Biology Unit 5.1.1- Cellular Control

Biology Unit 5.1.1- Cellular Control

1. How DNA codes for proteins

   • Key Words:
     • genes- a length of DNA that codes for one or polypeptide chains
     • polypeptide- polymer consisting of a chain of amino acid residues joined by a peptide bond.
     • genome- entire DNA sequence of one organism. Human genomes consist of 3 billion nucleotide base pairs
     • Protein- Large polypeptide (100+ amino acids) some proteins consist of more than one polypeptide chain
   • A gene is...
     • sequence of nucleotide bases that code for polypeptides
     • human genome = 25 000 genes (some in mitochondria and linear chromosomes)
     • occupies locus on chromosome
     • codes for polypeptides such as...
       • haemoglobin
       • immunoglobulins
       • antigens
       • enzymes
       • electron carriers
       • structural proteins
       • cell surface receptors
       • actin and myosin
       • tubulin
       • channel
   • Genetic code
     • triplet code- 3 nucleotide bases that code for an amino acid (20 acids) 4x4=16 not enough, 4x4x4=64 more than enough
     • Degenerate code- All amino acids have more than one code (Not MET)
     • Stop codons at end of chain
     • wide spread info, not universal
   • Protein Synthesis, 1st Step- Transcription
     • Free DNA nucleotides in the nucleoplasm and free RNA nucleotides in nucleolus. Nucleotides are activated (Have 2 extra phosphoryl groups)
     • 4 Different activated RNA nucleotied: ATP, GTP, CTP, UTP
     • Steps:
       • 1. DNA that makes up gene dips out of nucleolus. H+ Bonds break and DNA molecule unwinds and unzips.
       • 2. RNA nucleotides bind with Hydrogen bonds: U-A, G-C, A-T (on template strand). catalysed reaction with RNA polymerase
       • 3. Two extra phosphoryl groups needed. Released Energy for bonding adjacent nucleotides
       • 4. mRNA produced = complementary to nucleotide Base sequence on template therefore, copy of base sequences on coding strand of the length of DNA
       • 5. mRNA released from DNA and passes out of the nucleus, through a pore to the ribosome

2. Translation- 2nd Step of Protein Synthesis

   • Translation is...
     • assembly of polypeptides (proteins) at ribosomes
     • second stage of protein synthesis (amino acids assembled into polypeptides)
     • assembled according to codon (triplets of nucleotide bases.
     • occurs in ribosomes
   • Ribosomes...
     • assembled in nucleolus of eukaryote cells from ribosomal RNA and protein
     • move along mRNA through groove- reads code and assembles amino acids in correct order to form a functional protein
     • sequence of amino acids important because...
       • forms primary structure (determines tertiary structure), how its held in 3D form with hydrogen or ionic bonds, hydrophobic reactions between R groups, tertiary structure allows protein to function, if altered cant function properly
   • Transfer RNA (tRNA)
     • made in nucleus and pass into cytoplasm
     • length of RNA that folds into hairpin (clover) shape
     • 3 exposed bases where a particular amino acid can bind
     • on other end: 3 unpaired nucleotide bases- anticodon. each binds temporarily with complimentary codon
   • Steps:
     • 1. mRNA binds to ribosomes- Translation begins. AUG codes for Methonine. Anticodon of tRNA forms base pairs with codon on mRNA
     • .2. Another tRNA molecule (Serine) occupies second spot in ribosomes. Peptide bond formed with MET and SER
     • 3. Ribosomes move one codon along mRNA. MET tRNA leaves and another arrives and occupies next vacant position. tRNA ensures genetic message is read correctly
     • 4. Ribosome moves on and add on more amino acids to polypeptide chain. carries on until stop codon appears (UAA, UAG, UGA). Translation is complete
   • Some proteins activated by cAMP which activates them by changing 3D shape so its easier to fit their complementary molecule
   • Protein Synthesis in Prokaryoes- Translation begins as soon as mRNA made because DNA not held in a nucleus

3. Mutations

   • Key Words...
     • Mutations- change in amount of or arrangement of genetic material in a cell (randomly occuring)
     • chromosome mutations- change to part or whole chromosome. Changes to the structure such as deletion, inversion and translocation.
     • DNA mutations- changes to genes due to changes in nucleotide base sequences
   • Occurs during replication. substances may cause mutations- Tar, UV, X/Gamma rays
   • DNA Mutations
     • Occur during nuclear division
       • Meiosis- can be passed to offspring
       • Mitosis- Somatic mutations- not passed to offspring, contributes ot ageing process/cancer
     • 2 Types:
       • 1. Point Mutations- one base pair replaces another- Substituted base pair
         • Cause:
           • Missense: is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid
           • Nonsense: mutation causes a stop in the polypeptide chain. therefore, not a full chain and cant form any functions
           • Silent Mutations- Mutation within triplet code that doesnt affect the amino acid or polypeptide chain
       • 2. Insertion/Deletion mutations- 1+ nucleotide pairs inserted or deleted from DNA. Causes a Frameshift
         • Causes Frameshift, deletion of one gene that causes a frameshift because of this, different amino acids would form with no stop codon
   • Diseases due to mutations:
     • Deletion of Triplet base pair = deletion of amino acids from approx 1480 amino acids in normal polypeptide chain: Cystic Fibrosis
     • Mutation on Codon 6 for Beta polypeptide chains of haemoglobin cause valine to be inserted rather than glutamic acid: Sickle Cell anaemia
     • repeated CAG sequence if expand a threshold number protein is altered sufficiently: Huntingtons
   • Neutral effects
     • allele- alternate version of a gene, still at same locus on chromosome and cods for some polypeptides but alterations to base alters structure
     • may not change organisms if...
       • in non coding region of DNA
       • silent mutations
     • change/mutation may not have an advantage or disadvantage and so has neutral effects.
   • harmful or beneficial effects:
     • early human melanin protected harmful effects of UV light, but can still synthesis Vitamin D
     • mutations to skin colour gene (pale skin, would have more burns and suffer skin cancers)
     • migration to more temperate climates, sun not intense enough for Dark.
     • Those with paler skins would be advantaged as they can synthesis Vitamin D
       • Low vitamin D...
         • rickets
         • narrow pelvis
         • Cancer
         • Heart disease

4. The Lac Operon

   • Enzyme induction
     • enzymes involved in basic cellular functions are synthesised at a constant rate
     • inducible enzymes synthesised at variable rates according to cell circumstances
     • Bacteria adapt to their environment by producing enzyme to metabolise certain nutrients only when present
     • E coli repress glucose but also use lactose as a respiratory substance
     • E coli grown with no lactose can be placed where there is lactose. at first they cant metabolise lactose because they have small amounts of the 2 enzymes to metabolise. the two enzymes are:
       • Beta galactosidase- catalyses the hydrolysis of lactose to glucose and galactose
       • Lactose Permease- transports lactose into cells
     • when added to lactose environment, bacteria increases rate of synthesis of the 2 enzymes (inducer)
   • Lac System Genes form an Operon
     • Regulatory Gene- Not part of operon, a gene involved in controlling the expression of one or more other genes.
     • Structural Genes
       • Z: codes for- Beta Galactosidase
       • Y: Codes for- Lactose Permease
       • each consists of sequence of base pairs that can transcribe to mRNA
     • Opperator region- switches genes on and off
     • Promoter region- RNA polymerase binds to begin transcription of structural genes
   • Absent Lactose
     • 1. Regulatory gene expressed, repressor protein synthesised. 2 binding sites: lactose and opperator region
     • 2. repressor protein binds with opperator region and covers promoter where RNA polymerase normally attaches
     • 3. Structural genes not transcribed
     • 4. without mRNA, gene cant be transcribed, both enzymes not synthesised
   • With Lactose
     • 1. lactose binds to site on repressor protein, causes repressor to change shape and cant bind with operator. Lactose = inhibitor
     • 2. Promotor region remains unblocked, RNA polymerase binds and initiates transcription of mRNA for Z and Y genes
     • 3. operator-repressor-inducer system acts as switch and allows transcription and subsequent translations of Z and Y into Lac enzyme
     • 4. E coli can use lactose permease to bring lactose into cell and convert lactose to glucose and galactose with beta galactosidase. sugars used for respiration and gaining energy from lactose

5. Genes and Body Plans

   • Drosophilia development
     • 1. one miotic division every 6-10 mins
     • 2. no new cell membranes and multi-nucleate syncytium formed.
     • 3. 8th division- 256 nuclei migrate to outerparts
     • 4. 11th division- nuclei form outer layer around central yolk filled core.
     • 5. 14th Division- slows down (60 mins). nuclear genes switch from replicate to transcribe
     • 6. membrane invaginates around 6000 nuclei. therefore, cells form single outer layer
     • 7. 2-3 hours- embryo develops into segements corresponding to organisation of organisms body plans. Md, Mx, Lb= Head; T1-T3= Thoracic; A1-A8= abdominal
     • 8. Metamorphisis- legs, wings, antennae.
     • Genetic control
       • Homeobox genes: controls development of body plans of an organism (Polarity, position of organs)
       • maternal effect genes- polarity
       • segmentation genes- polarity of segments
   • Genetic control of development in other organisms
     • Homeobox genes contain 180 base pairs therefore, polypeptides of 60 amino acids
     • Hox clusters- arrangements of homebox genes
       • Nematodes (roundworms)- 1 Hox Clusters
       • Drosophilia- 2
       • Vertebrates- 4, 9-11 genes, separate chromosomes
   • Retinoic Acid and birth defects- too much retinoic acid (Vitamin A) interferes with expression of genes therefore, birth defects may iccur. Vitamin A activates homeobox genes

6. Apoptosis

   • Programmed cell death
   • hayflick constant- 50 miotic divisions that undergo a series of biochemical events before tidy cell death
   • necrosis- messy cell death
   • How is it controlled? Cell signaling
     • Cytokines (made by cells immune system)
     • hormones
     • nitric oxide- induces apoptosis by making inner mitochondrial membrane permeable to H+ and dissipitates proton gradient
   • Development
     • Children (8-14): 20-30 billion cells a day
     • Adults: 50-70 billion cells a day
     • too little apoptosis: tumours, cancers
     • Too Much: cell loss, degeneration
   • Steps
     • 1. enzymes breakdown cell cytoskeleton, cytoplasm becomes dense, organelles tightly packed
     • 2. cell surface membrane invaginates and blebs form. chromatin condenses.
     • 3. Nuclear envelop breaks down, DNA breaks into fragments, cell breaks into vesicles
     • 4. Vesicles taken up by phagocytosis. cellular debris disposed of and doesnt damage other cells and tissues. Quick process