CHEM 433 Week 1 Hormones and Signaling Pathways

hormones

intercellular signal released extracellularly that interact with cell surface molecules and are converted into intracellular signals that affect protein activity and or gene expression in the cell

endocrine hormone

hormones released into bloodstream to act distantly from originating tissue eg. insulin, epinephrine, testosterone

paracrine hormone

local mediator signals that interact only with cells in the immediate vicinity eg. interleukins-1, antiviral protein

autocrine hormone

hormones acting back on the cells that released them eg. insulin, leptin, IGF-1

juxtacrine hormone

contact dependent signaling eg. Notch pathway

pancreas

mostly releases digestive enzymes eg. rnase, amylase, trypsin

What is glucagon?

A pancreatic islet peptide hormone.

What does glucagon inhibit?

Glycogen synthesis.

What processes does glucagon stimulate?

Glycogenolysis and lipolysis.

How does glucagon stimulate glycogenolysis and lipolysis?

By stimulating cAMP and Ca2+.

insulin

pancreatic islet peptide hormone that stimulates glycogen synthesis in muscle, liver, adipose

somatostatin

pancreatic islet peptide hormone that inhibits release of insulin and glucagon

What are the purpose of thyroid hormones?

influence energy status/metabolism as a whole with T3 and T4

Hypothyroidism

lethargy, obesity, in low iodine areas, goiter

What does hypothyroidism during development cause?

cretinism

hyperthyroidism

racing heart, elevated blood pressure, weight loss, bug-eyed, insomnia

how are thyroid hormones synthesized?

Y residues are iodinated in thyroglobulin and creates stable radicals that cross link to form aldehyde. the inactive thyroglobulin is cleaved to yield soluble T3 and T4

How are T3 and T4 carried through the body?

Carried by proteins in blood, passes into cells, and binds to Thy-R to activate a transcription factor increasing the expression of metabolic enzyme genes

What would an excess of thyroid hormone cause?

a faster metabolism, short stature, mental retardation

agonist adrenergic receptors

elicit hormonal response

antagonist adrenergic receptor

prevent hormonal response

B adrenergic receptors

activate adenylate cyclase

a adrenergic receptors

inhibit adenylate cyclase

steroid based hormone glucocorticoids

govern nutrient metabolism, inflammatory responses, and stress

steroid based hormone mineralocorticoids

govern kidney function and ionic/water balance

steroid based hormone gonadol steroids

govern sex hormones testosterone, progesterone, and estradiol

How do steroid hormones transport?

pass through cystolic membrane and interact with a cytoplasmic receptor to travel to nucleus and act as a transcription factor

What are causes of Addison's Disease?

Cancer, loss/damage to adrenal glands, HIV

What are symptoms of Addison's disease?

Hyperpigmentation, hypoglycemia, muscle weakness, fatigue, weight loss, ionic imbalance

What are treatments of Addison's disease?

glucocorticoids, cortisol

What causes Cushing's disease?

pituitary tumor signalling too much adrenal cortisol production, adrenal cancers, overuse of steroids

What are symptoms of Cushing's disease?

fatigue, hyperglycemia, moon face, loss of skin integrity

What are treatments for Cushing's disease?

tumor surgery, discontinue steroid use, drugs to control cortisol production

What do opioid peptides do?

Endorphins that regulate pain sensation and extreme emotion

What effects does the hormone NO have?

vasodilation, cytotoxicity of macrophages

examples of primary signal messengers

hormones, light, nutrients

examples of transducing signal molecules

cell membrane proteins, G-proteins, adenylate cyclase

examples of second messenger signals

calcium, cAMP

examples of signaling downstream effects

protein kinases activate/inactivate enzymes or proteins and make changes in transcription

regulatory integration

process by which a cell collects, interprets, and integrates multiple extracellular and intracellular signals, allowing it to coordinate appropriate physiological responses

What are the six basic types of signal transduction?

GPCRs, RTKs, RGC, adhesion receptors, gated ion channels, and nuclear receptors

GPCRs

signaled by epinephrine and received by b adrenergic receptor

adenylate cyclase

Activated by a G-protein. Converts ATP to cyclic AMP in response to an extracellular signal.

forskolin

activates most adenylate cyclase and works to lower blood pressure

How is protein kinase A (PKA) activated?

adenylate cyclase activates 4 cAMP molecules that bind to dissociated PKA regulators and PKA becomes active monomer that phosphorylates Ser/Thr residues

How does the cholera toxin affect cell signaling?

blocks GTP hydrolysis so adenylate cyclase produces 100x more cAMP and causes a constant intestinal Na pump causing massive loss of NaCl and water across intestinal epithelial fluid.

Explain the medical significance of b blockers.

drugs like propranolol and metoprolol are used to combat heart disease, cardiac arrhythmias, and hypertension because they are competitive antagonists of b receptors which block epinephrine effects.

How do the b blockers, propranolol and metoprolol, work?

Slowing and strengthening contraction of the heart and thus lowering the oxygen demand of the heart

how are receptor tyrosine kinases activated?

via ligand binding inducing dimerization

what do RTKs activate?

they phosphorylate tyrosine residues on itself and other proteins, inducing intracellular signaling that often promotes growth

Ras

a subfamily of GTPases that regulates cell growth via Ser/Thr protein kinases

Rho

a subfamily of GTPases that reorganizes cytoskeleton with Ser/Thr protein kinases

Arf

a subfamily of GTPases that activates cholera toxin A subunit, regulates vesicular pathways, and activates phospholipase D

Rab

a subfamily of GTPases that plays a role in secretory and endocytotic pathways

Ran

a subfamily of GTPases that functions in transport of RNA and proteins in and out of the nucleus

common mutation of Ras

causing uncontrolled cell growth, also known as cancer, due to the loss of GTP hydrolysis, trapping Ras on

what pathway does NO signaling operate through?

guanylyl cyclase

nitroglycerin

breaks down to produce NO, used to treat cardiac issues through strong vasodilation

drugs that target resetting cyclic nucleotide signal

Phosphodiesterase (PDE)

How does Sildenafil (Viagra) work?

inhibits PDE which hydrolyzes more cGMP and relaxes smooth muscle that increases blood flow

nonpolar signaling molecules and hormones can pass through plasma membrane

true

describe the process of cellular signaling through nuclear receptors

nonpolar molecules or hormones pass through membrane to hormone receptors in cytoplasm or nucleus and the complex binds to hormone response elements to affect gene expression