Introduction to Molecular Biology MOLECULAR BIOLOGY 1 Nucleotides

Introduction to Molecular Biology

MOLECULAR BIOLOGY

1 - Nucleotides 2 - DNA 3 - RNA

1 - NUCLEOTIDES 1 - Importance of nucleotides 2 - Structure of nucleotides 3 - Metabolism of nucleotides i. synthesis ii. degradation

Importance of nucleotides 1 - Building units for nucleic acids (DNA & RNA) 2 - Other roles in metabolism & energy storage (discussed later with metabolic pathways)

Structure of nucleotides Nucleotides = nitrogenous base + sugar + phosphate (1, 2 or 3) Nitrogenous base = Purine OR Pyrimidine Sugar = Ribose Purine = Adenine OR OR Deoxyribose Guanine Pyrimidine = Thymine, Cytosine OR Uracil

PURINE RING C N 6 7 N C 1 5 C 8 C 2 C N 3 4 N 9

Pyrimidine RING C 4 N C 3 5 C 2 C N 1 6

b

• Purines : • Pyrimidines: Adenine & Guanine Cytosine, Thymine & Uracil • DNA contains Adenine & Guanine (purines) Cytosine & Thymine (pyrimidines) • RNA contains (pyrimidines) Adenine & Guanine (purines) Cytosine & Uracil

Metabolism of nucleotides 1 - Synthesis (anabolism) i. sources of purine ring atoms ii. sources of pyrimidine ring atoms 2 - Degradation (catabolism) i. end products of purine ring ii. end product of pyrimidine ring

Synthesis of purines: Sources of atoms of purine ring

Synthesis of pyrimidines: Sources of atoms of pyrimidine ring

Degradation (catabolism): End products of purine ring degradation • In human cells purine nucleotides is finally degraded to URIC ACID • Uric acid is transported in blood to kidneys • Finally, Uric acid is excreted in urine • If uric acid is increased in blood --- HYPERURICEMIA (CAUSES? ? ) • Hyperuricemia may lead to ----- GOUT • GOUT is a disease affects joints (arthritis) & kidneys (kidney stones) caused by deposition of uric acid in tissues

Degradation (catabolism): End products of pyrimidine ring degradation Pyrimidine nucleotides are degraded to highly soluble products : b-alanine & b-aminoisobutyrate

DNA 1 - Importance of DNA 2 - Location of DNA in human cells 3 - Structure of DNA molecule - Structure of a single strand of DNA - Structure of double stranded DNA - Linear & circular DNA

Importance of DNA 1 - Storage of genetic material & information (material of GENES) 2 - Transformation of genetic information to new cells (template for REPLICATION) i. e. synthesis of new DNA for new cells 3 - Transformation of information for protein synthesis in cytosol (template for TRANSCRIPTION) i. e. synthesis of m. RNA in nucleus

Structure of DNA molecule

Structure of Single strand of DNA Building Units: Polynucleotide sugar: deoxyribose Purine: A & G Pyrimidine: T & C Polynucleotides are bound together by phosphodiester bonds • If linear DNA: two ends (5` = phosphate & 3` = OH of deoxyribose) • If circular: no ends Sequence of DNA

Structure of double stranded DNA • Two strands are anti-parallel (in opposite directions) • Hydrogen bonds between bases of opposite strands (A & T , C & G) • Denaturation = breakdown (loss) of hydrogen bonds between two strands (melting) leading to formation of two separate single strands) Causes of denaturation ? ? IMPORTANCE ? ? e. g. PCR heating or change of p. H of DNA

Linear & Circular DNA 1 - Linear DNA in nucleus of eukaryotes (include. Human cells) i. e. chromosomes 2 - Circular DNA i. in eukaryotes: mitochondria ii. in prokaryotic chromosomes (nucleoid of bacteria) iii. in plasmids of bacteria (extrachromosomal element) IMPORTANCE ? ? iv. in plant chroroplasts

Replication Semiconservative replication When the two strands of the DNA double helix are separated, each can serve as a template for the replication of a new complementary strand. Each of the individual parental strands remains intact in one of the two new Duplexes (i. e. one of the parental strands is conserved in each of the two new dublexes)

RNA 1 - Structure (differences from DNA) 3 - Types 4 - Importance of each type

Structure of RNA • Building units: Polynucleotides (bound together by PDE) • Single strand • Linear (but may fold into complex structure) • with two ends: 5`(phosphate) & 3`(-OH end) • Sugar: Ribose • Purine bases: Adenine & Guanine • Pyrimidine bases: Cytosine & Uracil

Types & Functions of RNA

Ribosomal RNA (r. RNA) 80% of total RNA in the cell (most abundant RNA) Location: cytosol Function: machine for protein biosynthesis Types:

Transfer RNA (t. RNA) • Smallest of RNAs in cell: 4 S • Location: cytosol • At least one specific t. RNA for each of the 20 amino acids found in proteins • with some unusual bases • with intrachain base-pairing (to provide the folding structure of t. RNA) • Function: 1 - recognizes genetic code word on m. RNA 2 - then, carries its specific amino acid for protein biosynthesis

Messenger RNA (m. RNA) • synthesized in the nucleus (by transcription): DNA (the gene) is used a template for m. RNA synthesis m. RNA is synthesized complementary to DNA but in RNA language i. e. U instead of T So, if A in DNA it will be U in RNA , if T in DNA it will be A in m. RNA…. etc • Carries the genetic information from the nuclear DNA (gene) to the cytosol • In the cytosol, m. RNA is used as a template for protein biosynthesis by ribosomes (with help of t. RNA)…. This is called Translation or Protein Biosynthesis) Transcription + Translation = GENE EXPRESSION

complementary base-pair between DNA & RNA in transcription

Types of m. RNA • Polycistronic m. RNA: One single m. RNA strand carries information from more than one gene (in prokaryotes) • Monocistronic m. RNA: one single m. RNA strand carries information from only one gene (in eukaryotes)

Eukaryotic m. RNA 5`-end: cap of 7 -methylguanosine 3`-end: poly-A tail

The Genetic Code • is a dictionary that identifies the correspondence between a sequence of nucleotide bases & a sequence of amino acids • Each individual word of the code is called a codon is composed three nucleotide bases in m. RNA language (A, G, C & U) in 5`-3` direction e. g. 5`-AUG-3` • The four bases are used by three at a time to produce 64 different combinations of bases 61 codons: code for the 20 common amino acids 3 codons UAG, UGA & UAA: do not code for amino acids but are termination (stop) codons

Genetic Code Table