BIOLOGICAL MEMBRANES – Biochemistry Slideshow – First Year Block First

BIOLOGICAL MEMBRANES

• STRUCTURE AND COMPOSITION OF MEMBRANES
• BIOSIGNALING
• TRANSPORTATION MECHANISM

CHEMICAL COMPOSITION

• Lipids
• Proteins
• Carbohydrates
  • Lipids comprise 40%
  • Protein comprise 60%
  • Carbohydrates 1-10%

Content of Lipid Protein and Carbohydrates

LIPIDS

• Lipids are the esters of fatty acids and alcohol
• Other components
  • Phosphoric acid
  • Nitrogenous base
  • Carbohydrates

CHARACTERISTICS

• Insoluble in water
• Soluble in organic solvents
• Utilized by living organisms
• Include fats, oils, waxes and related compounds
• Amphipathic in nature
  • Polar or ionic nature head, hydrophilic in nature
  • Non-polar hydrophobic tail

PHOSPHOLIPIDS

Each layer of plasma membrane lipid bilayer is formed primarily by phospholipids which are arranged with their hydrophilic head groups facing the aqueous medium and their fatty acyl forming a hydrophobic membrane core

TYPES OF PHOSPHOLIPIDS

• Glycerophospholipids
  • Glycerol lipids   
    • Phosphatidyl choline
    • Phosphatidyl ethanolamine
    • Phosphatidyl serine
    • Phopshatidyl inositol
• Sphingolipids
  • Present in nervous system
  • 3 types
    • Sphingomyelin
    • Cerebrosides
    • Gangliosides

PERCENTAGE OF VARIOUS LIPIDS

LIPIDS COMPOSITION OF MEMBRANES

• Asymmetric composition
• Higher content of phosphatidyl serine and phosphatidyl ethanolamine in the inner leaflet
• Phosphatidyl serine contains a net negative charge, important for binding of positively charged molecules within the cell
• Phosphatidyl inositol is found only in the inner membrane, functions in the transfer of information

FATTY ACIDS

• Major components of lipids
• Non-polar tails of lipids are composed of long chain fatty acids attached to polar heads composed of glycerol-3-phosphate
• Saturated fatty acids
  • 50% of fatty acids are saturated
  • 16 to 18 carbon atoms
• Unsaturated fatty acids
  • 50% are unsaturated
  • Oleic acid
  • Arachidonic acid
  • Linoleic acid
  • Linolenic acid
    • Degree of unsaturation determines the fluidity of membranes

CHOLESTEROL

• Important component of biological membranes
• Hydrophilic polar heads exposed to water
• Hydrophobic fused ring system and attached hydrocarbon groups are attached towards the inner hydrophobic region
  • Cholesterol helps to maintain fluidity of membranes

PROTEINS

• Different types of proteins are present in membranes
  • Integral membrane proteins or intrinsic proteins
    • Trans proteins
  • Peripheral proteins
    • Lipid-anchored proteins

Integral membrane proteins or intrinsic proteins

• Deeply embedded in the membrane
• Firmly associated with membrane
• Portions are in Vander Waals contact with the hydrophobic region to seal the membrane
• Removable by agents that interfere with hydrophobic interactions such as detergents, organic solvents or denaturants

TRANSPROTEINS

• Some of the integral proteins span the whole breadth of membranes
• Hydrophobic side chains of the amino acids are embedded in the hydrophobic central core
• Hydrophilic regions protrude into aqueous medium on both sides of membranes
• Act as receptors for binding of hormones and neurotransmitters

Peripheral proteins or extrinsic proteins

• Weakly bound to the surface of membrane by ionic interactions and hydrogen bonding with the hydrophilic domains of integral proteins and with the polar head groups of lipids
• Can be removed without disrupting the membrane by relatively mild treatment that interfere with the electrostatic interactions or break hydrogen bond
• Provide mechanical support to the membrane

LIPID-ANCHORED PROTEINS

• Some membrane proteins contain one or more covalently linked lipids of several types
• They provide a hydrophobic anchor which inserts into the hydrophobic core of the membrane and holds the protein at membrane surface

CARBOHYDRATES

• GLYCOCALYX
  • Some proteins and lipids on the external surface of the membrane contain short chains of carbohydrates that extend into the aqueous medium, this hydrophilic carbohydrate layer is called glycocalyx
• FUNCTIONS
  • Protects the cell against digestion
  • Restricts the uptake of hydrophobic compounds
• COMPOSITION
  • Consists of oligosaccharide chains of approximately 5 sugars
  • Usually composed of D-Galactose, d-mannose, L-Fucose, N-acetyul glucosamine, N-acetyl neuraminic acid

GLYCOCALYX

• ATTACHMENT
  • Attached to the proteins either by
    • N- glycosidic bonds to the amide nitrogen of an asparagine side chain (N-glycosidic linkage)
    • Or
    • Through a glycosidic bond to the oxygen of serine

                (O-glycoproteins)

Transport Across Membranes

• Transport may occur in following ways
  • Active transport
  • Passive transport
• Passive transport
  • Diffusion
  • Facilitated diffusion
• Active transport
  • Primary active transport
  • Secondary active transport
• Transport of macromolecyles
  • Endocytosis
  • Exocytosis

Diffusion

• This is a process in which the free passage of substances occur from a high to low concentration
• Small, uncharged molecules e.g., O₂, CO₂, H₂O and lipid soluble substances such as steroid hormones cross membranes by simple diffusion

Facilitated Diffusion

• Transport of substances along a concentration gradient by a carrier system without the expenditure of energy is known a facilitated diffusion
• The transport proteins facilitate the transport of molecules that would otherwise be unable to cross the membrane e.g., the glucose transporter proteins embedded in the membrane help to transport the glucose from outside to inside the cell

Facilitated Diffusion

• These proteins bind glucose molecules from the extracellular fluid on the outside of the membrane and release them inside of the cell
• Amino acids and ions such as chloride, bicarbonate, sodium, potassium and calcium are transferred across the membrane by specific transport proteins by facilitated diffusion

Facilitated Diffusion

• Hormones regulate facilitated diffusion by changing the number of transporters available, e.g., Insulin increase glucose transport in muscle and adipose tissue
• Growth hormone increases amino acid transport in cells by affecting transporters for amino acids

Factors Affecting Diffusion

• Concentration gradient
  • Solutes move from high to low concentration
• Electrical potential
  • Solutes move towards the solution that has opposite charge
• The permeability coefficient of the substance for the membrane

Factors Affecting Diffusion

• Hydrostatic pressure gradient
  • Increased pressure will increase the rate and force of the collision between the molecules and the membrane
• Temperature
  • Increase in temperature will increase the movement of particles and hence increase the diffusion process

Active Transport

• This process of transport of substances involves carrier proteins and requires energy, is known as active transport. This transport often occurs against concentration gradient
  • Primary active transport
  • Secondary active transport

Primary active transport

• In this case energy is required for transport of substances but no coupled transport occur. The concentration of Na+ and K+ in the intra and extracellular fluid are maintained by an active transport system, the Na+, K+ ATPase
• The Na+, K+ ATPase works by the utilization of ATP and is about 1/3 of the total basal energy requirement of the human body
• This type of active transport is known as primary active transport

Secondary active transport

• The secondary active transport occurs when a substance is transported against its electrochemical gradient coupled to the transport of another substance down an electrochemical gradient established and maintained by primary active transport
• Example is transport of glucose into cells of the proximal kidney tubules or the intestinal epithelium in conjunction with sodium ions. The cells create a gradient in Na+ and then use this gradient to drive the transport of glucose from the lumen into the cell

Transport of Macromolecules

The movement of macromolecules inside (nutrients) and outside the cell (waste materials) is carried by endocytosis and exocytosis respectively

Endocytosis

• The receptor proteins present in the membrane involved in the import of substances by forming a small spherical structure known as endosome and the process is called receptor mediated endocytosis
• Examples: the lipoproteins, which distribute cholesterol to cells and transferrin which carries iron, are examples of macromolecules that enter cells in this way

Exocytosis

• The process involved in the secretion or release of macromolecules from cells  through the plasma membrane is known as exocytosis. Most of the cellular secretion and waste products are exported out of the cell by the process of exocytosis
• Examples: Proteins, various enzymes and peptide hormones like insulin and glucagon are transported outside the cell by enclosing in small spherical vesicles originating from Golgi apparatus
• The membrane of these vesicles fuse with the plasma membrane of the cell and the contents are released outside

Classification of transporters

• Membrane transport proteins can be classified according to the nature of the transport process that they promote
• UNIPORT
• SYMPORT
• ANTIPORT

UNIPORT

• This is the simplest type of transporter
• It can transport a single molecule at a time
• The glucose transporters found on the plasma membranes of most cells are uniports

SYMPORT

• This is required by its mechanism to transport two different molecular species at the same time, neither species can be transported on its own
• Example is the Na+ and glucose co-transport in the uptake of glucose from the gut 

ANTIPORT

• This like the symport involves the transport of two molecular species at the same time but in opposite directions
• The exchange of chloride ions and bicarbonate ions in the red cells and exchange of ATP and ADP across inner mitochondrial membrane are the examples of antiport

BIOSIGNALING

• The process of cell to send chemical message and respond in response of these signals is called biosignaling
• Two Types Of Molecules Are Involved In Biosignaling Messengers And Receptors

Molecules involved in biosignaling

• Chemical messengers
  • Also called signaling molecules
  • Transmit messages between cells
• Receptors
  • Proteins containing a binding site specific for a single chemical messenger and another binding site involved in transmitting the message
  • The second binding site may interact with another protein or with DNA

BIOSIGNALING

• SIGNAL TRANSDUCTION
• TYPES OF RECEPTORS
  • Surface receptors
  • Internal receptors
• SURFACE RECEPTORS
  • Gated ion channels
    • Ligand gated ion channels
    • Voltage gated ion channels
  • Surpentine receptors
  • Tyrosine kinase receptors

• Many JAK-STAT pathways are expressed in white blood cells, and are therefore involved in regulation of the immune system.
• The receptor is activated by a signal from interferon, interleukin, growth factors, or other chemical messengers.
• This activates the kinase function of JAK, which autophosphorylates itself (phosphate groups act as “on” and “off” switches on proteins).
•  The STAT protein then binds to the phosphorylated receptor, where STAT is phosphorylated by JAK.
• The phosphorylated STAT protein binds to another phosphorylated STAT protein (dimerizes) and translocates into the cell nucleus.
• In the nucleus, it binds to DNA and promotes transcription of genes responsive to STAT.