Cell Structure: Prokaryotic vs Eukaryotic Cells

Structure of Cells

• Prokaryotic cells lack a nucleus and membrane-bound organelles. Their DNA is circular, and they have smaller ribosomes (70S).
• Eukaryotic cells possess a true nucleus, membrane-bound organelles, and are typically larger in size compared to prokaryotic cells.
• The cell membrane comprises a phospholipid bilayer with hydrophilic heads and hydrophobic tails, along with integral and peripheral proteins and cholesterol, which contributes to membrane fluidity.
• Mitochondria synthesize ATP through oxidative phosphorylation, regulate apoptosis, have a double membrane, and their DNA is maternally inherited.
• The nucleus stores DNA, regulates transcription, and contains nuclear pores that control the movement of substances in and out.
• The rough ER is involved in protein synthesis for secretion or membrane integration and is characterized by the presence of ribosomes.
• The smooth ER is responsible for lipid synthesis, detoxification processes, and calcium storage.
• The Golgi apparatus modifies proteins post-translationally, sorts them, and facilitates vesicular trafficking.
• Lysosomes contain hydrolytic enzymes and are involved in autophagy and phagocytosis.
• Peroxisomes facilitate fatty acid beta-oxidation and hydrogen peroxide detoxification.
• Microtubules, made of tubulin polymers, form the spindle during mitosis and act as vesicle transport pathways.
• Intermediate filaments provide structural integrity and mechanical support to cells, with keratins being an example.
• Microfilaments, composed of actin, are involved in cell migration and muscle contraction through polymerization and depolymerization.

Matrix, Motors, and Movement

• Collagen provides tensile strength to the extracellular matrix (ECM) due to its triple helix structure.
• Elastin contributes to tissue elasticity within the ECM.
• Proteoglycans in the ECM help retain water and provide cushioning.
• Integrins facilitate cell adhesion and signal transduction within the ECM.
• Kinesin motor proteins transport cargo toward the plus end of microtubules, away from the nucleus.
• Dynein motor proteins are involved in retrograde transport and facilitate ciliary and flagellar beating.
• Myosin motor proteins use ATP to slide actin filaments in muscles, enabling muscle contraction.

Cell Signaling and Movement

• G protein-coupled receptors (GPCRs) activate different pathways, including Gαs/cAMP, Gαq/IP3/DAG/Ca2+, and Gαi inhibitory pathways.
• Receptor tyrosine kinases (RTKs) activate the MAP kinase cascade and PI3K-AKT pathway.
• Steroid hormones bind to intracellular receptors and regulate gene transcription.
• Secondary messengers like cAMP, IP3, DAG, and Ca2+ amplify signaling pathways.
• Cell migration involves chemotaxis and lamellipodia formation, with actin polymerization regulated by Rac, Rho, and CDC42.

Pharmacology: Absorption, Distribution, Metabolism, Excretion (ADME)

• Absorption involves bioavailability and is influenced by first-pass metabolism and the route of administration (oral vs. IV).
• Distribution is affected by lipophilicity, tissue perfusion, plasma protein binding, and the blood-brain barrier.
• Metabolism occurs in two phases: Phase I involving CYP450 oxidation and Phase II involving conjugation, glucuronidation, and acetylation.
• Excretion involves renal clearance mechanisms (glomerular filtration, tubular secretion) and hepatic clearance.

Glucose and Energy Metabolism

• Key enzymes in glycolysis include hexokinase, phosphofructokinase-1, and pyruvate kinase, which are also regulation points.
• Rate-limiting enzymes in the TCA cycle are citrate synthase and α-ketoglutarate dehydrogenase.
• The electron transport chain involves Complexes I-IV, ATP synthase, and oxygen, which acts as the final electron acceptor.
• Insulin and glucagon regulate glycogenesis, glycogenolysis, and gluconeogenesis.

Lipid Metabolism and Dyslipidemias

• Fatty acid metabolism involves detailed beta-oxidation steps and is regulated by insulin and glucagon.
• Cholesterol metabolism includes cholesterol synthesis, with HMG-CoA reductase as a key enzyme, and the functions of LDL and HDL.
• Dyslipidemias include familial hypercholesterolemia and are linked to clinical correlations such as atherosclerosis risk.

Protein Metabolism

• Amino acid catabolism involves transamination, using ALT/AST enzymes, and the urea cycle, where ornithine transcarbamylase deficiency can occur.
• Nitrogen balance has clinical significance in nutritional assessment.
• Metabolic integration considers the fed vs. fasting state, including gluconeogenesis substrates during fasting.

Nucleic Acids

• DNA replication is semi-conservative and involves helicase, primase, and DNA polymerase proofreading.
• Transcription involves promoters, enhancers, transcription factors, and RNA splicing.
• Translation involves codon-anticodon pairing, elongation factors, and ribosome structure.

Carcinogenesis and Cancer Genetics

• Tumor biology includes p53 mutations, oncogenic signaling (RAS/MAPK pathway), apoptosis evasion, and limitless replication potential.
• Metastasis mechanisms involve EMT (epithelial-mesenchymal transition), angiogenesis factors (VEGF), invasion of the basement membrane, and the tumor microenvironment.

Immunology: Innate Immunity

• Macrophages, neutrophils, dendritic cells, and NK cells are key cell types in innate immunity.
• The inflammatory response involves cytokines (IL-1, IL-6, TNFα), the complement system, and pathogen recognition by PRRs (TLRs). It can be acute or chronic, with inflammatory mediators such as histamines, prostaglandins, and leukotrienes.

Adaptive Immunity

• T/B cell activation involves MHC molecules, co-stimulatory signals, cytokine roles, clonal selection, and antigen presentation by APCs.
• Antibody functions include neutralization, opsonization, complement activation, class switching, and affinity maturation.

Infectious Diseases

• Bacterial pathogenesis involves adhesins, toxins (endotoxin/LPS vs. exotoxins), biofilms, and antibiotic resistance mechanisms.
• The viral life cycle includes attachment, entry, replication, and release mechanisms, as well as viral latency and host immune evasion.
• Fungal/parasitic infections have distinct clinical features and are treated with antifungal drugs (azoles, polyenes) and antiparasitic drugs (antimalarials, antihelminthics).

Introduction to Pathology

• Cell injury includes apoptosis (caspase activation) and necrosis patterns (coagulative, liquefactive, caseous, fibrinoid, fat necrosis), as well as ischemia-reperfusion injury.
• Inflammation involves mediators (histamine, cytokines), outcomes (resolution, chronic inflammation, fibrosis), granulomatous inflammation, and hypersensitivity reactions (Type I-IV).