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 rules in metabolism & energy storage (e.g. ATP is a nucleotide)

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

PURINE RING C 6 N 7 N 1 C 5 C 8 C 2 C 4 N 3 N 9 Purine ring in adenine & guanine

Pyrimidine RING N C N C C C 4 3 5 2 6 1 Pyrimidine ring in thymine, cytosine & uracil

b

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

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, the case is called HYPERURICEMIA Hyperuricemia may lead to GOUT GOUT is a disease affects joints (arthritis) & kidneys (kidney stones) caused by deposition of uric acid in these tissues

Pyrimidine nucleotides are degraded to highly soluble products : 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 mRNA in nucleus

Structure of DNA molecule DNA molecule is formed of double helical strands. (Dounble helix) The two strands are held together by hydrogen bonds Each single strand is formed of polynucleotides Polyncleotides are mononucleotides bound to each other by phosphodiester bonds

Structure of Single strand of DNA Building Units: Polynucleotide sugar: deoxyribose Base: Purine: A or G OR Pyrimidine: T or C Phosphoric acid Mononucleotides are bound together by phosphodiester bonds In linear DNA Strand : two ends (5` = phosphate & 3` = OH of deoxyribose) In circular strand: no ends

Structure of Single strand of DNA Sequence of DNA

Structure of double stranded DNA Hydrogen bonds link the two single strands together 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 leading to formation of two separate single strands) Causes of denaturation : heating or change of pH of DNA

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

DNA Synthesis (Replication) OLD DNA DUPLEX (PARENTAL) DNA synthesis (replication) is the synthesis of new DNA (daughter) duplexes using a template of old (parental) DNA duplex The two strands of the parental DNA double helix are separated, each can serve as a template for the replication of a new Complementary (daughter) 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 DAUGHTER DNA DUPLEXES

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

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

Transcription + Translation Messenger RNA (mRNA) synthesized in the nucleus (by transcription): DNA (the gene) is used a template for mRNA synthesis mRNA 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 mRNA….etc Carries the genetic information from the nuclear DNA (gene) to the cytosol In the cytosol, mRNA is used as a template for protein biosynthesis by ribosomes (with help of tRNA)…. This is called Translation or Protein Biosynthesis) Transcription + Translation = GENE EXPRESSION

complementary base-pair between DNA & RNA in transcription

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

Eukaryotic mRNA 5`-end: cap of 7-methylguanosine 3`-end: poly-A tail

The Genetic Code Each individual word of the 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 a codon is composed three nucleotide bases in mRNA 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