Molecular Genetics and Protein Synthesis

DNA Transcription and mRNA Processing

Transcription is the process by which genetic information from DNA is copied into messenger RNA (mRNA) for protein synthesis. This process involves several steps and key molecules.

• DNA Unwinding: DNA is unwound by helicase to expose the template strand for transcription.

• Template and Coding Strands: The template strand is used for mRNA synthesis, while the coding strand has the same sequence as the mRNA (except T is replaced by U in RNA).

• Directionality: Transcription proceeds in the 5' to 3' direction.

Processing of pre-mRNA to mRNA

• 5' Cap Addition: Addition of a 7-methylguanosine cap to the 5' end for stability and ribosome recognition.

• 3' Poly-A Tail: Addition of a polyadenine (poly-A) tail to the 3' end for stability and export from the nucleus.

• Splicing: Removal of non-coding regions (introns) and joining of coding regions (exons) by the spliceosome.

• Export: Mature mRNA is exported to the cytosol for translation.

Alternative Splicing: Allows a single gene to code for multiple proteins by varying the combination of exons included in the final mRNA.

Translation: Protein Synthesis

Translation is the process by which ribosomes synthesize proteins using the sequence encoded in mRNA.

• Codons: Triplets of nucleotides in mRNA that specify amino acids.

• tRNA: Transfer RNA molecules bring amino acids to the ribosome, matching their anticodon to the mRNA codon.

• Ribosome Structure: Ribosomes have three binding sites for tRNA: A (aminoacyl), P (peptidyl), and E (exit).

• Translation Steps:

  1. Initiation: Ribosome assembles at the start codon (AUG).

  2. Elongation: tRNAs bring amino acids, peptide bonds form, ribosome moves along mRNA.

  3. Termination: Stop codon is reached, release factor binds, and the polypeptide is released.

Example: The codon AUG codes for methionine and serves as the start signal for translation.

Human Genetic Variation and Mutations

Genetic Variation

Humans are genetically very similar, but small differences (polymorphisms) exist and contribute to individual uniqueness.

• Single Nucleotide Polymorphisms (SNPs): Variations at a single nucleotide position in the genome.

• Mutations: Changes in DNA sequence that can be inherited or acquired.

• Types of Mutations:

  • Inherited: Passed from parent to offspring.

  • Spontaneous: Errors during DNA replication.

  • Induced: Caused by environmental factors (e.g., UV light, chemicals).

• Chromosomal Abnormalities: Include translocations, deletions, duplications, and inversions.

Example: UV light can induce mutations leading to skin cancer.

Cellular Metabolism

Metabolism Overview

Metabolism encompasses all chemical reactions in the body, divided into catabolism (breaking down molecules to release energy) and anabolism (building molecules, requiring energy).

• Catabolism: Releases energy, e.g., breakdown of glucose.

• Anabolism: Consumes energy, e.g., synthesis of proteins.

Coenzymes

• NAD+ and FAD: Electron carriers that accept and transfer electrons during metabolic reactions.

• Oxidation-Reduction (Redox) Reactions:

  • Oxidation: Loss of electrons.

  • Reduction: Gain of electrons.

Carbohydrate Metabolism

Glycolysis

Glycolysis is the anaerobic breakdown of glucose to pyruvate, producing ATP and NADH.

• Location: Cytosol of the cell.

• Steps:

  1. Phosphorylation of glucose (uses 2 ATP).

  2. Splitting of 6-carbon glucose into two 3-carbon pyruvate molecules.

  3. Generation of 4 ATP (net gain: 2 ATP) and 2 NADH.

• Products (per glucose):

  • 2 Pyruvate

  • 2 ATP (net)

  • 2 NADH

Aerobic Respiration

Aerobic respiration occurs in the mitochondria and includes the citric acid cycle and electron transport chain (ETC).

• Mitochondrial Structure:

  • Outer membrane: Permeable to ions and small molecules.

  • Inner membrane: Contains carrier proteins and the ETC.

  • Intermembrane space: Between outer and inner membranes.

The Citric Acid Cycle (Krebs Cycle)

The citric acid cycle oxidizes acetyl-CoA to CO2, generating NADH, FADH2, and GTP.

• Key Steps:

  • Acetyl-CoA combines with oxaloacetate to form citrate.

  • Series of reactions release CO2 and transfer electrons to NAD+ and FAD.

  • Produces 3 NADH, 1 FADH2, 1 GTP (converted to ATP) per cycle.

Electron Transport Chain (ETC) and ATP Synthesis

The ETC uses electrons from NADH and FADH2 to create a proton gradient across the inner mitochondrial membrane, driving ATP synthesis via ATP synthase.

• Oxygen: Final electron acceptor, forms water.

• ATP Yield: Up to 36 ATP per glucose molecule (2 from glycolysis, 2 from citric acid cycle, 32 from ETC).

The Integumentary System

Components and Functions

The integumentary system includes the skin and its accessory structures, providing protection, sensation, and regulation.

• Components:

  • Hypodermis: Subcutaneous layer of adipose and areolar connective tissue.

  • Dermis: Middle layer, contains blood vessels, nerves, glands.

  • Epidermis: Outermost epithelial layer.

• Functions:

  • Physical barrier

  • Immune defense

  • UV protection

  • Body temperature regulation

  • Synthesis of vitamin D

  • Excretion

  • Sensation

Skin Structure

• Epidermis: Stratified squamous epithelium, avascular, varies in thickness (thin skin: 0.1–0.15 mm; thick skin: 0.5–4.5 mm).

• Cell Types:

  • Keratinocytes: Most abundant, produce keratin for protection.

  • Stem cells: Located in the stratum basale, give rise to keratinocytes.

  • Melanocytes: Produce melanin pigment, also in the stratum basale.

Accessory Structures

• Sebaceous Glands: Secrete sebum (lipid mixture) for waterproofing and antimicrobial action. Blockage can cause acne.

• Sweat Glands: Involved in thermoregulation and excretion.

Regulation of Body Temperature

• Heat Loss: Via conduction, convection, radiation, and evaporation.

• Blood Flow: Vasodilation increases heat loss; vasoconstriction conserves heat.

• Neural Regulation: Hypothalamus controls sweat gland activity and blood flow to skin.

Vitamin D Synthesis and Disorders

• Vitamin D: Synthesized in skin upon UV exposure; necessary for calcium and phosphorus absorption.

• Deficiency: Can cause rickets (soft, weak bones in children).

Table: Summary of Key Metabolic Pathways

Additional info: The notes also reference the structure and function of ribosomes, tRNA, and the process of translation, as well as the importance of coenzymes in metabolism. The integumentary system section includes details on skin layers, cell types, and accessory glands, which are essential for understanding skin physiology and pathology.