue
tendons and soft tissues are known as tophi.
• Deposition of urate crystals in the metatarsophalangeal joins of big toe
is known as podagra.
• Gout often leads to renal failure due to interstitial deposition of urate
crystals and obstruction of collection tubules by forming urate and
calcium stones.
• Diagnosis is made by polarizing microscopy for synovial fluid of joints
or bursas or of material aspirated from tophi (if any). Under polarized
microscopy these aspirates (synovial fluid and tophaceous material)
show negatively birefringent monosodium urate crystals.
 XANTHINURIA
• In this disorder large amounts of xanthine are excreted in urine

• The uric acid content of the urine is decreased

• Serum uric acid level is also very low.

• It is due to the absence of the enzyme xanthine oxidase. Therefore

the body fail to convert xanthine into uric acid

• Excess amount of xanthine in the urine causes the formation of

xanthine cause
• Xanthine calculi are not opaque to x-ray and can be easily missed

• Administration of allopurinol also increases the urinary excretion of

xanthine because it decreases the formation of uric acid by

competitively inhibiting the enzyme xanthine oxidase.
 PYRIMIDINES CATABOLISM
• The steps of the catabolism are not important to remember.
• At the end of pyrimidine catatbolism cytosine and uracil are converted
to Acetyl CoA and succinyl-S-CoA which eventually enters citric acid
cycle e.g.

• Thymine at the end of pyrimidine catabolism is converted to succinic

acid which also enters citric acid cycle e.g.