Body Water Compartments & Ion Distribution

Body Water Compartmentalization

• Water constitutes approximately 60% of lean body mass in humans.
• Body Water is distributed across two primary compartments separated by a cell membrane.
• Intracellular Fluid (ICF) makes up about two thirds of total body water, providing a specialized environment for cells.
• Extracellular Fluid (ECF) is about one third of total body water and is divided into plasma and interstitial compartments.

Ionic Composition Comparison

• Na+ concentration is much higher in extracellular fluid (140 mmol/L) compared to intracellular fluid (10 mmol/L).
• K+ concentration is much higher inside cells (140 mmol/L) than outside (4 mmol/L).
• Ca2+ levels greatly differ with 2.5 mmol/L extracellularly and 0.1 µmol/L intracellularly.
• Mg2+ is found at 1.5 mmol/L extracellularly and 30 mmol/L intracellularly.
• Cl- is more concentrated outside cells (100 mmol/L) than inside (4 mmol/L).
• HCO3- levels are 27 mmol/L in extracellular fluid and 10 mmol/L in intracellular fluid.
• PO43- is found at 2 mmol/L extracellularly and 60 mmol/L intracellularly.
• Glucose is present at 5.5 mmol/L extracellularly, varying from 0-1 mmol/L within cells.
• Proteins are far more concentrated inside cells (16 g/dL) compared to outside (2 g/dL).

Membrane Structure and Properties

• Membranes consist of an asymmetric lipid bilayer and have distinct inner and outer surfaces.
• Membranes are dynamic, fluid structures containing a lipid bilayer and associated proteins.
• The plasma membrane exchanges materials with the extracellular environment through exocytosis and endocytosis.
• Gap junctions within membranes are specialized areas that enable adjacent cells to communicate by exchanging materials.
• Plasma membrane has selective permeability, controlled by specific transporters and ion channels.
• Membranes form specialized compartments (organelles) within the cell, such as mitochondria, ER, Golgi, lysosomes, and nucleus.
• Membranes localize enzymes, facilitating biochemical reactions.

Membrane Dynamics

• Membrane dynamics can be affected by changes in membrane components, impacting water balance and ion flux.
• Digoxin or digitalis inhibits Na+-K+ ATPase and impacts membrane dynamics.
• Deficiencies or alterations in membrane components from mutations can lead to diseases.
• Choline-containing phospholipids (phosphatidylcholine, sphingomyelin) are predominantly in the outer leaflet.
• Aminophospholipids (phosphatidylserine, phosphatidylethanolamine) are mainly located in the inner leaflet.
• Carbohydrates covalently attached to membrane proteins are located on the external surface.

Interactions and Arrangement

• Membranes are formed via hydrophobic interactions, without covalent bonds.
• Phospholipids can rotate or move between inner and outer membrane surfaces with the aid of flippase enzymes in "flip-flop" action.
• Membrane structures and surfaces are protein-studded.
• Membranes are amphipathic with both hydrophobic lipid tails, and hydrophilic compartments.
• Triacylglycerols and cholesterol-esters are hydrophobic and not present in membranes.
• Individual lipid and protein units form a fluid mosaic model.

Membrane Permeability

• The lipid bilayer is impermeable to water-soluble molecules due to the hydrophobic core.
• Gases like oxygen, CO₂, nitrogen diffuse readily through the hydrophobic regions.
• Permeability coefficients of small molecules correlate with their solubilities in nonpolar solvents.
• A molecule's ability to diffuse measures permeability coefficient through the membrane.
• Rapid molecule movement through a membrane indicates a high permeability coefficient.
• H₂O can easily pass through the membrane.
• Na+ (sodium) goes comparatively slowly.

Membrane Components

• Membranes include lipids, carbohydrates, and proteins.
• Phospholipids, Glycosphingolipids, and Sterols form the major lipid portion of mammalian membranes.
• Cholesterol (unesterified cholesterol) is the most common sterol with animal cell membranes.

Membrane Lipids

• Glycerophospholipids have a glycerol-phosphate backbone and phosphatidate derivative.

  • Phosphatidic acid and an alcohol are glycerophospholipids.
    • Phosphatidylcholine is abundant with cell membrane.
      • Represents a large proportion of the body's choline store.
      • Important in nervous transmission and for labile methyl groups.
      • Dipalmitoyl lecithin prevents adherence, due to surface tension, of the inner surfaces of the lungs.
        • Its absence causes Respiratory Distress Syndrome (RDS).
        • LCAT (lecithin cholesterol acyl transferase) activity of HDL is relevant.
    • Phosphatidylinositol is a precursor of second mesengers, which play a role in cell signalling and membrane trafficking.
      • The most common phosphoinositide is phosphatidylinositol 4,5-bisphosphate (PIP2).
        • It is cleaved into diacylglycerol and inositol trisphosphate, which act like internal messenger signals.
    • Cardiolipin forms from phosphate groups to one glycerol molecule.
      • It is found in mitochondria and aids apoptosis.
      • It can be an antigenic signal on cells.

• Sphingolipids have a sphingosine backbone and ceramide derivative.

• Glycolipids have attached carbohydrates or carbohydrate chains that are distributed throughout the brain.

• Most commen streol in membranes is cholesterol.

Definitions

• Phosphorilation of glycerol backbone at 3rd position is glycerol 3-phosphate.
• Glycerol 3-phosphate + 2 Fatty Acid forms 1,2-diacylglycerol 3-phosphate, or phosphatidic acid.
• Serine amino acid + Palmitic acid will form Sphingosine
• Sphingosine + 1 Fatty acid creates Ceramide.

Lipases

• Phospholipases A1 and A2 hydrolyze esters of intact glycerophospholipids at C-1 and C-2 of glycerol respectively.
• Phospholipasses remove second fatty acids as well.

Effects on Fluidity

• Fluidity is directly proportional to temperature.

  • As temperature increases the structure transitions becoming disordered.

• Fluidity is directly proportional to the degree of unsaturated fatty acids.

  • Unsaturated bonds in the cis configuration increases fluidity.

• Fluidity is inversely proportional to the fatty acid chain length.

  • Hydrophobicity increases as chain length increases.

Glycoconjugates

• Oligosaccharide chains attach to plasma membrane components forming a carbohydrate layer (glycocalyx).
• These information-rich surfaces play roles in cell recognition, adhesion, cell migration, blood clotting, immune response, and wound healing.
• Informational carbohydrate molecules are covalently joined to a protein or lipid which forms a biologically active molecule.
• Carbohydrate chains attach to the amino-terminal portion of the outside external surfaces.
• Presence of the carbohydrate on the surface of the membrane can be shown by the plant lectins.
  • Shown with the help of plant-based Lectins.
• Glycophorin is an integral membrane glycoprotein that influences flip-flop effectiveness.

Membrane Proteins

• Proteins in the plasma membrane function as enzymes, pumps, transporters, channels, structural components, antigens and receptors.
• Membrane proteins are arranged asymmetrically within the lipid bilayer that are loosely bound and can move through it.
• Integral proteins exist to perform multiple functions. They can:
  • interact extensively with phospholipids.
  • span a bundle of transmembrane segments that are alpha-helical.
  • are usually globular
  • are amphipatic.
  • They are made of hydrophilic ends.
• Peripheral proteins:
• cannot interact with hydrophobic areas.
• bind to hydrophilic regions.
• are integrated with other proteins.
• can be released from treatment with salt solutions.

Proteoglycans

Proteoglycans are bound together with hydrogen loose bonds, of different varieties including;

• Isoprenylations
• Cholesteralations
• Glycosylphosphatidolinositol
• Myristlaylation

Membrane Markers

• Membrane Markers are able to identify particular proteins with activities.
• This allows the location of these structures.
• Plasma membrane marker is 5'-Nucleotidase
• Endoplasmic Reticulum marker is Glucose-6-phosphatase
• Golgi Apparatus marker is GlcNAc transferase I
• Mitochondrial marker is ATP synthase

Membrane Function

• Membrane lipid content functions as an electrical insulator.
• Myelin
• Membrane protein content is found in protein content. Because; Electron Transport Chain that produces ATP needs enzymes. Transportation must be carried out with proteins throughout the structures.
• Achondroplasia is caused by Fibroblast Growth Factory changes.

Important Membrane Locations

• Rafts (Rafts): Specialized regions of the exoplasmic (outer) leaflet of the lipid bilayer exist enriched in proteins, and involved in signal transduction.*
• Cavealae: May be made of lipids, they are used in the protein signal transduction.
• Tight Junctions is made of surface structures.
• Gap junctions - allow structures to cross membranes
• Adherens junctions - specialized protein structures.

Transfer of Membrane information

• Membrane information is passed through small molecules, and Passive structures. Like Diffusion, passive membrane transfer is both large and small.
• Active membranes depend transport by; -Uniprot -Cotransport
• • Symport
• *Antiport

Types in Transport

Uniprot-System - Allows transport of one particular direction, bidirectionally. Con-transport - Transfer of one is reliant to stoichimitric transfer of materials at another location, example is that Glucose transporters rely on Sodium for transveral.