Regulation Of Gene Expression Flashcards
What is a gene?
General definition: Basic unit of inheritance of a characteristic.
Biological definition: Sequence of nucleotides in DNA ( a segment) that is transcribed to produce a functional RNA.
Genes act as instructions for the synthesis of aspecific protein (e.g. an enzyme)
State the structure of a gene
DNA & RNA are nucleic acids made up of nucleotides.
NUCLEOTIDES are made up of nitrogenous bases( Purines and Pyrimidines) , Sugar( Ribose and Deoxyribose) and a phosphate group
List the types of nitrogenous bases and their subtypes
PURINES( Adenine and Guanine)
PYRIMIDINES ( Cytosine, Thymine, Uracil)
State the modified and other bases that make up nucleotides
MODIFIED BASES: 3 methyl cytosine, 5 OH methyl cytosine and methylated guanine in mRNA.
OTHER BASES: Hypoxanthine, xanthine, uric acid
What are the functions of nucleotides?
- Form of energy in the cell- ATP,GTP,UTP
- Intermediates in metabolic reaction- UDPglucose.
- Second messengers-cAMP
- Coenzymes: NAD, FAD & Coenzyme A.
- Building blocks of nucleic acids
Describe the synthetic bases and anti-metabolites that are used in therapy
A. 5Fluorouracil: Analogue of Uracil. it is converted to 5 Flourouracil monophosphate an inhibitor of thymidylate synthase that catalyses the conversion deoxyuracil monophosphate to deoxy thymine monophosphate.
B. methotraxate: Analogue of dihydrofolate. It inhibits dihydrofolate reductase that catalyses the reduction of Dihydrofolate to tetrahydrofolate an esssential coenzyme in DNA synthesis. Rapidly dividing cells like cancer cells are more susceptible.
C. Allopurinol:- Analoque of xanthine and hypoxanthine. It inhibits the enzyme xanthine oxidase.
Via which pathways are nucleotides synthesized?
De novo
Salvage
Briefly describe the de novo synthesis of nucleotides
Purine ring: synthesized while attached to Ribse 5 Phosphate. synthesis from simple molecules amino acids glycine, glutamine and aspartate, carbon dioxide and formate donated by tetrahydrofolate
Pyrimidine ring: the pyrimidine ring is attached to ribose 5 phosphate after the ring has been synthesized. The synthesis of pyrimidine begins with the construction of the nitrogenous base and ends with the addition of the sugar and phosphate group
What happens in the salvage pathway of nucleotides?
Nitrogenous bases and nucleosides from the breakdown of old nucleotides are recycled to synthesize new nucleotides
Draw the purine structure and identify the sources of its atoms
Nitrogen 1(N1) = aspartate.
Carbon 2(C2)= N10 formyl tetrahydrofolate.
Nitrogen 3( N3)= amide nitrogen of glutamine.
Carbon 4, carbon 5 and nitrogen 7 ( C4,C5, N7)= glycine
Carbon 6( C6) = carbon dioxide
Carbon 8(C8) = N10 formyl tetrahydrofolate.
Nitrogen 9( N9)= amide nitrogen of glutamine.
Outline the reactions in purine biosynthesis
- Ribose 5 P + ATP →5-phosphoribosylpyrophosphate+ AMP (PRPP SYNTHETASE) committed step
- 5-phosphoribosylpyrophosphate +glutamine→ 5-phosphoribosylamine +PPi+ glutamate (PRPP AMIDOTRANSFERASE/ Glutamine PRPP amidotransferase)
- 5- phosphorobosylamine +glycine+ ATP→ 5-phosphoribosyyglycinamide + ADP + Pi (5- phosphoribosyl glycinamide SYNTHETASE/GAR Synthetase)
- Glycinamide ribonucleotide + formyl T4F → formyl glycinamide ribonucleotide + T4F (GAR TRANSFORMYLASE) FIRST OF 2 THF DEPENDENT RX
- FGAR +glutamine+ ATP → formyl glycinamidine ribonucleotide + ADP+ Pi (FGAR AMIDO TRANSFERASE)
- FGAM + ATP→ 5-amino imidazole ribonucleotide ADP+ Pi (glycinamidine ribonucleotide CYCLASE)
- AIR + CO2→ carboxyamino imidazole ribonucleotide (AIR CARBOXYLASE)
- CAIR + aspartate + ATP → N succinylo 5 amino imidazole 4 carboxamide ribonucleotide+ ADP +Pi (SAICAR SYNTHETASE)
- SAICAR → N 5 amino imidazole carboxamide ribonucleotide+ fumarate (adenylo succinate LYASE)
- AICAR + formyl T4F → FAICAR + T4F (AICAR TRANSFORMYLASE)
- FAICAR → inosine monophosphate + H2O (IMP SYNTHASE)
Once formed, IMP is rapidly
converted to AMP and GMP
Draw the pyrimidine structure and identify the sources of its atoms
The sources of atoms of the pyrimidine ring.
C2 and N3 = carbamoyl phosphate
C4, C5, C6 and N1 = aspartate
What metabolic defects can result from purine synthesis?
Gouty arthritis,
Lesch Nyhan disease
What metabolic defects can result from pyrimidine synthesis?
orotic aciduria types 1 and 2
What are the fundamental features of replication?
i) semi conservative,
ii)begins at the origin and proceeds bidirectional at the replication folk,
iii) semi discontinous
Briefly state the functions of the main enzymes involved in replication
DNA Polymerase I (gap filling, repair and recombination.
DNA Polymerase II(proof reading and repair).
DNA Polymerase III processitivity{ number of nucleotides added before the enzyme dissociates} and strand synthesis)
What are histones?
proteins attached to chromosomes. have a role to play in gene expression
What are the mutations seen in sickle cell due to replication fault?
For example point mutation seen in Sickle Cell.
Glutamate Codon
GAA GUG
GUU
GUC
Valine Codon GUA
GAG
List the type of DNA damage
- Single base alteration- deamination of cytosine to uracil, Insertion or deletion of a nucleotide.
- Two Base alterations . Formation of thymine dimer
- Chain breaks by UV light
What are the mechanisms of DNA repair?
Mismatch repair.
Nucleotide excision.
Base excision repair
Briefly describe transcription
Only one strand serves as a template- the template strand.
The other strand is the coding strand and runs in the same direction as the RNA molecule that is being transcribed( 5’ to 3’ direction).
Initiation, elongation, termination, post transcription modification.
RNA: Single stranded They are Four types( mRNA,rRNA,tRNA and sRNA)
Briefly describe translation
The linear sequence of DNA that was transcribed into mRNA is translated into linear sequence of amino acid residues of a protein
The mRNA sequence that specifies for the AA sequence in the protein is called the genetic code with 64 triplet codons.
The features of the genetic code.
The stages of protein synthesis.
Describe the first step of gene expression
THE TRANSCRIPTION OF THE SEGMENT OF DNA INTO RNA.
Transcription is a regulated process that allows a cell or organism to adapt to environmental changes. For example, it controls on when a protein should be produced and how much.
Gene expression process involves modulation(control) of Gene Transcription
In the control of gene transcription specific regulatory proteins bind to regions of DNA in the controlled gene which causes: positive(activate) or negative(inhibit) effect on transcription.
Explain the mechanism of gene regulation / transcriptional control
- Using specific binding proteins that bind to the regulatory (promoter) segment of a gene.
- Gene regulation is influenced by chemicals such as hormones.
- Gene expression can also be modulated by gene amplification which leads to increase in the number of copies of the gene. This is seen in cancer cells which cause the cancer cells to grow and multiply uncontrollably.
- Gene rearrangement mechanisms. Reconstitute a gene from gene segments in gene recombination. This is seen in Genetically Modified Organisms.
- Post transcriptional modifications of RNA also contribute to control of gene expression
