Plasma Membrane and Phospholipids

• The plasma membrane contains phospholipids that assemble into a double-layered arrangement known as the lipid bilayer.
• The lipid bilayer is semi-permeable, allowing some molecules to pass through while restricting others.
• Specialized proteins within the plasma membrane aid in transporting molecules in and out of the cell.
• Hydrophobic molecules and small neutral molecules are able to diffuse through the plasma membrane with ease.

Phospholipids

• Phospholipids are individual molecules that do not form polymers but group together.
• The phospholipid head group attaches to the phosphate group, determining its location within the cell membrane based on its chemical properties.
• The phosphate group is hydrophilic and charged.
• Glycerol, a 3-carbon chain with three hydroxyl groups, forms the backbone of the phospholipid.
• Two long hydrocarbon chains form the fatty acid tails, whose composition and bond number affect membrane rigidity.

Six Major Types of Phospholipid Head Groups

• Polar examples include PI, PG, and CL.
• Charged examples include PS, PE, and PC.

Other Common Lipids in the Plasma Membrane

• Cholesterol is a significant component of animal tissues' plasma membranes and has a hydroxyl group to interact with the membrane surface.
• Glycolipids have a sugar carbohydrate group attached but lack a phosphate group, often participating in cell signaling.
• Commonly, Glycolipids have sphingosine and glycerol backbones
• Sphingomyelin is similar to a phospholipid but contains a sphingosine backbone instead of glycerol.
• Sphingomyelin is common in myelin sheaths that wrap around nerve cell axons.

The Formation of the Plasma Membrane

• Micelles are droplets that form when phospholipids are surrounded by polar water, with fatty acid tails clustered in the center.
• Liposomes are tight bilayers with a hollow middle, formed by phospholipids in polar water.
• Phospholipids form a monolayer at the water-atmosphere boundary, with polar head groups facing the water.
• Phospholipids form bilayers within cells, with polar head groups oriented towards the aqueous environment inside and outside the cell and tails in the middle.

Plasma Membrane Leaflets

• The phospholipid bilayers in cells are called leaflets.
• The cytosolic face (or leaflet) of the bilayer faces the interior of the cell or cytoplasm.
• The exoplasmic face (or leaflet) faces the cell's exterior.
• For organelles with a single-layer plasma membrane, the endoplasmic face is called the luminal face.

Composition of the Plasma Membrane Leaflets

• The amounts of SM, PC, PS, and PI vary between the exoplasmic and cytosolic leaflets in the plasma membrane.
• Exoplasmic Leaflet:
  • The major components include positively charged phospholipids like PC and SM.
  • Glycolipids are found here.
• Cytosolic Leaflet:
  • Primarily made up of neutral and negatively charged phospholipids like PS.
  • PE, a positive and polar phospholipid, is also a major component.

Maintaining Lipid Asymmetry

• Cells use asymmetry to maintain the function of the plasma membrane and organelle membranes.
• Floppases:
  • Selective floppases maintain the presence of PC, sphingomyelin, and cholesterol in the exoplasmic leaflet.
• Flippases:
  • Selective flippases maintain the presence of PS, PE, and PI in the cytosolic leaflet.
• Scramblases:
  • Scramblases disrupt membrane asymmetry by randomizing phospholipids.

The Selective Permeability of the Plasma Membrane

• Molecules that can diffuse freely:
  • Small uncharged and hydrophobic molecules such as oxygen, nitric oxide, and carbon dioxide.
  • Requires a sufficient gradient moving them from high to low concentration areas.
• Water moves through aquaporins, passive transport channels with a hydrophilic interior.
• Molecules that cannot diffuse freely:
  • Hydrophilic compounds and large molecules.

Tonicity

• Tonicity measures osmotic pressure in a cell, reflecting relative solute concentrations on either side of the membrane.
• Hypertonicity:
  • Higher solute concentration outside the cell leads to water outflow and cell volume reduction.
• Isotonicity:
  • Equal solute concentrations inside and outside the cell, the ideal state for a cell.
• Hypotonicity:
  • Lower solute concentration outside the cell leads to water inflow.
  • It can cause cell swelling and lysis.

The Fluid-Mosaic Model

• Membranes are considered a two-dimensional liquid where lipid and protein molecules can diffuse.
• The "mosaic" part describes the multiple components of membranes, beyond just the phospholipid bilayer.
• The "fluid" part means lipids and other molecules can move freely within the membrane's two-dimensional plane.
• Membrane Constituents:
  • Phospholipids, cholesterol, and proteins can combine to form complexes.
• Hydrophilic Groups:
  • Phospholipid head groups can interact with hydrophilic parts of membrane proteins.
• Lipid Raft:
  • A cluster of membrane proteins, phospholipids, and other constituents.

Factors Affecting Membrane Fluidity

• Temperature:
  • Higher temperatures increase membrane flexibility.
• Lipid Content:
  • Shorter lipid chains are more mobile than longer chains.
  • Unsaturated lipids increase space in the membrane, leading to more movement.
• Cholesterol Content:
  • Cholesterol acts as a spacer at concentrations under 50%, increasing membrane fluidity.
• Protein Content:
  • Membranes rich in protein have less movement due to protein complexes and "rafts".

Membrane Proteins

• Signaling Molecules:
  • Proteins involved in cell communication.
• Integrins:
  • Facilitate cell adhesion and cytoskeleton movement.
• Receptors:
  • Facilitate endo- or exocytosis or are used in cell signaling.
• Channels and Transporters:
  • Move material across the membrane.
• Anchors and Junctions:
  • Help cells move and attach to other cells and the extracellular matrix.

Membrane Transport

• Membrane Transport:
  • Transports of cargo that cannot diffuse across the membrane.
• Passive Transport:
  • It moves molecules down the concentration gradient and requires no energy.
• Channel Proteins:
  • Form pores that allow water and small charged molecules to pass through.
  • E.g., Aquaporins.
• Carrier Proteins:
  • Undergo a conformational change to transport cargo.
  • They become active transporters when this change requires energy.
• Active Transport:
  • Moves molecules against their concentration gradient, using energy.
• Direct Active Transport:
  • Pumps use energy to move molecules.
  • E.g., Sodium/Potassium pump, uses ATP.
• Indirect Active Transport:
  • Uses the gradient established by a direct active transporter.
  • E.g., Sodium/Glucose symporter.
• Symporters:
  • Move molecules in the same direction.
• Antiporters:
  • Move one molecule in and another out.

Cellular Metabolism

• Catabolism:
  • Breakdown of cellular macromolecules to release stored energy.
  • Energy is stored as ATP.
  • End products are ATP, amino acids, and waste products.
• Anabolism:
  • Production of cellular macromolecules, consuming ATP.
  • End products are proteins, complex sugars, and fatty acids.

Adenosine Triphosphate (ATP)

• Primary energy source for cellular processes.
• Composed of an adenine molecule, ribose sugar, and three phosphates.
• Energy is stored between the second and third phosphates.
• Removing the third phosphate forms Adenosine Diphosphate (ADP) and releases energy to be used in cellular processes.

Guanosine Triphosphate (GTP)

• Similar to ATP, but with guanosine instead of adenosine.
• Provides energy for forming peptide bonds in protein translation.

Other High-Energy Molecules

• NAD+:
  • Converted to NADH by adding a hydrogen ion and two electrons.
• FAD:
  • Converted to FADH2 by adding two H+ ions and two electrons.

Mitochondrial Structure

• Cristae:
  • Folds of the inner mitochondrial membrane where enzymes convert high-energy compounds into ATP.
• Matrix:
  • The inside of the mitochondria where macromolecules are converted into small, high-energy compounds like NADH.

Cellular Respiration (ATP Production)

• Catabolic reactions that convert organic macromolecules into ATP.
• Removal of High-Energy Electrons:
  • High-energy electrons are stripped and stored in carriers like NAD+ and FADH.
• Creation of a Proton Gradient:
  • Electrons combine with protons and oxygen to create water.
  • Energy is stored as a proton gradient across the mitochondrial inner membrane.

Energy Storage

• Carbohydrates:
  • Stored mainly as glycogen in muscles and liver.
  • Muscle glycogen is readily available because liver glycogen needs to be broken down into glucose and secreted into the plasma.
• Fats:
  • Stored as triglycerides that must be broken down to release free fatty acids requiring energy to be transported into cells.
• Protein:
  • Stored mainly as skeletal muscle for when the body needs to use proteins as an energy source.

Sources of Glucose for Cellular Metabolism

• Monosaccharides:
  • Most commonly consumed in form of glucose.
• Disaccharides:
  • E.g., Lactose.
• Polysaccharides:
  • Act as energy storage molecules and must be broken down before use.

Getting Glucose into Cells

• Glucose enters the bloodstream from ingested foods, de novo synthesis, or glycogen breakdown.
• Glucose transporters (GLUT) found in most mammalian cells transport glucose into cells.

The 10 Steps of Glycolysis

• Distributing the catabolic reaction process over 10 steps releases the energy little by little.
• Distributing the process over 10 steps allows other monosaccharides to enter glycolysis and be converted.
• They do not result in the same energy yield as glucose

Glycolysis in Three Stages

• Stage 1:
  • Converts one glucose molecule into two glyceraldehyde 3-phosphate molecules (G3P) using the first five reactions.
  • Requires 2 ATP.
• Stage 2:
  • Each G3P enters the sixth and seventh reactions and is converted to a molecule called 3-phosphoglycerate.
  • Produces 1 ATP and 1 NADH per G3P, totaling 2 ATP and 2 NADH.
  • Net ATP is zero.
• Stage 3:
  • Converts 3-phosphoglycerate to pyruvate in three reactions.
  • Produces 1 pyruvate and 1 ATP per 3-phosphoglyceride, totaling 2 pyruvate and 2 ATP.
• By the end of the stage, one molecule has been converted to 2 pyruvate and has produced 2 ATP and 2 NADH
• Glycolysis Summary:
  • Glucose + 2 ADP + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH

The Fates of Pyruvate

• Pyruvate is further processed to continue the conversion of glucose to ADP and prevent it from discontinuing ATP
• Anaerobic Metabolism:
  • Occurs without oxygen.
  • Pyruvate undergoes fermentation to oxidize NADH to NAD+ so glycolysis can continue to create ATP.
  • Produces lactate (lactic acid) in animal cells and bacteria or ethanol in plant cells and yeast.
• Aerobic Respiration:
  • More ATP can be produced in the presence of oxygen.
  • Five Stages include: the conversion of pyruvate to acetyl-CoA, Krebs cycle, Electron transport chain, Chemiosmotic gradient, Formation of ATP by ATP synthase.

Converting Pyruvate to Acetyl-CoA

• After glycolysis, pyruvate is transported into the mitochondrial matrix.
• The pyruvate dehydrogenase complex removes a carboxyl group, converting pyruvate, NAD+, and CoA into acetyl-CoA, NADH, and CO2.
• Acetyl-CoA enters the Krebs cycle.

The Krebs Cycle

• Its function is to complete the oxidation of carbohydrates, proteins, and fats to produce substrates for cellular energy production.
• Acetyl-CoA enters by combining with oxaloacetate to form citrate.
• CoA is released and can be recycled.
• Citrate breaks down to remove two carbons and create succinate which can then release carbons in the form of tow CO2 and one GTP
• Products of the Krebs Cycle are 4 ATP, 10 NADH, and 2 FADH2

The Electron Transport Chain (ETC)

• It uses the energy of NADH and FADH2 to pump protons into the intermembrane space.
• NADH enters the ETC first and moves more protons.

Complexes of the ETC

• Complex 1:

  • Uses electrons from NADH to pump protons from the matrix to the intermembrane space.

• Complex 2:

  • Passes electrons from FADH2, releasing protons into the matrix.

• Complex 3:

  • Uses electrons from both NADH and FADH2 to pump protons.

• Complex 4:

  • Uses electrons from Complex 3 to pump protons.

ATP Synthase

• Concentrated protons within the intermembrane space generate ATP in a chemiosmotic reaction.
• It is located within the inner membrane and uses the proton gradient to phosphorylate ADP into ATP.
• One glucose molecule yields approximately 30 ATP through glycolysis and aerobic respiration.

Aerobic Respiration Summary

• Stage 1:
  • Pyruvate Oxidation converts pyruvate into acetyl-CoA in the mitochondrial matrix.
  • It produces one NADH and one CO2 per pyruvate.
• Stage 2:
  • The Krebs Cycle occurs, producing CO2, ATP, NADH, and FADH2
• Stage 3:
  • Electron Transport and Proton Pumping creates a chemiosmotic gradient of protons, also combining oxygen and protons to make water.
• Stage 4:
  • Chemiosmotic Gradient moves protons across the membrane into the matrix to generate ATP.
• Stage 5:
  • ATP is synthesized using the high concentration of protons in the intermembrane space to support the process of phosphorylating ATP
• Excess ATP:
  • Creatine kinases convert creatine and ATP into creatine phosphate and ADP.
• Deficiency in ATP:
  • Phosphate from creatine creatine phosphate is transferred to ADP to form ATP, so it does not require molecular oxygen and can occur during anaerobic conditions

Other Sources of Cellular Energy

• Fat Metabolism:
  • Free fatty acids (FFAs) are taken up into cells by fatty acid transport proteins.
  • Activation requires 2 ATP per each FFA.
  • Fatty acyl-CoAs are metabolized by beta-oxidation.

Transport of Fatty Acids

• Short fatty acid chains can diffuse into the mitochondrial matrix.
• Long chains must be transported by the carnitine shuttle.

Beta Oxidation

• Fatty acids are metabolized to release acetyl-CoA.
• Each 10 carbon fatty acid produces 5 acetyl-CoA total and produces 64 ATP total.

Destination of Protein Metabolites

• Amino acids are converted into ATP and enter cells’ metabolism.
• Some result in three-carbon molecules that synthesize glucose or enter glycolysis.
• Some form acetyl-CoA, entering the Krebs Cycle directly.
• Some enter as intermediaries of the Krebs Cycle.

Brain Energy Preferences

• The brain derives energy from ketones when glucose is not available.
• It cannot metabolize fatty acids directly.

Heart Energy Preferences

• The primary choice is fatty acids with some ketones.
• Operates exclusively on aerobic respiration and has the highest mitochondrial density, so anything which dramatically decreases blood supply to the heart can cause rapid, serious, and irreversible damage.

Skeletal Muscle Energy Preferences

• Major ATP production sources include glucose, fatty acids, and ketones.
• Has large glycogen stores which can be rapidly broken down
• Pyruvate undergoes anaerobic metabolism during heavy exercise.
• Fatty acids are the major ATP source in resting muscle.

Energy Demands (Skeletal Muscle and Exercise)

• Low Intensity:
  • When there is enough oxygen, stored fats are the primary energy source.
• Medium Intensity:
  • Shifts to using stored carbohydrates or glycogen, converted to glucose.
  • This newly converted glucose either undergoes aerobic or anaerobic respiration depending on oxygen levels
• High Intensity:
  • Muscle cells mainly depend on muscle glycogen.
  • Usually accompanied by low oxygen and anaerobic respiration with lactate accumulation.
  • Creatine phosphate is also used as ATP is depleted.
• Proteins are not used for energy production unless all other options have been exhausted.