---

Cell Physiology - Complete Guide

From Guyton & Hall Textbook of Medical Physiology (14th Edition)

---

1. COMPOSITION OF THE CELL (PROTOPLASM)

• Nucleus - control center (DNA, genes)
• Cytoplasm - metabolic factory (organelles)

---

2. CELL MEMBRANE (PLASMA MEMBRANE)

Structure

• Thickness: 7.5 to 10 nanometers
• Composition: 55% proteins, 25% phospholipids, 13% cholesterol, 4% other lipids, 3% carbohydrates
• Basic structure: a lipid bilayer - two layers of lipid molecules, each one molecule thick, continuous over the entire cell surface
• Large globular proteins are interspersed throughout this lipid film

Lipid Bilayer Components

1. Phospholipids - most abundant; phosphate end (hydrophilic, faces water) + fatty acid tail (hydrophobic, faces inward)
2. Sphingolipids - similar structure to phospholipids
3. Cholesterol - dissolved in the fatty portion of the lipid bilayer; regulates membrane fluidity and permeability

Membrane Proteins

• Integral (transmembrane) proteins - penetrate all the way through the bilayer; function as channels or carriers
• Peripheral proteins - attached to only one surface; often function as enzymes or structural elements

• Channel proteins - watery pores for water, ions, small molecules (selective)
• Carrier (transporter) proteins - bind specific molecules and undergo conformational changes to move them across
• Receptor proteins - bind hormones/ligands to trigger intracellular signals
• Enzymes - catalyze membrane-associated reactions
• Structural proteins - anchor cytoskeleton to membrane

---

3. CYTOPLASM AND ITS ORGANELLES

A. Endoplasmic Reticulum (ER)

• Rough ER (RER): studded with ribosomes; synthesizes proteins destined for secretion or the cell membrane
• Smooth ER (SER): no ribosomes; synthesizes lipids (including steroid hormones), detoxifies drugs, stores Ca²⁺ in muscle cells

B. Golgi Apparatus

• Works with the ER as the cell's "processing and packaging plant"
• Receives proteins from ER vesicles → modifies, concentrates, packages them → secretory vesicles bud off and are transported to the cell surface for exocytosis
• Also manufactures carbohydrates and combines them with proteins to form glycoproteins

C. Mitochondria

• The cell's "powerhouse" - generate ~95% of all ATP
• Double membrane: outer smooth membrane + inner membrane with folds called cristae
• The cristae project into the matrix and contain the ATP synthase enzymes
• Contain their own DNA (circular, maternally inherited) and ribosomes
• Can reproduce independently by splitting in two

1. Glucose → (glycolysis in cytoplasm) → Pyruvic acid → only <5% ATP from this step
2. Pyruvate → Acetyl-CoA → Krebs (citric acid) cycle in mitochondrial matrix
3. Hydrogen atoms stripped → electrons removed → hydrogen ions combine with O₂ → chemiosmotic mechanism → ATP synthase converts ADP + Pi → ATP

D. Lysosomes

• Membranous sacs containing hydrolytic (digestive) enzymes
• pH inside ~5.0 (acidic) - activates the enzymes
• Functions:
  • Digest material from phagocytosis (bacteria, dead cells)
  • Digest material from pinocytosis (extracellular fluid droplets)
  • Autophagy - digest worn-out cell organelles
• Lysosomal enzymes break down proteins, carbohydrates, lipids, nucleic acids
• Clinical relevance: Lysosomal storage diseases (e.g., Gaucher's, Tay-Sachs) result from enzyme deficiencies

E. Peroxisomes

• Similar to lysosomes but contain oxidases rather than hydrolytic enzymes
• Oxidize amino acids and fatty acids; use catalase to break down H₂O₂ → H₂O + O₂
• Abundant in liver cells (detoxification of alcohol, drugs)

F. Ribosomes

• Composed of ribosomal RNA (rRNA) + proteins
• Two subunits: large (60S) + small (40S) → together = 80S
• Site of protein translation
• Found free in cytoplasm (synthesize cytoplasmic proteins) or attached to rough ER (synthesize secreted/membrane proteins)

G. Cell Cytoskeleton

---

4. NUCLEUS

Nuclear Membrane (Nuclear Envelope)

• Two separate bilayer membranes (inner + outer)
• Outer membrane is continuous with the ER
• Contains nuclear pores - large protein complexes (~9 nm diameter) that allow selective passage of RNA, proteins, and other molecules

Nucleolus

• Dense body within the nucleus (not membrane-bound)
• Site of ribosomal RNA (rRNA) synthesis and ribosome assembly
• Prominent in cells that are actively synthesizing protein

Chromatin and Chromosomes

• DNA is wrapped around histone proteins to form nucleosomes (DNA + 8 histones = nucleosome bead)
• Nucleosomes coil further → 30-nm fiber → loops → chromosomes
• Human cells: 46 chromosomes in 23 pairs (diploid)
• ~6 feet of DNA is packed into a nucleus ~6 micrometers in diameter

---

5. TRANSPORT ACROSS THE CELL MEMBRANE

A. DIFFUSION (Passive)

1. Simple Diffusion
   • Molecules move directly through the lipid bilayer OR through protein channels
   • Rate is proportional to:
     • Concentration gradient
     • Lipid solubility (for lipid-soluble substances)
     • Molecular size (smaller = faster)
     • Cross-sectional area of membrane
   • Examples: O₂, CO₂, alcohol, steroid hormones (lipid-soluble - diffuse directly through lipid)
2. Facilitated Diffusion
   • Requires a carrier protein or channel protein
   • Still moves DOWN the concentration gradient (no energy needed)
   • Examples: Glucose transport into cells (via GLUT transporters), amino acid transport

• Osmotic pressure - pressure needed to prevent osmotic movement
• Tonicity of solutions: isotonic, hypertonic, hypotonic

Net rate ∝ (Concentration₁ - Concentration₂) × Membrane permeability

B. ACTIVE TRANSPORT (Energy-Requiring)

• Energy from direct ATP hydrolysis
• Most important example: Na⁺-K⁺-ATPase pump (Sodium-Potassium pump)
  • Pumps 3 Na⁺ OUT and 2 K⁺ IN per ATP hydrolyzed
  • Maintains: intracellular Na⁺ low (~14 mEq/L), intracellular K⁺ high (~140 mEq/L)
  • Generates the resting membrane potential
  • Electrogenic (creates net negative charge inside)
• Other examples: Ca²⁺-ATPase, H⁺-K⁺-ATPase (stomach parietal cells)

• Uses the Na⁺ gradient (created by Na⁺-K⁺-ATPase) as the energy source - no direct ATP used
• Symport (co-transport): Na⁺ and another substance move in the same direction
  • Example: Na⁺-glucose co-transporter (SGLT1) in intestinal epithelium
  • Example: Na⁺-amino acid co-transport
• Antiport (counter-transport/exchange): Na⁺ moves in, another substance moves out
  • Example: Na⁺-Ca²⁺ exchanger (NCX) in cardiac muscle
  • Example: Na⁺-H⁺ exchanger

C. ENDOCYTOSIS AND EXOCYTOSIS

• Phagocytosis ("cell eating"): ingestion of large particles (bacteria, dead cells) - mostly immune cells (macrophages, neutrophils)
  • Pseudopods flow around the particle → phagosome forms → fuses with lysosome → digestion
• Pinocytosis ("cell drinking"): ingestion of tiny droplets of extracellular fluid
  • Common in most cells
• Receptor-mediated endocytosis: highly selective; ligand binds receptor in a coated pit (clathrin-coated) → clathrin-coated vesicle forms → internalizes specific molecules (e.g., LDL cholesterol, hormones)

• Vesicles formed in ER/Golgi fuse with cell membrane → contents released outside
• Triggered by: Ca²⁺ influx, nerve signals, hormones
• Examples: secretion of hormones, neurotransmitters, digestive enzymes

---

6. MEMBRANE POTENTIALS

Resting Membrane Potential (RMP)

• Typical value in nerve/muscle: -70 to -90 mV (inside negative)
• Maintained by:
  1. Selective membrane permeability - K⁺ leaks out more than Na⁺ leaks in (through leak channels)
  2. Na⁺-K⁺-ATPase - electrogenic pump (extrudes 3 Na⁺ for every 2 K⁺ brought in)
• The Nernst equation calculates the equilibrium potential for a single ion:

  E = (61/z) × log(Co/Ci) mV

• The Goldman-Hodgkin-Katz equation accounts for all permeable ions

---

7. GENETIC CONTROL OF CELL FUNCTION

DNA Structure

• Double helix composed of two strands wound around each other
• Each strand = alternating phosphate + deoxyribose backbone with nitrogenous bases attached
• Four bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C)
• Base pairing: A-T (2 hydrogen bonds), G-C (3 hydrogen bonds) - complementary
• Antiparallel strands: one runs 5'→3', the other 3'→5'

From Gene to Protein: The Central Dogma

Step 1: Transcription (Nucleus)

• RNA polymerase unwinds DNA and reads the template strand
• Builds messenger RNA (mRNA) using RNA nucleotides (U replaces T)
• mRNA is processed: introns removed, exons spliced → mature mRNA leaves nucleus through nuclear pores
• RNA types produced:
  • mRNA (messenger) - carries genetic code to ribosome
  • tRNA (transfer) - carries amino acids; has anticodon complementary to mRNA codon
  • rRNA (ribosomal) - structural component of ribosomes
  • miRNA / siRNA - regulatory non-coding RNAs (suppress gene expression)

Step 2: Translation (Ribosomes in cytoplasm)

• mRNA threads through ribosome
• Each codon (3 nucleotides) on mRNA specifies one amino acid
• tRNA anticodon matches the mRNA codon → delivers correct amino acid
• Ribosome links amino acids via peptide bonds → polypeptide chain
• Chain released when a stop codon (UAA, UAG, UGA) is reached
• Polyribosomes: multiple ribosomes read the same mRNA simultaneously → mass production

Genetic Code

• 64 possible codons (4³ = 4 bases, 3 at a time)
• 61 code for amino acids, 3 are stop codons
• The code is degenerate (multiple codons can code for the same amino acid) but non-ambiguous (one codon codes for only one amino acid)

DNA Replication

• Semi-conservative: each new DNA molecule has one old strand + one new strand
• Key enzymes:
  • Helicase - unwinds the double helix at the replication fork
  • Primase - lays down RNA primer
  • DNA polymerase - adds new nucleotides (only works 5'→3')
  • DNA ligase - joins Okazaki fragments on the lagging strand
  • Topoisomerase - relieves tension ahead of the replication fork
• DNA proofreading: polymerase checks for errors; repair enzymes correct mismatches → mutation rate is extremely low
• A mutation = permanent alteration in the base sequence

Chromosome Organization

• DNA is wound around histone proteins → nucleosomes (beads on a string)
• Nucleosomes coil → chromatin fibers → chromosomes
• 46 chromosomes (23 pairs) in human diploid cells
• Approx. 6 feet of DNA packaged into a 6 µm nucleus

Gene Regulation

• Transcription factors (proteins) bind to specific DNA sequences (promoters/enhancers) to activate or suppress gene transcription
• Epigenetic regulation: histone modification (acetylation, methylation) controls chromatin accessibility
• miRNA/siRNA pathway: miRNAs bind to complementary mRNA sequences → prevent translation or cause mRNA degradation (RNA-induced silencing complex, RISC)
• Important: miRNA alterations are associated with cancer and heart disease

---

8. ENERGY METABOLISM - ATP

Structure of ATP

• Adenine + Ribose + 3 phosphate groups
• Last two phosphate groups are connected by high-energy bonds (~12,000 cal/mol each)
• ATP → ADP + Pi: releases energy to drive cell functions

ATP Uses in the Cell

• Muscle contraction
• Active transport (Na⁺-K⁺ pump, Ca²⁺ pump)
• Protein synthesis (ribosomes)
• DNA/RNA synthesis
• Ciliary movement
• Cell division

ATP Production

• Pyruvate → Acetyl-CoA
• Krebs Cycle → NADH + FADH₂ + CO₂
• Electron transport chain → H⁺ gradient across inner mitochondrial membrane
• ATP synthase uses H⁺ gradient (chemiosmosis) → ATP

---

9. CELL REPRODUCTION - CELL CYCLE AND MITOSIS

Cell Cycle Phases

Mitosis Stages

1. Prophase - chromosomes condense; mitotic spindle begins to form from centrioles
2. Metaphase - chromosomes align at the metaphase plate (cell equator); spindle fibers attach to centromeres
3. Anaphase - sister chromatids pulled to opposite poles by microtubules
4. Telophase - nuclear envelope reforms around each set; chromosomes decondense
5. Cytokinesis - cytoplasm divides → two daughter cells

Control of Cell Division

• Cyclins and cyclin-dependent kinases (CDKs) regulate cell cycle checkpoints
• Checkpoints: G₁/S (DNA integrity check), G₂/M (DNA replication complete?), spindle checkpoint (chromosomes attached properly?)
• Proto-oncogenes → stimulate division; when mutated become oncogenes (cancer)
• Tumor suppressor genes (e.g., p53, Rb) → inhibit division; loss of function → cancer

Meiosis (for context)

• Only in reproductive cells
• Two divisions → 4 cells with 23 chromosomes each (haploid)
• Crossing over in meiosis I increases genetic diversity

---

10. CELL LOCOMOTION

• Amoeboid movement (pseudopods): actin polymerization at the leading edge pushes the membrane forward (e.g., macrophages, white blood cells)
• Cilia and flagella: structures containing a 9+2 arrangement of microtubules (9 peripheral doublets + 2 central singlets); powered by dynein ATPase; coordinated beating moves fluid (cilia in airways) or propels the cell (sperm flagellum)

---

Summary: Key Numbers to Remember (MBBS Exam)

---