Gene Expression and Protein Synthesis

Gene Expression

• DNA contains nucleotides which are composed of a base, sugar and phosphodiester linkage
• DNA is read from 5' to 3'
• RNA polymerase binds nucleotides to the antisense strand of DNA during transcription
• A 5' cap protects mRNA from degradation during transcription
• A poly A tail protects mRNA from cytosolic enzymes during transcription
• The genome is the entire DNA in a cell
• The exome is the coding portion of a genome
• An organism's complexity is related to the number of protein-coding genes and the number of genes involved in communication
• The microbiome is larger than the genome
• Gene expression is controlled most importantly through the initiation of transcription
• Euchromatin is loose and transcriptionally permissive
• Heterochromatin is condensed and less permissive for transcription
• Histone acetylation promotes transcription
• DNA methylation inhibits transcription

Proteins

• The proteome is the full compliment of proteins that can be expressed by a cell
• Protein sequences are written from the amino (N) terminus to the carboxy (C) terminus
• There are 20 amino acids specified by three base codons
• The genetic code is degenerate
• Initiation of protein translation begins with the codon AUG

Protein Trafficking

• Proteins are trafficked from the nucleus to the cytoplasm for translation
• Proteins are transported via vesicles budding off the endoplasmic reticulum to the Golgi apparatus
• The Golgi apparatus sorts and adds carbohydrates chains to proteins
• Proteins are then targeted to lysosomes and secretory vesicles
• Secretory vesicles exocytose protein

Metabolic Biochem

• Anabolic pathways break down macromolecules (oxidation) and produce energy
• Catabolic pathways build molecules (reduction)
• Every metabolic pathway has a committed step which is highly exergonic and irreversible
• Accumulation or decrease of metabolites can be used as biomarkers for disease

Glucose Metabolism

• Glycogen is a branched polymer of glucose in the cytosol
• Glycogen serves as a short term storage form of cellular energy
• Glycogen is stored in the liver (control blood glucose) and muscles (for energy)
• Insulin promotes glycogenesis (glucose to glycogen)
• Glucagon promotes glycogenolysis (glycogen to glucose)
• Glycolysis is the breakdown of glucose to pyruvate and produces ATP
• Glycolysis is the only metabolic pathway for ATP production outside the mitochondria
• The Krebs cycle produces up to 32 ATP per glucose molecule oxidized
• Gluconeogenesis primarily occurs in the liver to replenish blood glucose during prolonged fasting
• The liver can use pyruvate, lactate, glycerol and some amino acids to make glucose
• Insulin promotes glycolysis
• Glucagon promotes gluconeogenesis

Absorptive/Post-Absorptive States

• The absorptive state promotes anabolic pathways
• The post-absorptive state promotes catabolic pathways

Type I Diabetes

• Type I diabetes leads to hyperglycemia, hypertriglycerolemia and ketoacidosis

Signal Transduction and Cell Fate

• Signal transduction pathways involve a series of events that occur when a cell receives a signal from its environment
• Signal transduction pathways involve protein kinases and phosphatases
• Signal transduction pathways are crucial for cell growth, division and death

Anatomy

• The patella is the kneecap

• The popliteus is a muscle located on the back of the knee

• The calf muscle is located on the back of the lower leg

• The crus refers to the leg

• The tarsus refers to the ankle

• The median plane refers to the midline of the body

• Medial refers to structures closer to the midline

• Lateral refers to structures farther from the midline

• Superior refers to structures closer to the head

• Inferior refers to structures closer to the feet### Anatomical Terminology

• Proximal: Near a reference point.

• Distal: Away from a reference point.

• Superior: Above a reference point.

• Inferior: Below a reference point.

• Medial: towards the midline of the body.

• Lateral: away from the midline of the body.

• Superficial: Closer to the surface.

• Deep: Farther from the surface.

• Anterior: Front.

• Posterior: Back.

• Dorsal: Back or top.

• Ventral: Front or bottom.

• Cranial: Towards the head.

• Caudal: Towards the tail.

Body Planes

• Median Plane (Mid-Sagittal Plane): Divides the body into equal right and left halves.
• Sagittal Plane: Divides the body into unequal right and left halves.
• Frontal (Coronal) Plane: Divides the body into equal or unequal anterior and posterior parts.
• Transverse Plane: Divides the body into equal or unequal superior and inferior parts (cross sections).

Epithelial Tissue

• Epithelial cells are closely packed with very little extracellular matrix.
• Functions: Covering, lining, protecting surfaces; absorption; secretion.
• Types: Simple, stratified, glandular
• Shapes: Squamous, cuboidal, columnar.
• Polarity: Apical (top) and basal (bottom).
• Adhesion: Tight junctions, adhesion junctions.

Basic Connective Tissue

• Cells:
  • Fibroblasts (synthesize ECM)
  • Adipocytes (store fat)
  • Macrophages (ECM turnover)
  • Mast cells (inflammatory/immune response)
  • Plasma cells (produce antibodies)
  • Other leukocytes (in inflammatory response)
• Fibers:
  • Collagen fibers (structural proteins)
  • Reticular fibers (very thin, delicate collagen III fibers)
  • Elastic fibers (elastin and fibrillin proteins)
• Ground substance:
  • Glycosaminoglycans (GAGs)
  • Proteoglycans (proteins + GAGs)
  • Glycoproteins (proteins + carbohydrates)

Specialized Connective Tissue

Cartilage

• All cartilage contains chondrocyte cells, but the extracellular matrix differs.
• Types:
  • Hyaline (collagen II, proteoglycans, chondronectin)
  • Elastic (collagen II, elastic fibers)
  • Fibrocartilage (collagen I, collagen II)

Bone

• Cells:
  • Osteoprogenitors: precursor cells
  • Osteoblasts: synthesize bone matrix
  • Osteocytes: mature bone cells
  • Osteoclasts: resorb bone matrix
• Extracellular matrix: Collagen I, proteoglycans, glycoproteins.

Clinical Correlations Related to Bone

• Paget's disease: Uncontrolled osteoclast/osteoblast activity leading to large, disorganized bones.
• Osteoporosis: Osteoclast resorption exceeds osteoblast deposition (bone fractures).
• Rickets: Insufficient calcium.
• Scurvy: Vitamin C deficiency.

Muscle Tissue

• Structure: Epimysium > Perimysium > Endomysium.

Skeletal Muscle

• Structure: Groups of thick (myosin) and thin (actin) myofilaments.
• Characteristics:
  • Multinucleated with satellite cells.
  • Striated

Cardiac Muscle

• Structure: Cell to cell attachment via intercalated discs forming cardiac muscle fibers.
• Characteristics:
  • Centrally located nuclei.
  • Striated.

Smooth Muscle

• Structure: Fusiform cells (no striations).
• Characteristics:
  • Centrally located nucleus.

Nervous Tissue

• Cells:
  • Neurons: Motor, sensory, interneurons
  • Glia (CNS):
    • Oligodendrocytes (form myelin sheaths)
    • Astrocytes (support)
    • Microglia (immune defense, phagocytosis)
    • Ependymal cells (line ventricles and central canal)
  • Supporting Cells (PNS):
    • Schwann cells (form myelin sheaths)
    • Satellite cells (found in sensory cranial ganglia and autonomic spinal ganglia)

Embryonic Development

• Week 1:
  • Fertilization of the egg by sperm.