ILA 1 - molecular medicine Flashcards
Describe the process of transcription
Transcription (occurs in nucleus, DNA copied to form mRNA)
- Intiation - RNA polymerase binds to the promotor region
- DNA helicase unzips DNA helix, breaking H bonds
- RNA reads the template strand, and adds bases to 3’ end of growing chain
- RNA polymerase forms H+ bonds between bases - complementary base pairs C-G T-A
- Reaches STOP codon and RNA polymerase releases
- mRNA leaves via pore in nucleus envelope
- RNA splicing removes introns so that just the exons remain
Describe the process of translation
- mRNA binds to the ribosome
- AUG - start codon
initiation
- tRNA binds to the small subunit of ribosome
- amino acyl-tRNA synthetase links amino acids to tRNA
- Initiation factors form an initiation complex
- This positions tRNA opposite the START site codon on mRNA
- The large subunit binds, enclosing the mRNA
elongation
- A ribosome contains 2 binding sites for tRNA, site one holds tRNA linked to protein chain
- Site 2 contains the next amino acids
- tRNA carries amino acids to ribosome to join via complementary base pairing
- Amino acids join via peptide bonds (synthase peptide)
- Ribosome moves along mRNA
- polypeptide chain forms
- Ribosome reaches the STOP codon (UAA, UAC, UGA) and the link between tRNA and chain is broken, the protein is released from the ribosome
Define a single nucleotide polymorphism (SNP)
Single-nucleotide differences in DNA sequence, the change must be present in at least 1% of the general population
How can a SNP alteration in DNA result in a structural change in its protein product, using sickle cell anaemia as an example
- Single nucleotide in coding region could code for another amino acid
- changes primary structure, and secondary and teritary
- affects all bonds
- enzymes have a different confimational shape so cannot form enzyme-substrate-complexes
What are the different bonds in protein structure - primary, secondary, tertiary and quad
Primary - order of amino acids (form peptide bonds)
Secondary - (H+ bonds?) = alpha helix, beta sheets
Tertiary - non covalent interactions -(ionic interactions, hydrogen bonds, van der waals, hydrophobic) sulphur bridges, metal ion interaction = golbular, fibrous, membrane proteins
Quaternary - more than one amino acid chain, linked by non-covalent bonds
How can a functional change in a protein cause external manifestations
Change in amino acid coding, changes bonding, changes conformational shape - complexes
How is sickle cell anemia inherited? -recessive
Sickle cell anemia is a recessive condition, this means that there is a 50% of being a carrier if parent is affected
- need to receive the gene from each of your parents
- must be homogenous in order for the disease to manifest
-mutation in Sc cause valine to be inserted instead of glutamic acid - point mutation at codon 6 - conformational change in shape
What is the difference between homozygous and heterozygous disease?
Homozygous - two of the same gene
heterozygous - two different genes, dominant is the one that presents
Explain the symptoms of sickle cell anemia
- dizziness, fatigue, low oxygen in the body
- can be pain in joints due to blood cramps,
What is a transcriptome?
All the mRNA molecules at one time in one cell
What are the complementary base pairs of DNA and RNA?
DNA
Guanine-H-Cytosine
Adenine-H-Thymine
RNA
Guanine-H-Cytosine
Adenine-H-Uracil
Describe the structure of DNA
Deoxyribonucleic acid
- double helix
- phosphate
- deoxyribose
- phosphate-sugar backbone
Describe the structure of RNA
- Single stranded
- Swaps deoxyribose for ribose
- Uracil for thymine
Adenine-thymine
guanine-cytosine
What are causative single nucleotide polymorphism (SNP)
These are differences in DNA sequence that affect protein function, correlation with disease - they can be coding or non-coding
What are coding and non-coding single nucleotide polymorphisms? (SNP)
Coding SNPs - change amino acid sequence and affect protein structure
Non coding SNPs - located in gene’s regulatory sequence changing timing, location or level of gene expression
What are linked SNPs?
-These changes in nucleotide do not affect protein function but do respond to drugs differently and may have a lower/higher risk of disease
What occurs in the cells of a patient with sickle cell anemia?
- The two beta chains are not formed correctly
- binds to cytoskeleton causing sickle shape
- they are more rigid and cannot carry oxygen as effectively
- can block capillaries - affects endothelial cells causing inflammation
- HbS is less soluble so as oxygen levels decrease it begins to crystallize, Hb molecules then polymerase and RBCs become more sickle shaped
- When you get cold your vessels vasoconstrict this means RBCS cannot travel as easily and can cause pain
What is the structure of hemoglobin?
Two alpha chains, two beta chains, each subunit contains a iron ion (what oxygen binds to)
