Molecular Basis of Physiology

Define homeostasis

A self-regulating process in which the body maintains a stable internal environment within a narrow range of physiological conditions despite external or internal changes.

What causes homeostatic imbalance?

Aging, genetic mutations, pathogens, or environmental factors → leads to disease.

Differentiate between negative and positive feedback.

-Negative feedback: Reverses a change to restore balance (most common).

-Positive feedback: Amplifies a change until stopped (e.g., childbirth, blood clotting).

Why does homeostasis require energy?

Cells need ATP to maintain structure, grow, divide, transport substances, and adapt. Without energy, cells die instantly.

List the major roles of proteins in physiology.

Catalysis (enzymes), reaction coupling (muscle contraction), transport (carriers), structural (cytoskeleton), signaling (receptors).

What determines protein function?

Substrate specificity at the active site.

Name ways protein function can be regulated (allosteric changes).

Ligand binding, covalent modifications (phosphorylation, hydroxylation, glycosylation), voltage changes, and mechanical forces.

Define a receptor and ligand.

-Receptor = protein that receives a chemical signal

-Ligand = molecule that binds to receptor to trigger downstream signaling

Name the four forms of cell-cell signaling.

Autocrine, paracrine, endocrine, and synaptic (neural).

Differentiate between cell-surface and intracellular receptors.

-Cell-surface: For hydrophilic ligands (ionotropic, GPCRs, enzyme-coupled).

-Intracellular: For hydrophobic ligands (steroid, thyroid hormones, vitamin D).

What are ionotropic receptors? Provide an example.

Ligand-gated ion channels that open when neurotransmitters bind. Example: Nicotinic acetylcholine receptor.

How do GPCRs work?

Ligand binding activates G-protein → α-subunit binds GTP → activates enzymes/ion channels → GTP hydrolyzed to GDP → resets system.

Give examples of ligands that act on GPCRs.

Neurotransmitters (epinephrine, dopamine), hormones (angiotensin, gastrin), olfactory stimuli, opioids.

Name the main GPCR second messengers.

cAMP, IP₃, DAG, and Ca²⁺.\

Give examples of messenger molecules using cAMP as a second messenger.

ADH, dopamine, glucagon, epinephrine, norepinephrine, acetylcholine.

Give examples of messenger molecules using DAG/IP₃.

Acetylcholine, epinephrine, CCK, gastrin, oxytocin.

What enzyme deactivates cAMP?

Phosphodiesterase (PDE).

Give examples of receptor tyrosine kinase ligands.

Epidermal growth factor (EGF), insulin, IGF-1, VEGF.

How do intracellular receptors work?

Lipid-soluble messengers (steroids, vitamin D, thyroid hormones) cross the membrane → bind to receptors in cytosol/nucleus → attach to hormone-response elements (HREs) in DNA → regulate gene transcription.

What are the main components of the plasma membrane?

Lipids (phospholipids, glycolipids, cholesterol), proteins (integral, peripheral), carbohydrates, water, divalent cations.

What determines membrane permeability?

Size and polarity: small, nonpolar molecules cross easily; polar molecules need transporters.

Differentiate between channels and carriers.

-Channels: Form pores for ions/water; weak solute interaction.

-Carriers: Undergo conformational changes; strong substrate interaction.

What are aquaporins?

Specialized water channels expressed in kidney and glandular cells for efficient water movement.

Define passive transport. Provide examples.

Movement down gradient, no energy (diffusion, facilitated diffusion, ion channels).

Define active transport. Provide examples.

Requires energy, moves against gradient.

-Primary: Uses ATP (e.g., Na⁺/K⁺ ATPase).

-Secondary: Uses gradients from primary transporters (e.g., Na⁺/glucose cotransporter).

-Tertiary: Driven by gradients generated from secondary transport.

Describe Na⁺/K⁺ ATPase function.

Pumps 3 Na⁺ out, 2 K⁺ in per ATP; electrogenic pump that maintains resting potential.

How is glucose absorbed in intestinal epithelium?

By Na⁺/glucose symporter (SGLT, secondary active transport) and GLUT transporter (facilitated diffusion).

Differentiate between types of endocytosis.

-Phagocytosis: Engulfing large particles.

-Pinocytosis: Engulfing fluids/small molecules.

-Receptor-mediated: Specific ligand-receptor binding triggers vesicle formation.

Differentiate between constitutive and regulated exocytosis.

-Constitutive: Continuous, no signal needed (e.g., extracellular matrix proteins).

-Regulated: Requires signal (e.g., neurotransmitter, hormone release).

What are Starling forces?

Hydrostatic and oncotic pressures that regulate filtration/reabsorption across capillary walls

At which end of the capillary does filtration vs. reabsorption dominate?

-Filtration: Arteriolar end (Pc > oncotic pressure).

-Reabsorption: Venous end (oncotic > Pc).

What happens if filtration > reabsorption?

Tissue fluid accumulates → edema.

Define resting membrane potential (RMP).

The voltage across the cell membrane in an unstimulated cell, typically -70 to -90 mV.

What are the key players in establishing RMP?

Na⁺/K⁺ ATPase, K⁺ leak channels, negatively charged proteins inside the cell.

Why is the inside of the cell negative compared to outside?

Excess of K⁺ efflux through leak channels + trapped anionic proteins → net negative charge inside.