C2.1: Chemical Signaling

Ligands

A molecule that binds specifically to a receptor site of another molecule (chemical signals)

Ligand-Binding Site

the specific location on the receptor protein where a signaling molecule binds

Target Cells

cells that have receptors for a particular hormone/ligand

Ligand/Enzyme Similarities (3)

-Substrate/ligand must bind at a specific site (ligand binding site for ligands, active site for enzymes)

-physical and chemical properties of ligand and binding site of receptors are complimentary (same w/ enzyme and active site)

-receptors remain unchanged by binding (besides induced fit), receptor/active site revert back to original shape once ligand/enzyme leaves

Ligand/Enzyme Differences (2)

-Substrate becomes product and releases, ligand stays the same

-substrate stays bound for short period of time, ligand stays bound for longer

Quorum

Set number of individuals needed for a group activity to begin

Quorum Sensing

Once set number of individuals met, certain activity or behavior occurs

-all cells of species secrete ligand in small amounts, as population of species increases, amount ligand increases

-once enough receptors are bound to ligands, gene expression changes

Vibrio fischeri

marine bacteria that resides in light organ of bobtail squid

-all bacteria cells produce autoinducer which binds to LuxR, receptor in cytoplasm of bacteria

-once bound, results in LuxR-autoinducer complex that binds to DNA and begins transcription of genes

-producer luciferase, catalytic enzyme that loses energy in the form of greenish-blue light

-light helps squid camouflage in moonlight

Requirement of Signaling Molecules

must have unique shape and chemical property to be distinguished by receptors, and be small/soluble enough for transportation

Diversity of Hormones

-can have amines (contains NH2) like epinephrine/melatonin

-can be peptides like insulin and glucagon

-can be steroids (nonpolar) like oestradiol, progesterone, testosterone

Diversity of Neurotransmitters

-amines (dopamine)

-gases (nitrous oxide)

-amino acids (glutamate, glycine)

-esters (acetylcholine)

Examples of Signaling Chemicals (4)

Hormones, Neurotransmitters, Cytokines, and Calcium Ions

Hormones

Produced by glands and transported via bloodstream

-blood transports hormones to all parts of body, only recognized by target cells that have proper receptors

-can start/inhibit certain processes and persist for hours

-ex. insulin, thyroxin, testosterone

Types of Glands

Endocrine and Exocrine

Endocrine Glands

Secrete internally w/out ducts, ex. pituitary gland, testes/ovaries

Exocrine Glands

Secrete out of organ w/ ducts, ex. pancreas/skin

Neurotransmitters

Produced by neurons and transported across synapses, binds to receptors in postsynaptic neuron, begins action potential (can be excitatory or inhibitory)

-persist for fraction of a second, quickly degraded or reabsorbed into presynaptic neuron

ex. acetylcholine, dopamine

Cytokines

Produced by almost all body cells, small proteins that control growth/activity of immune system and blood cells

Coordinates immune response by activating T-cells and macrophages, also regulates inflammation

ex. erythropoietin, interferon, interleukin

Inflammation

Body's initial response to injury, characterized by redness, swelling, and heat

Calcium Ions (Ca2+)

Used for signaling in neurons and muscle fibres, stored in sarcoplasmic reticulum of muscles

-binds to troponin, which blocks muscles contraction

-also arriving AP opens Ca2+ channels in neurons, allowing Ca2+ to diffuse into neuron and signaling vesicles w/ neurotransmitters to exocytose into synapse

Effective Distance of Signaling Molecules

Neurotransmitters/cytokines are local regulators

Hormones travel from secreting cells to target cells located all over body via bloodstream (far)

-ex. pituitary gland secretes luteinizing hormone (LH) to be recognized by testes/ovaries

Local Regulators

Signals that work only over short distances via diffusion

Types of Ligands

Ligands characterized by whether they can enter the cell or not

Hydrophilic or Hydrophobic

Hydrophilic Ligands

Cannot enter cell, transmembrane receptors in plasma membrane receive them w/ binding site facing outside

-receptors have band of hydrophobic AAs that stay embedded in phospholipid tails

Hydrophobic/Lipophilic Ligands

Enter cell, bind to intracellular receptors in cytoplasm or nucleus

-intracellular receptors have hydrophilic AAs so they can stay dissolved

lipophilic ligands transports w/ protein "cover" so they can travel in hydrophilic environments

Initiation of signal transduction by receptors

depends on type of ligand and receptor

If ligand cannot pass membrane (protein)

-transmembrane receptor structure changes temporarily, becomes catalytic and activates enzymes and/or produces secondary messengers which carry signals to effector

If ligand can pass through membrane (steroid)

Forms a ligand-receptors complex, binds to DNA and regulates gene expression, promotes/inhibits transcription

Neurotransmitter Receptors

Transmembrane, ligand binds and opens membrane channels, ions (Na+, Cl-) move into neuron via facilitated diffusion, changing membrane potential

-fires an action potential in nerves or contraction in muscle fibres

ex. acetylcholine

G-Protein Coupled Receptors

GPCR, transmembrane receptors that uses a second G protein

G-Protein

composed of three subunits (alpha, beta, gamma), GDP (guanosine diphosphate) bound to alpha, keeps g-protein inactive

GPCR Process

Ligand binds to receptors, changes G-protein structure

-GDP detaches, allowing GTP to bind which activated g-protein

-alpha subunit dissociates from receptors, moves to effector, initiates response

-beta and gamma move to another effector

Epinephrine Receptors

Epinephrine (fight/flight) binds to GPCR, activating G-protein

-activates enzyme adenylyl cyclase

-adenylyl cyclase converts ATP into cyclic AMP (cAMP), a secondary messenger

-amplifies signal until large-scale process begins (phosphorylation cascade)

ex. liver cells release glucose into bloodstream after epinephrine binds

Kinase

enzyme responsible for phosphorylation, adds phosphate from ATP to specific molecules like tyrosine

Tyrosine Kinase Receptors

Insulin binds and activates receptors by changing its structure, two tails of receptors join to form a dimer

-each tail phosphorylates the other

-vesicles w/ glucose protein channels fuse w/ plasma membrane, embedding channels, increasing rate at which glucose enters cell

Intracellular Receptors

Steroid hormones are hydrophobic and can pass through cell membrane, binds to receptors in cytoplasm

-hormone-receptors complex enters nucleus, attaches to DNA and activates protein production via increase gene expression

ex. oestradiol, progesterone, testosterone

Oestradiol

regulates release of reproductive hormones

-activates hypothalamus to release gonadotropin-releasing hormone (GnRH)

-triggers anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH)

-during ovulation, transcription of GnRH increases

Full Oestradiol Process (simple)

oestradiol diffuses through plasma membrane, forms receptor-hormone complex, enters nucleus, acts as transcription factor

Hypothalamus

A neural structure lying below the thalamus; it directs several maintenance activities (eating, drinking, body temperature), helps govern the endocrine system via the pituitary gland, and is linked to emotion and reward.

GnRH

gonadotropin-releasing hormone, causes pituitary to release LH and FSH

Progesterone

Produced by ovary, responds by transcribing insulin-like growth factors, promoting cellular proliferation (division) for maintaining endometrium (uterine lining)

Types of Feedback

Positive or Negative

Positive Feedback

end produce amplifies product formation

ex. calcium-induced calcium release

-IP3 (inositol triphosphate) release Ca2+ from ER, Ca2+ activates IP3 receptors, which further increase Ca2+ release

Negative Feedback

End product inhibits product formation

ex. testosterone:

-GnRH targets anterior pituitary gland, releases LH, releases testosterone from testes

-increased testosterone signals anterior pituitary to decrease LH, which then signals hypothalamus to decrease GnRH