Introduction to Introduction to Molecular BiologyMolecular Biology

MOLECULAR BIOLOGY

1- Nucleotides2- DNA3- RNA

1 -NUCLEOTIDESNUCLEOTIDES

1- Importance of nucleotides

2- Structure of nucleotides

3- Metabolism of nucleotides i. synthesis ii. degradation

Importance of nucleotidesnucleotides

1 -Building units for nucleic acids (DNA & RNA)

2 -Other rules in metabolism & energy storage

( e.g. ATP is a nucleotide )

Structure of nucleotidesnucleotides

NucleotidesNucleotides = nitrogenous base + sugar + phosphate (1,2 or 3) = 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 RINGPURINE RING

C6

C5

N3

N1

C2

C4

N7

C8

N9

Purine ring in adenine & guaninePurine ring in adenine & guanine

Pyrimidine RINGPyrimidine RING

C4

C5

N1

N 3

C2

C6

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 purinesSynthesis of purines::Sources of atoms of purine ring

Synthesis of pyrimidinesSynthesis of pyrimidines:Sources of atoms of pyrimidine ring

Degradation (catabolism)Degradation (catabolism):End products of purine ring degradation

• In human cells purine nucleotides is finally degraded to URIC ACIDURIC ACID

• Uric acidUric acid is transported in blood to kidneys

• Finally, Uric acidUric acid is excreted in urine

• If uric acid is increased in blood, the case is called HYPERURICEMIAHYPERURICEMIA

• Hyperuricemia may lead to GOUTGOUT

• GOUTGOUT is a disease affects joints )arthritis( & kidneys )kidney stones( caused by deposition of uric acid in these tissues

Pyrimidine nucleotides are degraded to highly solublesoluble products:

-alanine & -aminoisobutyrate

Degradation (catabolism):End products of pyrimidine ring degradation

DNADNA

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

ImportanceImportance of DNAof 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

StructureStructure of DNA moleculeof DNA molecule

DNA molecule is formed of double helical strands.DNA molecule is formed of double helical strands.)Dounble helix( )Dounble helix( The two strands are held together by The two strands are held together by hydrogen bondshydrogen bonds

Each single strand is formed of Each single strand is formed of polynucleotides polynucleotides

Polyncleotides are Polyncleotides are mononucleotidesmononucleotides bound to bound to each other by each other by phosphodiester bonds phosphodiester bonds

Structure of Structure of Single strand Single strand of DNAof DNA

Building Units: Polynucleotide sugarsugar: deoxyribose BaseBase: Purine: A or G OR Pyrimidine: T or C

Phosphoric acidPhosphoric acid Mononucleotides are bound together by phosphodiester bondsphosphodiester bonds

In linear DNA Strand : two ends )5` = phosphate & 3` = OH of deoxyribose(In circular strand: nono ends

Structure of Structure of Single strand Single strand of DNAof DNA

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(

DenaturationDenaturationbreakdown )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

Hydrogen bonds linkHydrogen bonds link the two single strands togetherthe two single strands together

Linear & Circular DNALinear & Circular DNA

1- Linear DNA 1- Linear DNA

in nucleus of eukaryotes (including human cells) i.e. DNA of chromosomes

2-2- Circular DNACircular 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 DNA Synthesis )Replication)

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 newComplementary (daughter) strand.

Each of the individual parental strands remains intact in one of the two new Duplexesi.e. one of the parental strands is conserved in each of the two new dublexes

OLDOLD DNADNA

DUPLEXDUPLEX((PARENTALPARENTAL))

DAUGHTERDAUGHTER DNADNA

DUPLEXESDUPLEXES

RNARNA

1- StructureStructure (differences from DNA)3- TypesTypes4- Importance of each typeImportance of each type

Structure of RNARNA

• 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 RNARNA

Ribosomal RNA (Ribosomal RNA (rRNArRNA))

80% of total RNA in the cell (most abundant RNA)Location: cytosolFunction: machine for protein biosynthesisTypes:

Transfer RNA (Transfer RNA (tRNAtRNA))

• 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

• 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

Messenger RNA (Messenger RNA (mRNAmRNA))

complementary complementary base-pairbase-pair between DNA & RNA between DNA & RNAin transcriptionin transcription

Types of mRNATypes of mRNA

• PolyPolycistronic cistronic mRNAmRNA:: One single mRNA strand carries information from more

than one gene )in prokaryotes(

• MonoMonocistroniccistronic mRNA: mRNA: one single mRNA strand carries information from only one

gene )in eukaryotes(

Eukaryotic Eukaryotic mRNAmRNA

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 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