Human biochem lecture 8

Lecture 8 – Lipids and Membranes

Date

• February 6th, 2025

Reading Material

• Biochemistry: Concepts and Connections, Chapter 10, Pages 305 – 321

Lecture Overview

• Disease of the Day: Tay Sachs Disease

  • A lipid storage disorder causing neurodegeneration.

• Chapter Overview:

  • Definition and types of lipids in biological systems.

  • Structure and function of membranes and membrane proteins, including protein placement.

  • The role of membrane proteins.

Tay-Sachs Disease – General Overview

Basics

• Predominantly genetic in origin.

• Autosomal recessive and non-sex linked due to mutation(s) in the HEXA gene.

• Impairs the function of hexosaminidase A, crucial for breaking down GM2 gangliosides in lysosomes.

• Ganglioside: A type of glycosphingolipid.

• Disease can manifest in three stages:

  • Infantile (most common)

  • Juvenile-onset (rare)

  • Adult-onset (very rare)

Tay-Sachs Disease Etiology and Pathology

• Prevalence: Rare, occurs in about 1 in tens of thousands.

  • More common in specific populations (e.g. Ashkenazi Jews) with carrier levels of 1:30.

• Symptoms:

  • Varies by type; infantile form:

    • Loss of motor function (3-6 months)

    • Neurodegeneration - seizures, blindness.

    • Typically fatal by age 4.

  • In adults and juveniles, progression is slower but still severe; adults may experience bipolar psychosis.

Pathology

Mechanism of Effects

• HEXA gene: Codes for hexosaminidase protein required to break down GM2 gangliosides.

• Gangliosides are membrane lipids found in neuronal tissues, which leads to deficits in motor function.

• Infantile form: Protein is entirely nonfunctional, while in juvenile/adult forms, functionality is reduced, causing GM2 ganglioside accumulation.

Tay-Sachs Disease - Diagnosis

Diagnostic Elements for Infantile Variant

• Regression of developmental milestones by 3-6 months.

• Symptoms include decreased attentiveness, sensitivity to sound, muscle twitching, and hypotonia.

• By 8-12 months, signs include diminished voluntary movement, blindness, and onset of seizures.

Macular Cherry-Red Spot

• A diagnostic sign often seen in the retina, presenting as a bright red spot due to lipid accumulation.

• Lipids build-up in the retina, leading to opacification elsewhere, retaining normal appearance near the macula.

Tay-Sachs Disease – Prognosis and Treatment

Prognosis

• Generally poor; early diagnosis correlates with worse outcomes.

• No effective treatments available for infants.

Management

• Supportive and palliative care to improve quality of life.

• Some adult patients may benefit from neuropsychiatric medications.

• Genetic counseling advised for at-risk individuals.

Lipids – Classification

Overview and Characteristics

• Broad classification of non-soluble (hydrophobic) biochemical molecules.

• Biological lipids typically possess both hydrophobic tails and hydrophilic heads.

• Tails are usually longer than heads, congregating due to hydrophobic interactions and van der Waals forces.

Fatty Acids

Structure

• Simplest lipid type with a hydrocarbon tail and a carboxylate head (R-COOH).

• Weak acids (pKa = 4.5); ionize to COO- groups, giving them hydrophilic properties at the head and hydrophobic properties along the tail.

Common Fatty Acids

• Examples include Stearic acid (saturated) and Oleic acid (unsaturated).

• Stearate ion: Depicted as a saturated fatty acid.

• Oleate ion: An unsaturated fatty acid with a cis double bond.

Classification of Fatty Acids

Saturated vs. Unsaturated

• Saturated: All carbon bonds are single (maximum hydrogen).

• Unsaturated: Contains at least one double bond, can be either cis or trans.

Naming Conventions

• Saturated: Count carbon tails straightforwardly.

• Unsaturated: More complex naming based on the position and type of double bonds.

Biologically Important Fatty Acids Table Overview

Triacylglycerols (Triglycerides)

Structure & Function

• Composed of three fatty acids linked to glycerol.

• Physical state at room temperature depends on double bond quantity (unsaturated = liquid).

• Functions:

  1. Energy storage/production.

  2. Insulation.

  3. Heat production.

Other Lipids

Soaps and Waxes

• Soaps: Produced via saponification (mixing triglycerides with strong bases).

• Acts as surfactants, not disinfectants.

• Waxes: Created through esterification of triglyceride components to long-chain alcohols, resulting in highly hydrophobic structures.

Biological Membranes

Phospholipids

• Main structural component, further categorized into subgroups.

• Proteins: Integral (transmembrane) and peripheral membrane proteins involved in signal transduction.

Membrane Structure

• Consists of a phospholipid bilayer with hydrophilic heads facing the environment and hydrophobic tails inward.

• Other components include sphingolipids and cholesterol which modulate fluidity and permeability.

Transport Across Membranes

Introduction

• Movement across lipid membranes is crucial for various cellular processes.

• Simple Diffusion: Occurs without transporters, described by the equation J = -P (C2 – C1).

Types of Trans-Membrane Transport

1. Facilitated Diffusion: Involves mediators such as pores, carriers, or permeases.

2. Selectivity Factors: Charge and size of ions impact selectivity through protein pores.

3. Co-Transport: Utilizes ion gradients created by ATP pumps to facilitate the transport of other molecules.

Example of Co-Transport Mechanism

1. Transport occurs with sodium ions and glucose via sodium-glucose cotranporters.

2. This utilizes sodium’s concentration gradient to assist glucose uptake into cells, primarily in the small intestine.