Cell Junctions and Glucose Metabolism

Cell Junctions

Desmosomes:
- Cell-to-cell extensions that enable stretching.
- Found in the stratum spinosum of the epidermis.
Gap Junctions:
- Function as valves in the heart.
- Allow the spread of action potential from one cell to the next.

Plasma Membrane

Lipid Bilayer:
- Forms the basic structure of the cell membrane.
Transport Proteins:
- Integral Proteins: Embedded within the cell membrane, providing structural integrity.
- Peripheral Proteins: Located on the periphery of the cell membrane, such as receptor proteins.
- Enzymes: Can be located inside or outside the cell to facilitate reactions.
- Receptors: Bind to messengers (e.g., hormones) to initiate cellular responses.
Cytoskeleton:
- Peripheral proteins that link to the phospholipid bilayer and hold it down to the cell itself.
ID Markers (Glycoproteins):
- Serve as membrane surface identifiers.
- Determine blood type (A, B, AB, or O) on blood cells.

Transport Mechanisms

Diffusion:
- Movement of molecules from an area of high concentration to an area of low concentration.
Facilitated Diffusion:
- Requires a helper protein to facilitate the movement of molecules across the membrane.
- Specific for a particular molecule.
- Passive process (no energy required; follows the concentration gradient).
- Saturable (rate of transport limited by the number of available carrier proteins).
- Analogy: Ferryboat - specific for vehicles, passive as you sit and enjoy the ride, and saturable as the boat fills with people
Osmosis:
- Movement of water from an area of its high concentration to an area of its low concentration.
- Hypertonic Cell:
  - High solute concentration inside the cell relative to the outside.
  - Water moves into the cell, causing it to swell or lyse.
- Hypotonic Cell:
  - Low solute concentration inside the cell relative to the outside.
  - Water moves out of the cell, causing it to shrink (crenation).
- Isotonic:
  - Equal solute concentrations inside and outside the cell.
  - Equilibrium is maintained.

Active Transport

Sodium-Potassium Pump:
- Moves three sodium ions ( $Na^+$ ) out of the cell and two potassium ions ( $K^+$ ) into the cell.
- Requires ATP for energy.
- Involves shape confirmations of integral proteins.
- Three sodium ions bind to the intracellular side of the protein, ATP is cleaved into ADP and a phosphate, changing the shape of the pump and pushing sodium ions out.
- Two potassium ions bind extracellularly, the phosphate group is released, and the pump reverts to its original shape, pushing potassium ions in.
Secondary Active Transport (Cotransport):
- Utilizes the electrochemical gradient established by primary active transport (e.g., sodium-potassium pump) to move other molecules against their concentration gradients.
- Symport: Molecules move in the same direction.
- Antiport: Molecules move in opposite directions.
Endocytosis:
- Phagocytosis: Cell eating.
- Pinocytosis: Cell drinking.
- Receptor-Mediated Endocytosis: Specific molecules bind to receptors on the cell surface, triggering internalization.

Organelles

Functions of organelles should be reviewed using flashcards.

Mitosis

Stages: Prophase, Metaphase, Anaphase, Telophase, and Cytokinesis.

Glucose Metabolism

Four Stages:
- Glycolysis.
- Oxidation of pyruvic acid to acetyl CoA.
- Krebs (citric acid) cycle.
- Oxidative phosphorylation.
Catabolic Reactions: Breaking down molecules (indicated in blue).
Anabolic Reactions: Building molecules (indicated in purple).
Alternate Metabolic Pathways:
- Fermentation: Occurs when oxygen is not present, leading to the production of lactic acid (e.g., in muscles during intense exercise).
- Lipogenesis: Synthesis of triglycerides from excess glucose.
- Lipolysis: Breakdown of triglycerides into glycerol and fatty acids.
- Beta Oxidation: Fatty acids are broken down into two-carbon units, forming acetyl CoA.

Buzzwords

Oxidation: Loss of electrons.
Reduction: Gain of electrons.
Glucose catabolism involves chasing electrons to produce ATP.
- Nicotinamide adenine dinucleotide (NAD+):
  - Used throughout the process.
  - When reduced (gains electrons), it becomes NADH (carries two high-energy electrons and two hydrogen protons).
  - A hydrogen proton diffuses away when NAD+ is reduced to NADH because of the plus charge.
- Flavin adenine dinucleotide (FAD):
  - Used only in the Krebs cycle.
  - When reduced, it becomes FADH2 (gains two high-energy electrons and two hydrogen protons).
  - Doesn't start with a plus, so the two hydrogen atoms remain.
Krebs cycle involves a series of oxidation-reduction (redox) reactions.
Overall Equation for Glucose Metabolism: $C6H{12}O6 + 6O2 + 38ADP + 38P \rightarrow 6CO2 + 6H2O + 38ATP$ .
- Six-carbon glucose is broken down, with the six carbons ending up in carbon dioxide and the 12 hydrogens in water.
- Excess glucose is stored as glycogen (glycogenesis) in the liver and skeletal muscles.
- If glycogen storage is full, excess glucose is converted to fat (lipogenesis).

Glycolysis

Location: Cytosol.
A 10-step reaction series breaking down glucose into two three-carbon units of pyruvic acid.
Two ATP are invested to phosphorylate glucose.
Glucose is isomerized to fructose.
Another inorganic phosphate is added to each side, creating fructose 1,6-diphosphate (a symmetrical six-carbon chain).
Fructose 1,6-diphosphate is split in half, yielding two three-carbon molecules of glyceraldehyde-3-phosphate.
- Four ATP are produced, resulting in a net gain of two ATP.
- Two reductions occur, yielding four hydrogen protons.
- Alternate Metabolic Pathways:
  - If oxygen is present (aerobic), pyruvic acid proceeds to the oxidation of acetyl CoA.
  - If oxygen is not present (anaerobic), lactic acid is produced.
Equation for Glycolysis:
- Glucose ( $C6H{12}O_6$ ) is converted to two pyruvic acid molecules, two ATP, and two NADH.

Oxidation of Pyruvic Acid to Acetyl CoA

Occurs on the surface of the mitochondria.
Coenzyme A reacts with pyruvic acid to split off carbon dioxide.
The acetyl group temporarily joins coenzyme A and delivers the two-carbon unit to the citric acid cycle.
Two pyruvic acid molecules, with a loss of two carbon dioxide molecules, result in two acetyl coenzyme A molecules and two reductions (four hydrogens).
- Essential as the acetyl CoA serves as the junction point to merge amino acids and fatty acids for metabolism.

Krebs (Citric Acid) Cycle

A series of oxidations and reductions.
Occurs in the matrix of the mitochondria.
The acetyl group (two carbons) from acetyl CoA joins the cycle.
Oxaloacetic acid (four carbons) combines with the acetyl group to form citric acid (six carbons).
Citric acid is oxidized to alpha-ketoglutarate (five carbons), releasing one carbon dioxide and reducing $NAD^+$ to NADH.
Alpha-ketoglutarate is converted to succinic acid/succinate (four carbons), releasing another carbon dioxide and reducing $NAD^+$ to NADH.
ATP is produced by substrate-level phosphorylation (GTP donates a phosphate group to ADP).
Succinic acid is converted to fumaric acid/fumarate (four carbons), reducing flavin adenine dinucleotide (FAD) to FADH2 (occurs at a lower energy level than NADH production).
Fumaric acid is converted to malic acid via hydrolysis (addition of water).
Malic acid is oxidized to oxaloacetic acid, reducing $NAD^+$ to NADH.
Oxaloacetic acid begins and ends the Krebs cycle (PICUA molecule).
The cycle turns twice per glucose molecule.

*Equation:
2 Acetyl CoA + 6 $H2O$ --> 4 $CO2$ + 6NADH + 2FADH2 + 2ATP. Additionally, this generates the reducing equivalents (NADH and FADH2) for further ATP production in the electron transport chain.

Oxidative Phosphorylation

The final stage of glucose metabolism.
Involves the electron transport chain and chemiosmosis.
NADH and FADH2 shuttle high-energy electrons (24 total hydrogen) to the electron transport chain.
Cytochromes (electron transport chain carriers) facilitate the transfer of electrons.
At the end of the electron transport chain, two hydrogen protons combine with half a molecule of oxygen to form water.
Hydrogen protons are pumped across the mitochondrial membrane, creating a proton gradient.
As hydrogen protons diffuse back across the membrane through a proton pump, ATP is produced via chemiosmosis.
- Chemiosmosis: The coupling of the hydrogen proton pump with the manufacture of ATP (occurs in the cristae of the mitochondria).
- Overall, 34 ATP are made by chemiosmosis.

*Equation: Begins with 24 hydrogen from NADH and FADH2
-> passes electrons along the electron transport chain->combines with oxygen to form 12 water molecules and generates 34 ATP by chemiosmosis.