Lecture #3

Cell Structure and Function II

Overview

This lecture focuses on advanced aspects of cell biology, including protein synthesis, membrane trafficking, and the extracellular matrix (ECM). These processes are fundamental to cellular function, tissue organization, and overall physiology.

Protein Synthesis

DNA Structure and Function

DNA (deoxyribonucleic acid) is the molecule that stores genetic information in cells. It consists of two strands forming a double helix, with each strand composed of nucleotides.

• Nucleotides are the building blocks of DNA, each containing a phosphate group, a deoxyribose sugar, and a nitrogenous base.

• DNA Bases: There are four types:

  • Purines: Adenine (A) and Guanine (G)

  • Pyrimidines: Thymine (T) and Cytosine (C)

• Base Pairing: Adenine pairs with Thymine, and Guanine pairs with Cytosine via hydrogen bonds.

• Genetic Information: Human DNA contains approximately 3 billion base pairs and encodes ~25,000 proteins.

Example: The double helix structure allows for accurate replication and transmission of genetic information during cell division.

Nucleotide Polymerization

Nucleotides are joined together by phosphodiester bonds through dehydration reactions, forming long chains (polynucleotides).

• Dehydration Reaction: Two dehydration reactions are required to form a nucleotide chain.

• Structure: Each nucleotide consists of a phosphate group, a sugar (deoxyribose in DNA), and a nitrogenous base.

Equation:

$\text{Nucleotide}_n + \text{Nucleotide}_m \xrightarrow{\text{dehydration}} \text{Polynucleotide}$

Transcription and Translation

Protein synthesis involves two main steps: transcription and translation.

• Transcription: The process by which RNA is synthesized from a DNA template. RNA polymerase binds to the promoter region and initiates mRNA synthesis.

• Translation: Ribosomes read the mRNA sequence and synthesize proteins by linking amino acids in the order specified by the mRNA.

• Ribosomes: Composed of ribosomal RNA (rRNA) and proteins; can be free in the cytoplasm or attached to the rough endoplasmic reticulum (RER).

• Protein Synthesis in RER: Produces integral membrane proteins, secreted proteins, and some organelle-specific proteins (e.g., hydrolytic enzymes in lysosomes).

Example: Insulin is synthesized in the RER and secreted by pancreatic beta cells.

Membrane Trafficking

Vesicular Transport

Cells use vesicles to transport proteins and other molecules between organelles and to the cell surface.

• Exocytosis: The process by which vesicles fuse with the plasma membrane to release their contents outside the cell.

• Endocytosis: The process by which cells engulf external substances, forming vesicles that bring materials into the cell.

• Types of Endocytosis:

  • Pinocytosis: Uptake of fluids and small molecules.

  • Phagocytosis: Engulfment of large particles or cells.

  • Receptor-mediated endocytosis: Specific uptake of molecules via receptor binding.

  • Transcytosis: Transport of substances across a cell, involving both endocytosis and exocytosis.

• Protein Coats: Vesicles are often coated with proteins (e.g., clathrin) that help shape the vesicle and select cargo.

Example: Neurotransmitter release at the synaptic cleft involves exocytosis of vesicles from the axon terminal.

Membrane Protein Trafficking

Membrane proteins are synthesized in the RER, processed in the Golgi apparatus, and transported to their final destinations via vesicles.

• SNARE Proteins: Mediate vesicle fusion with target membranes.

• Golgi Apparatus: Modifies, sorts, and packages proteins for secretion or delivery to organelles.

• Vesicle Budding: Proteins are packaged into vesicles that bud off from the RER and Golgi.

Example: Lysosomal enzymes are synthesized in the RER, modified in the Golgi, and delivered to lysosomes via vesicular transport.

Extracellular Matrix (ECM)

ECM Composition and Function

The extracellular matrix is a network of proteins and polysaccharides outside cells that provides structural support and regulates cell behavior.

• Major ECM Proteins:

  • Collagen: Most abundant protein in the human body; provides tensile strength.

  • Elastin: Provides elasticity to tissues.

  • Proteoglycans: Proteins with attached glycosaminoglycans (GAGs); contribute to matrix hydration and resilience.

• Glycosaminoglycans (GAGs): Long, negatively charged polysaccharides such as chondroitin sulfate, keratan sulfate, and hyaluronic acid.

• Function: ECM supports cells, facilitates cell signaling, and influences tissue repair.

Example: Cartilage ECM is rich in collagen and proteoglycans, providing resistance to compression.

Collagen Synthesis and Crosslinking

Collagen is synthesized by fibroblasts and undergoes post-translational modifications for stability and function.

• Vitamin C: Required for proper collagen synthesis; deficiency leads to scurvy (weak collagen, bleeding gums, poor wound healing).

• Copper: Required for lysyl oxidase activity, which crosslinks collagen fibers for strength.

• Collagen Crosslinking: Covalent bonds between collagen molecules increase tissue strength.

Equation:

$\text{Collagen} + \text{Lysyl oxidase} \xrightarrow{\text{Copper}} \text{Crosslinked collagen}$

Connective Tissue Types and Disorders

Connective tissues vary in vascularization and function. Disorders can arise from defects in ECM components.

• Poorly Vascularized Tissues: Tendons, ligaments, and cartilage have limited blood supply, affecting healing.

• Inherited Disorders:

  • Ehlers-Danlos Syndrome: Mutations in collagen genes cause weak connective tissue, hypermobile joints, and fragile skin.

  • Osteogenesis Imperfecta: Defective collagen leads to brittle bones prone to fracture.

• Sprains and Tears: Ligament injuries range from mild stretching to complete tears, affecting joint stability.

Example: Anterior cruciate ligament (ACL) tears are common sports injuries requiring surgical repair.

Carbohydrates in ECM

Carbohydrates are classified by size and function in the ECM.

• Monosaccharides: Simple sugars (e.g., glucose, fructose, galactose) with 3-7 carbon atoms.

• Disaccharides: Double sugars formed by dehydration synthesis (e.g., sucrose, lactose).

• Proteoglycans: Proteins with attached GAGs; major components of cartilage and other connective tissues.

Equation:

$\text{Monosaccharide}_1 + \text{Monosaccharide}_2 \xrightarrow{\text{dehydration}} \text{Disaccharide}$

Table: Major ECM Proteins and Functions

Protein	Location	Function
Collagen	Connective tissues, skin, bone	Tensile strength
Elastin	Skin, lungs, blood vessels	Elasticity
Proteoglycans	Cartilage, ECM	Hydration, resilience
Glycosaminoglycans	ECM	Matrix structure, signaling

Summary

Understanding protein synthesis, membrane trafficking, and ECM composition is essential for grasping cell and tissue function in anatomy and physiology. These processes underlie development, repair, and disease mechanisms in the human body.