Signaling Pathways and Metabolism

Signaling Pathways and Fed/Hunger States

• The presentation covers signaling pathways, receptor types, metabolic changes in fed and hunger states, and the roles of insulin and glucagon in metabolism.
• Learning objectives include explaining cell-to-cell communication, defining and describing receptors, explaining the importance of ketone bodies and metabolic changes in fed and hunger states, and outlining the roles of insulin and glucagon in metabolism, with examples of metabolic regulations for energy needs.

Cell Communication

• Cells communicate with each other and themselves.
• An analogy is used to illustrate how humans communicate (sound/ear)
• A diagram illustrates how brain cells communicate (neurotransmitter/receptor).

Modes of Signaling

• Direct signaling: proteins and other molecules contacting one another
• Juxtacrine signaling: signaling through cell-to-cell recognition
• Paracrine signaling: signaling through specialized molecules near target cell
• Autocrine signaling: signaling through cell interacting with same cell
• Endocrine signaling: signaling from a distant cell using hormones

Receptors

• Receptor types are classified by how the receptor works.
• Solubility dictates the signaling process
• Hydrophilic molecules can't penetrate the membrane (cell-surface receptors)
• Hydrophobic molecules can penetrate the membrane (intracellular receptors)

Binding - Response

• Receptor has two versions: ligand-receptor complex/affinity
• Ligand binds to a membrane receptor
• Receptor binding triggers an intracellular response.

Receptor-Ligand Relation

• Affinity: receptor-ligand interaction
• Agonist: creates a response
• Partial agonists: creates a response, but less than expected
• Antagonist: inhibits the receptor, blocks response

Receptor Types

• Metabotropic receptors: derived from metabolism
• Ionotropic receptors: derived from ions

Metabotropic Glutamate Receptor, mGluR

• Glutamate binds to the receptor in the cell membrane
• This activates intracellular signaling pathways
• Calcium is released

Ionotropic Glutamate Receptor, NMDA

• Glutamate binds, activating the channel and allowing ions to pass through the cell membrane.
• Ions pass through the receptor
• Ionotropic and metabotropic receptors occur in the process

G Protein Coupled Receptor - GPCR

• First messengers enter the cell
• Ligand binds to receptors
• The G protein interacts with the receptor
• Cyclic AMP is created
• Second messengers activate other enzymes
• The G protein activates many functions
• G proteins are activated when the ligand binds to the receptor

Fed/Hunger Regulation

• Body uses signaling pathways to maintain balance
• The body adjusts to maintain a constant level of nutrients
• The body regulates the pathways to maintain a constant energy level
• Pathways regulate the body's response to nutritional availability

Remember?

• Detailed metabolic pathways are shown for glycolysis and pentose phosphate pathways

An alternative energy way - Ketone Bodies

• Ketone bodies are created when the body needs energy
• Triacylglycerides are broken down to fatty acids, which then enter beta-oxidation
• Acetyl CoA enters the TCA cycle
• Ketone bodies are used in a catabolic pathway to create energy

Acetyl-CoA and Ketone Bodies

• Ketone bodies are created when the body cannot produce enough glucose
• The liver creates acetyl-CoA from amino acids and fatty acids
• Ketone bodies are used as an energy source by muscles and other tissues

Ketone Bodies

• The brain primarily uses glucose for energy
• Unlike other tissues, the brain cannot use fatty acids for energy
• When glucose is low, the brain can use ketone bodies for energy
• Ketone bodies are produced in the liver
• Ketone bodies are used by the brain and heart during starvation and diabetes

After Feeding

• Glucose, amino acids, and fats enter the body's system
• Insulin stimulates glucose transport into cells
• Excess glucose is stored as glycogen in the liver
• Excess lipids are stored as TAG (triacylglycerols) in adipose tissue

During Fasting/Starvation

• Glucagon is secreted to mobilize energy stores
• Glycogenolysis (breakdown of glycogen) releases glucose
• Gluconeogenesis produces glucose from non-carbohydrate sources
• Ketone bodies are synthesized in the liver from fatty acids

Insulin and Glucagon

• Insulin promotes glucose storage in cells and encourages glycogen synthesis.
• Glucagon promotes glycogen breakdown (glycogenolysis), releasing glucose from storage.
• Insulin regulates blood glucose levels—high levels stimulate insulin production, low levels stimulate glucagon production
• Glycolysis and gluconeogenesis rates are regulated by insulin and glucagon
• Glucose transporter types (e.g., Glut 4) are regulated by insulin
• Additional steps in the pathways and regulation occur

Insulin and Glucagon

• Insulin: Promotes glucose uptake, glycogen synthesis, and protein synthesis
• Glucagon: Promotes glycogen breakdown, gluconeogenesis, and lipolysis

Insulin and Glucagon

• Different pathways are regulated by different molecules.
• Mechanisms are in place to allow the body to shift between glucose (feeding) and ketone bodies (fasting) for energy.

Another Regulation Step

• Detailed pathway regulation of glycolysis and gluconeogenesis showing regulation points and steps.
• Shows how pathways are interwoven.

Stop Pyruvate

• Detailed diagram showing how the excess acetyl-CoA from Pyruvate can stop the enzyme PDH, and the control mechanisms of the citric acid cycle