Biomembranes and Membrane Proteins

• Biomembranes contain a lipid bilayer and embedded proteins, glycoproteins, and glycolipids.

Membrane Protein Association

• Proteins associate with membranes in three ways: as integral membrane proteins, lipid-anchored proteins, or peripheral proteins.
• Integral membrane proteins span the plasma membrane, with an extracellular, transmembrane, and cytosolic domain.
• Lipid-anchored proteins are covalently attached to lipids in one leaflet, anchored to the hydrophobic core.
• Peripheral proteins attach to hydrophilic phospholipid head groups, integral membrane proteins, or lipid-anchored proteins and often link the membrane to the cytoskeleton or extracellular matrix.

Phospholipid Transfer

• Phospholipids do not readily transfer between biomembrane leaflets.
• Flippases, membrane proteins, facilitate phospholipid movement between leaflets.
• There are three main types of flippases namely flippases, floppases, and scramblases.
• Flippases and floppases require ATP.

Glycoproteins and Glycolipids

• Glycoproteins are integral membrane proteins covalently bound to carbohydrates.
• Glycolipids are membrane lipids covalently bound to carbohydrates.
• Carbohydrate chains of glycoproteins and glycolipids extend into the extracellular space.
• Glycolipids and glycoproteins enable cell recognition.

Biomembrane Dynamics

• Biomembranes are dynamic, growing and retracting with changing cellular needs.
• Biomembrane growth requires the synthesis and incorporation of new phospholipids, sphingolipids, and cholesterol.

Synthesis Challenges

• The hydrophobic nature of biomembrane components presents a challenge for cells.
• Water-soluble precursors allows the synthesis of these macromolecules.
• Precursors are integrated into the biomembrane.
• Enzymes bound to the membrane convert precursors into their mature form.

Fatty Acid Synthesis

• Fatty acids are synthesized in the cytosol from two-carbon acetyl groups from acetyl-CoA.
• The initial acetyl-CoA binds to the enzyme fatty acid synthase.
• Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA, a three-carbon molecule.
• Malonyl-CoA is added to the initial acetyl-CoA bound to fatty acid synthase.
• The third carbon on malonyl-CoA releases, which forms an acetyl group.
• Chain growth continues with malonyl-CoA addition until a full fatty acid is produced.

Phosphoglyceride Synthesis

• Fatty acid converts to fatty acyl-CoA in the cytosol.
• Enzymes in the smooth ER catalyze the reaction between two fatty acyl-CoA molecules and glycerol 3-phosphate.
• Phosphatidic acid is generated and inserted into the cytosolic leaflet of the ER membrane.
• Head groups added to phosphatidic acid generates the phosphoglyceride.
• Desaturase enzymes act on phosphoglycerides, enabling fatty acids to acquire double bonds.

Sphingolipid Synthesis

• Sphingolipid synthesis occurs in the smooth endoplasmic reticulum.
• Palmatoyl-CoA, a 16-carbon fatty acyl CoA, enters the ER and binds to serine.
• A second fatty acyl CoA binds to palmatoyl-serine, forming ceramide.
• Ceramide is sent to the Golgi, where a head group is added, forming a sphingolipid.
• Sphingolipids are sent from the Golgi to final destinations in the cell.

Cholesterol Synthesis

• Cholesterol precursors are synthesized in the cytosol.
• These precursors are embedded in the cytosolic leaflet of the smooth ER membrane.
• Enzymes in the ER membrane convert these precursors into cholesterol.

Transport Mechanisms

• Phospholipids and cholesterol must be transported to their final destination after synthesis in the smooth ER.
• There are three main transport mechanisms: vesicle formation and fusion, transport via binding proteins, and transfer at biomembrane contact sites.
• Vesicles form from the smooth ER, fusing with the target biomembrane.
• Phospholipids or cholesterol transport through the cytosol via binding proteins.
• Proteins at biomembrane contact sites facilitate transfer.
• Further modifications can occur once the biomolecules are in their final destination.

Role of Membrane Transporters

• Membrane transporters act as doorways to the cell and regulate the movement of molecules across cellular membranes.

Simple Diffusion Factors

• The rate of simple diffusion is affected by: temperature, concentration gradient magnitude, biomembrane surface area, molecule hydrophobicity and size.

Protein-Mediated Transport

• Based on the movement direction of molecules, protein-mediated transport is categorized into facilitated transport, active transport, and co-transport.
• Facilitated transport involves molecules moving down their concentration gradients with integral membrane proteins, including uniporters and ion channels.
• Active transport involves molecules moving against their concentration gradient via ATP-powered pumps.
• Co-transport involves the movement of one molecule against its concentration gradient while another moves down its gradient, performed by symporters and antiporters.