EF

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

Common Name

Systematic Name

Abbreviation

Structure

Melting Point (°C)

Capric acid

Decanoic acid

10:0

CH3(CH2)2COOH

31.6

Stearic acid

Octadecanoic acid

18:0

CH3(CH2)16COOH

69.6

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.