Comprehensive Study Notes: Molecular Interactions, Cellular Metabolism, Membrane Dynamics, Endocrine, Nervous, Sensory, Blood, and Respiratory Physiology

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Protein Structure and Function

Levels of Protein Structure

Proteins are complex molecules essential for structure and function in living organisms. Their function is determined by their structure, which is organized into four hierarchical levels:

Primary Structure: The linear sequence of amino acids in a polypeptide chain, held together by peptide bonds.
Secondary Structure: Local folding patterns such as α-helix and β-pleated sheet, stabilized by hydrogen bonds between backbone atoms.
Tertiary Structure: The three-dimensional folding of a single polypeptide, maintained by disulfide bonds, hydrogen bonds, ionic bonds, and hydrophobic interactions.
Quaternary Structure: The assembly of multiple polypeptide subunits into a functional protein complex (e.g., hemoglobin, potassium channels).

Protein Activation: Proteins may require activation by proteolytic cleavage or binding of cofactors/ligands. For example, trypsinogen is an inactive precursor of trypsin.

Ligand: Any molecule or ion that binds to a protein, often to regulate its function (e.g., opening a channel).

Atoms, Ions, and Chemical Bonds

Atomic Structure and Ions

Protons: Positively charged particles in the nucleus.
Neutrons: Neutral particles in the nucleus.
Electrons: Negatively charged particles in orbitals/shells around the nucleus.
Ions: Atoms that have gained or lost electrons. Cations are positive (e.g., Na+, K+), Anions are negative (e.g., Cl-).

Chemical Bonds

Ionic Bonds: Formed when one atom donates an electron to another, creating oppositely charged ions that attract.
Covalent Bonds: Atoms share electrons to achieve stability.
Hydrogen Bonds: Weak attractions between polar molecules, important in DNA base pairing and water properties.

pH, Acids, Bases, and Buffers

pH Scale and Buffer Systems

pH: Measures hydrogen ion concentration. pH < 7 is acidic, pH = 7 is neutral, pH > 7 is basic (alkaline).
Acids: Release H+ ions (e.g., HCl).
Bases: Accept H+ ions or release OH-.
Bicarbonate Buffer System: Maintains blood pH. The key equation is:
Exercise and pH: Intense exercise increases lactate and H+, lowering pH (acidosis).

Carbohydrates, Lipids, and Nucleic Acids

Carbohydrates

Composed of monosaccharides (simple sugars).
Polysaccharides: Long chains of sugars (e.g., glycogen in animals).
Glucose: Primary molecule for ATP production.

Lipids

Include triglycerides, steroids, cholesterol, and phospholipids (with head and tail regions).

Nucleic Acids and Nucleotides

Made of nucleotides, each with a five-carbon sugar, phosphate group, and nitrogenous base.
DNA: Contains deoxyribose; RNA: Contains ribose.
Base Pairing: Cytosine pairs with guanine.
ATP: Main energy-transfer molecule.
Functions: Energy transfer, genetic information, signaling (e.g., cAMP).

Enzymes and Cellular Metabolism

Enzyme Structure and Function

Enzymes are protein catalysts that speed up chemical reactions by lowering activation energy.
They have specific binding sites for substrates, forming enzyme-substrate complexes.
Cofactors: Non-protein helpers (e.g., calcium) required for enzyme activity.
Inhibition: Competitive inhibitors block the active site; Noncompetitive inhibitors bind elsewhere, altering enzyme shape.
Enzymes can be denatured by heat or pH changes.

Types of Enzymes

Hydrolases: Catalyze hydrolysis reactions (add/subtract water).
ATP Synthase: Generates ATP using H+ gradient in the electron transport chain (ETC).

Cellular Respiration Pathways

Glycolysis: Occurs in cytosol; breaks glucose into pyruvate.
Intermediate Step: Pyruvate to acetyl-CoA in mitochondrial matrix.
Krebs Cycle (Citric Acid Cycle): In mitochondrial matrix; produces NADH, FADH2, and CO2.
Electron Transport Chain (ETC): On inner mitochondrial membrane; uses oxygen as final electron acceptor.

Overall ATP Production Equation:

Red blood cells lack mitochondria and rely solely on glycolysis for ATP.
Low oxygen (hypoxia) leads to lactic acid production from pyruvate.
During starvation, fats are broken down first (lipolysis), then proteins (gluconeogenesis).

Membrane Dynamics and Transport

Fluid Compartments and Membrane Transport

Extracellular Fluid (ECF): Includes interstitial fluid and plasma.
Simple Diffusion: Passive movement of small, nonpolar molecules (e.g., O2, CO2) across the membrane.
Osmosis: Passive movement of water from low to high solute concentration.
Facilitated Diffusion: Passive, uses membrane proteins; no ATP required.
Active Transport: Requires ATP to move substances against their gradient (e.g., Na+/K+ pump).
Exocytosis: Vesicular transport of large molecules out of the cell using ATP.

Resting Membrane Potential

Typical value: –70 mV in neurons.
Maintained by Na+/K+ pump (3 Na+ out, 2 K+ in) and K+ leak channels.
ECF is high in Na+, Cl-, and HCO3-.

Osmolarity and Tonicity

Hypotonic Solution: Lower solute concentration than cell; water enters cell, causing swelling.
Permeability: Determined by membrane composition and presence of channels/carriers.

Endocrine System and Hormone Regulation

Hormone Pathways and Functions

Calcium Balance: Regulated by PTH (raises Ca2+), calcitonin (lowers Ca2+), and calcitriol (increases absorption).
Thyroid Hormone: Controlled by TSH from anterior pituitary; TSH is stimulated by TRH from hypothalamus.
Posterior Pituitary: Stores and releases oxytocin and ADH (produced in hypothalamus).
RAAS Pathway: Renin (kidney) → angiotensinogen (liver) → angiotensin I → ACE (lung) → angiotensin II → aldosterone (adrenal cortex).
Prolactin: Stimulates milk production; Oxytocin: Stimulates milk ejection and uterine contractions.
ACTH: Stimulates adrenal cortex to release cortisol.
Parathyroid Hormone: Acts on bone, kidney, and intestine to raise blood calcium.
Renin: Initiates RAAS, increasing blood pressure and sodium retention.
Thyroid Peroxidase: Enzyme for thyroid hormone synthesis (iodination and coupling).
Aldosterone: Increases sodium reabsorption and potassium excretion in kidneys.
Insulin and Glucagon: Regulate blood glucose (insulin lowers, glucagon raises).

Nervous System: Neurons and Glia

Neuronal Structure and Function

Microglia: Act as immune cells in the CNS.
Myelin: Produced by Schwann cells (PNS) and oligodendrocytes (CNS); increases conduction speed via saltatory conduction.
Action Potentials: Begin at axon hillock; involve rapid Na+ influx (depolarization) and K+ efflux (repolarization).
Absolute Refractory Period: No new action potential can be generated.
Graded Potentials: Local changes in membrane potential; can summate to trigger action potentials.
All-or-None Principle: Action potentials fire fully or not at all.
Neurotransmitter Release: Triggered by Ca2+ influx at axon terminal; released by exocytosis.
Excitatory Neurotransmitters: Depolarize postsynaptic membrane (e.g., open Na+ channels).
Inhibitory Neurotransmitters: Hyperpolarize postsynaptic membrane (e.g., open K+ or Cl- channels).

Central Nervous System: Brain Anatomy and Physiology

Brain Protection and Function

Protected by meninges, skull, and cerebrospinal fluid (CSF).
Consumes ~50% of body glucose; requires constant oxygen supply.
Corpus Callosum: Connects cerebral hemispheres.
Dorsal Root Ganglia: House sensory neuron cell bodies.
Choroid Plexus: Secretes CSF.
Medulla Oblongata: Controls vital autonomic functions.
Reticular Formation: Regulates arousal and sleep-wake cycles.
Vagus Nerve (CN X): Mixed cranial nerve for internal organs.
Hypothalamus: Key center for homeostasis and hormone regulation.
Suprachiasmatic Nucleus (SCN): Internal clock for circadian rhythms.
Hippocampus: Essential for learning and memory.
Amygdala: Center for emotions.
Epinephrine: Released during fight-or-flight response.

Sensory Physiology: Special Senses

General Sensory Pathways

All sensory pathways (except olfaction) relay through the thalamus.
Nociceptors: Detect pain; Chemoreceptors: Detect chemicals; Mechanoreceptors: Detect pressure/vibration; Thermoreceptors: Detect temperature.

Hearing and Equilibrium

Middle ear bones (malleus, incus, stapes) amplify sound.
Sound waves → tympanic membrane → vibrations → cochlea.
Hair cells in cochlea transduce vibrations; highest frequencies detected at cochlear base.
Semicircular canals detect rotational acceleration; utricle and saccule detect linear acceleration.

Vision

Light enters through pupil; lens shape controlled by ciliary muscle.
Fovea: Area of sharpest vision.
Retinal pigment (retinal) derived from vitamin A.
Blind spot: Where optic nerve exits retina.

Taste and Smell

Five primary tastes: sweet, salty, sour, bitter, umami.

Metabolism and Energy Balance

Glucose and Lipid Metabolism

Glucose stored as glycogen in liver and muscle.
Gluconeogenesis: Synthesis of glucose from noncarbohydrate sources.
Lipolysis: Breakdown of fats into glycerol and fatty acids.
Beta-oxidation: Fatty acids → Acetyl-CoA; Ketogenesis: Acetyl-CoA → ketone bodies.
During fasting/starvation, body shifts to fat and ketone metabolism.

Pancreatic Hormones

Alpha cells: Secrete glucagon (raises blood glucose).
Beta cells: Secrete insulin (lowers blood glucose).
D cells: Secrete somatostatin (regulates digestion).

Diabetes and Metabolic Effects

Insulin deficiency → high blood glucose, increased fat metabolism, risk of ketoacidosis.
Fat is the most energy-dense storage molecule.

Blood and Hematopoiesis

Red Blood Cells and Hemoglobin

Transport O2 and CO2; contain hemoglobin (four globin chains, each with heme and iron).
Produced in red bone marrow, stimulated by erythropoietin (EPO) from kidneys.
Lifespan ~120 days; removed by spleen/liver.
Hematocrit: % of blood volume occupied by RBCs.

Plasma and Proteins

Plasma is ~90% water; main proteins: albumin, globulins, fibrinogen.
Iron transported by transferrin; stored as ferritin.

Platelets and Coagulation

Platelets form plugs and release clotting factors.
Coagulation cascade: Intrinsic (collagen exposure) and extrinsic (tissue factor) pathways converge to form fibrin clot.
Fibrinolysis breaks down clots after repair.

Laboratory Tests

Prothrombin Time (PT): Assesses extrinsic pathway (factor VII).

Respiratory System: Mechanics and Gas Exchange

Alveoli and Gas Exchange

Type II Alveolar Cells: Produce surfactant to reduce surface tension and prevent alveolar collapse.
Alveoli are the primary sites of O2 and CO2 exchange.

Ventilation Mechanics

Inhalation: Diaphragm and external intercostals contract, increasing thoracic volume and decreasing pressure.
Exhalation: Muscles relax, thoracic volume decreases, pressure increases, air flows out.
Air moves from high to low pressure.

Pulmonary Volumes

Volume	Description
Tidal Volume (TV)	Normal breath volume
Inspiratory Reserve Volume (IRV)	Extra air inhaled after normal inhalation
Expiratory Reserve Volume (ERV)	Extra air exhaled after normal exhalation
Residual Volume (RV)	Air remaining after maximal exhalation
Vital Capacity (VC)	Total air exhaled after maximal inhalation
Total Lung Capacity (TLC)	Maximum lung volume
Functional Residual Capacity (FRC)	Air left after normal exhalation

Oxygen and Carbon Dioxide Transport

O2 mostly carried by hemoglobin; CO2 mostly as bicarbonate (HCO3-).
O2-hemoglobin dissociation curve shifts right with increased CO2, temperature, or decreased pH (Bohr effect).
CO2 also binds hemoglobin (carbaminohemoglobin) or dissolves in plasma.

Acid-Base Balance

Hyperventilation causes respiratory alkalosis (CO2 loss).
Kidneys compensate by excreting bicarbonate.
Increased CO2 stimulates ventilation to restore balance.

Surfactant

Reduces alveolar surface tension, preventing collapse and easing breathing.