Genes, Health, and Exchange

• Topic 2 is about Genes and Health

Gas Exchange

• Gas exchange rate increases with larger surface area, decreased diffusion distance, and steeper diffusion gradient
• Fick's Law states diffusion rate is proportional to surface area times concentration difference, divided by diffusion distance
• Mammalian lungs facilitate rapid gas exchange via large surface area from alveoli
• Good blood supply maintains a steep concentration gradient, and a short diffusion distance due to thin alveoli

Cell Membrane and Transport of Substances

• Cells are surrounded by partially permeable membranes made of phospholipids and proteins
• Membranes control substance movement, contain receptors, and allow cells to stick together
• The fluid mosaic model describes the membrane structure
• Molecule movement depends on properties and cell requirements
• Diffusion is passive movement of small, non-polar molecules from high to low concentration areas
• Facilitated diffusion uses channel proteins for polar, charged, and water-soluble molecules
• Osmosis involves water molecule movement from low to high solute concentration areas through a partially permeable membrane
• Active transport uses carrier proteins and ATP energy to move all molecule types, with or against the concentration gradient
• Endocytosis/exocytosis transport large particles using vesicles, both are active

DNA Structure

• A mononucleotide consists of:
  • Purine bases: adenine, guanine (two-ring)
  • Pyrimidine bases: cytosine, thymine (one-ring)
  • A-T and C-G pairing
  • Deoxyribose sugar
  • Phosphodiester bonds
  • Hydrogen bonds hold the structure together
• Structure is double-stranded, alpha double helix with a sugar-phosphate backbone
• mRNA has:
  • Purine bases: adenine, guanine
  • Pyrimidine bases: cytosine, uracil
  • A-U and C-G pairing
  • Ribose sugar
  • Bonds as DNA
• mRNA carries codons (triplets of bases) and attaches to tRNA via hydrogen bonds
• tRNA has mRNA bases, pairing, sugar, and bonding
• tRNA is single-stranded, folded, carries anticodons complementary to mRNA codons

Protein Synthesis

• Protein synthesis includes transcription (nucleus, DNA/mRNA) and translation (ribosomes, mRNA/tRNA)
• During transcription, DNA is transcribed into mRNA; during translation, amino acids form a polypeptide chain/protein

Transcription

• mRNA is made in the nucleus
• Hydrogen bonds break, and DNA uncoils, separating strands
• One DNA strand (antisense) is the template for mRNA
• Free nucleotides line up by complementary base pairing
• Phosphodiester bonds join nucleotides, forming mRNA, catalyzed by RNA polymerase
• mRNA moves out and attaches to a ribosome in the cytoplasm

Translation

• Amino acids combine to form a polypeptide chain
• mRNA attaches to a ribosome, tRNA binds amino acids, known as activation
• tRNA anticodons bind to mRNA codons with hydrogen bonds
• Ribosomes join amino acids via peptide bonds, tRNA detaches
• This process repeats until a stop codon is reached on mRNA

Genetic Code

• A gene is a DNA base series coding for amino acids in a polypeptide chain
• The order of bases is the genetic code, consisting of base triplets
• Each triplet codes for an amino acid, joined by peptide bonds
• Genes are DNA sequences coding for amino acid sequences in polypeptide chains
• Introns are non-coding DNA sections, exons are coding regions

Genetic Code Features

• Each triplet is read once, triplets are non-overlapping
• Degenerate means more than one triplet codes for the same amino acid
• Each three bases codes for one amino acid
• Contains start and stop codons

Proteins

• Proteins are made from amino acids
• Amino acids contain an amino group, carboxyl group, and variable R group
• There are 20 amino acids and they are joined by peptide bonds in condensation reactions
• A dipeptide has two amino acids, polypeptides have three or more

Protein Structure

• The structure is determined by amino acid order/number, bonding, and shape
• Primary structure is the amino acid sequence
• Secondary structure is the 2D arrangement: alpha helix or beta pleated sheet
• Tertiary structure results in 3D folding due to hydrogen, ionic, and disulphide bonds
• Quaternary structure is the arrangement of multiple polypeptides
• Proteins can be fibrous or globular

Fibrous Proteins

• Long, parallel polypeptide chains
• Very little tertiary/quaternary structure
• Have occasional cross-linkages form microfibres for tensile strength
• Fibrous proteins are insoluble, used for structural purposes such as collagen

Globular Proteins

• Complex tertiary/quaternary structures
• Form colloids in water
• Used as hormones, antibodies, carrier proteins, like haemoglobin
• Collagen has high tensile strength due to hydrogen and covalent bonds
• Collagen molecules consist of three polypeptides forming an alpha triple helix and strong collagen fibres
• The role of collagen is that it forms bones cartilage, connective tissue, tendons
• Haemoglobin is a water-soluble protein of four polypeptide chains and a haem group
• Haemoglobin carries oxygen, bound in the haem (Fe²⁺) group, releasing it when needed

Enzymes

• Enzymes increase reaction rates by lowering activation energy
• They catalyze anabolic, catabolic, intracellular, and extracellular reactions
• The active site is where the substrate binds and is specific to the substrate
• The lock and key model used to describe enzyme action
• A more recent model is the induced-fit theory
• Enzymes distort to fit the substrate
• Initial reaction rate is measured by calculating the gradient of a concentration-time graph

Factors Affecting Enzyme-controlled Reactions

• Enzyme concentration: rate increases with enzyme concentration, until substrate concentration becomes limiting
• Substrate concentration: rate increases with substrate concentration, until enzyme concentration becomes limiting
• Temperature: rate increases to the optimum, then decreases due to denaturation
• pH: enzymes work within a narrow range; extremes alter bonds and shape

DNA Replication

• DNA replication ensures genetic continuity between generations
• Semiconservative replication proven by Meselson-Stahl experiments
• In an experiment, DNA grown in N15 was transferred to N14, resulting in hybrid DNA strands
• Subsequent replication resulted in hybrid and entirely N14 strands, supporting semi-conservative replication

Steps in Semiconservative Replication

• The double helix unwinds
• Hydrogen bonds break, catalyzed by DNA helicase, separating strands
• One strand is the template for complementary base pairing with free nucleotides
• Adjacent nucleotides are joined by phosphodiester bonds to form condensation reactions
• DNA polymerase performs these reactions

Cystic Fibrosis Mutations

• Mutations are a permanent change in DNA
• Gene mutations alter base arrangement
• This includes Substitution (change in one base)
• Insertion (adding another base in)
• Deletion (taking a base out)
• Duplication (adding the same base more than once)
• Inversion (swapping the order of bases)
• The change in base impacts mRNA, tRNA, and protein
• Cystic fibrosis is a genetic disorder caused by mutation in a gene coding the CFTR protein (channel protein which transports chloride ions)

CFTR

• It is a channel protein which transports chloride ions out of respiratory tract cells into mucus
• This makes the mucus watery by osmosis
• A mutation makes thick mucus because the mutant cannot transport chloride ions.
• Thick mucus causes problems in gas exchange, reproduction, and digestion

Cystic Fibrosis impact on the Respiratory system

• Mucus buildup in the lungs traps bacteria and increases infection risk
• Mucus buildup decreases surface area of alveoli, reducing gas exchange

Cystic Fibrosis impact on the Reproductive System

• In women, cervical mucus prevents sperm from reaching the egg
• In men, the sperm duct is blocked by mucus

Cystic Fibrosis impact on the Digestive System

• The pancreatic duct can get blocked, so digestive enzymes do not reach the small intestine, so nutrients aren't absorbed
• Duodenum lining is very thick, reducing nutrient absorption
• Pancreatic cysts can damage insulin-producing cells, leading to diabetes

Genetics Terminology

• Gene is a DNA piece with a specific base sequence and codes for a protein
• Allele: one of the different forms of a gene
• Genotype: all the alleles of an organism
• Phenotype results from the interaction of genotype and environment

Allele Types

• Recessive: produces a feature only if two copies are present
• Dominant: produces a feature if one copy is present
• Incomplete dominance: a form of intermediate inheritance in which one allele for a specific trait is not completely expressed over its paired allele
• Homozygote: an individual with two identical alleles
• Heterozygote: an individual with two different alleles

Monohybrid Inheritance

• Monohybrid inheritance is based on inheritance of a single characteristic

Genetic Screening

• Genetic screening determines if DNA contains gene disorder alleles
• Genetic screening is used to identify carriers and for preimplantation and prenatal genetic diagnosis
• Pre-implantation genetic diagnosis tests IVF embryos for disorders before implantation
• Chorionic villus sampling is performed at 8-12 weeks
• A sample of embryonic tissue taken from the placenta and analyzed
• Amniocentesis (14-16 weeks) analyzes amniotic fluid containing fetal cells
• Genetic testing presents social and ethical issues, including:

Ethical Issues of Genetic Screening

• The risk of harm to the fetus or miscarriage
• The possibility of aborting the right to life
• The cost of raising a child with a genetic disorder
• The emotional and mental toll of caring for such babies