IPHY 3470: Exam 2 Study Guide

what are the Four Main Receptor Types?

CELL SIGNALING  

Membrane Transporters  

• Gated channels or open channels  

o But can’t be open on both sides  

• Different kinds of carriers:

o Uniport = 1 molecule in 1 direction (in or out)

o Symport = 2 molecules in 1 direction  

o Antiport = 2 molecules in opposite directions (one coming  in, one going out)

Diffusion  

• Passive process  

• High to low concentration  

• New movement until concentration is equal  

• Rapid over short distances  

• Directly related to temp  

• Inversely related to molecular size  

• In open system or across a partition  

GLUT Family  

1. Glut 1: glucose & hexoses – most tissues of body (always cell  membrane)

2. Glut 2: glucose & hexoses – liver, kidney, intestine  

3. Glut 3: glucose & hexoses – neurons  

what is the difference between Adenylate Cyclase and Phospholipase C?

4. Glut 4: glucose only – skeletal muscle, adipose tissue (intracellular  vesicles)

5. Glut 5: fructose – intestinal epithelium  

Glucose Transport  

• THE rate limiting step in glucose utilization  

• Transporters = non insulin (Glut 1) & insulin mediated (Glut 4)  • Resting muscle enters Glut 1 transporters in plasma membrane  • Exercise stimulated glucose uptake through Glut 4’s; majority  stored in intracellular vesicles  

o Contraction has “insulin like” effect of glucose uptake into  muscle  

o Can increase Glut 4 with training  

Receptor Locations  

• In cytosol or nucleus = lipophilic

• On cell membrane = lipophobic  

Four Main Receptor Types  

1. Channel receptor ions  

2. Receptor Enzyme (activate enzyme) If you want to learn more check out What is Dense Material ?

3. GPCR (open channel receptor)

Peptide Hormone is made of what?

4. Integrin (cytoskeleton)

Receptor Enzyme  

• Signal molecule binds to surface receptor – TK on cytoplasmic  side – phosphorylated protein – cellular response  

• 2 types:

o Kinase  

o Guanylyl Cyclase (converts GTP to cGMP)

• Ligands bind receptor enzymes = insulin, growth factors,  cytokines  

GPCR Don't forget about the age old question of What is covariance in statistics?

• 2 types:  

o Adenylyl Cyclase  

o Phospholipase C  

• Adenylyl Cyclase

o Ligand – receptor – AE (AC) – 2nd messenger (cAMP) – PK  (PK-A) – response  

• Phospholipase C  

o Ligand – receptor – AE (PLC) – 2nd messenger (DAG – in cell  membrane) – PK (PK-C) – cell response  

o Ligand – receptor –AE (PLC) – 2nd messenger (IP3 – cytoplasm) – Ca2+ signal from E.R. – cell response  

Channel Receptor Ions

• How ions create electrical signals  

• Receptor channels open or close in response to signal molecule  binding  

• Some channels directly linked to G proteins  If you want to learn more check out Can hydrophobic molecules aggregate spontaneously?

• Change in membrane permeability to Na+, K+, Cl- = creates  electrical signal = cellular response  

Phosphorylation  

• Phosphorylate = activate  

• Kinases = phosphorylate  

o Protein kinase transfers phosphate group from ATP  • Phosphatases = dephosphorylate

Desensitization/Adaption  

• Receptor activation triggers feedback circuit that shits off  receptor or removes it from cell surface  

o Alpha and/or beta receptor response  

• Exogenous antagonist = molecule that binds to a receptor &  opposes the action of another  

• Endogenous antagonist = substance that prevents the binding of  an agonist/ligand  Don't forget about the age old question of What is the difference between polar and non-polar covalent bonds?

Terminating Signals  

1. Ligand degraded by enzymes in extracellular space

2. Ligands removed from extracellular space  

3. Ligand bound to receptor; can terminate action of endocytosis of  receptor-ligand complex  

ENDOCRINE SYSTEM 

Cell-to-Cell Communication  

• Secreted from glands/cells = hormones  

• Secreted from neurons = neurohormones  

• Secreted from cells of immune system = cytokines  

• Gap junctions; contact dependent; autocrine (release & act on  same cell) or paracrine (release & act on another cell) signals  Hormones  

• Transported in blood (w/ or w/o transporter)

• Distant target tissue receptors (paracrine)

• Function:

o Control of: rate of enzyme reactions, transport of  

ions/molecules across cell membrane, gene expression &  protein synthesis  

o Exert at low concentrations (channel receptor ions) o Bind to target cell receptors  

▪ 1 hormone may act on only one OR multiple tissues  • Activity termination  If you want to learn more check out What are Some key characteristics of human developmen?

o Enzymes in blood will degrade hormone (even when bound  to receptor)

o Hormone-receptor complex = endocytosis – lysosomes  o Intracellular enzymes metabolize hormones

• Classification  

o Peptide/protein hormone  

o Steroid hormone  

o Amine hormone  

Peptide Hormone  

• Made from amino acids  

• Half life short (minute)

o Continuous release for continuous response

• Hydrophilic (lipophobic)

• No carrier protein  

• Receptor: cell membrane  

• 1. Enzyme degradation  

• 2. Hormone receptor endocytosis  

Steroid Hormone

• Made from cholesterol

• Half life long (>90 min)

• Hydrophobic (lipophilic)

• Carrier protein (hydrophobic)

• Receptor: intracellular (nuclear)

• 1. Intracellular enzyme metabolism  

• 2. Hormone receptor degradation (cytoplasmic)  

Amine Hormone  

• Derived from two amino acids  

o Tyrosine: catecholamines (dopamine, epi, norepi) & thyroid  hormones  

o Tryptophan: melatonin  

• Stored until secreted  If you want to learn more check out What is the difference between direct and representative democracy?

• Has similar peptide characteristics  

Endocrine Reflex Pathway  

1. Stimulus  

2. Afferent signal  

3. Integration  

4. Efferent signal  

5. Physiological action  

6. Negative feedback – turn off  

Simple Endocrine Reflex  

• Stimulus --> glands/cells --> hormone --> response  o Turned off by the response

• Ex: plasma Ca2+

o Decrease plasma Ca2+ --> parathyroid gland --> parathyroid  hormone --> increase plasma Ca2+ concentration  

o Response then turns off the signal  

• Endocrine cell acts as both a sensor & an integrating cell

Insulin  

Glucagon

• Fed state  

• Peptide  

• Beta cells of pancreas

• Short ½ life  

• Increase glucose oxidation  • Increase glycogen synthesis  • Increase fat synthesis  

• Increase protein synthesis  • Receptor: TK – receptor  

enzyme  

• Target cell: muscle, liver,  adipose tissue  

• Muscle & adipose goal:  

increase glu transport into  

cell by increasing Glut 4 in  

plasma membrane  

• Liver goal: increase glu  

utilization

• Fasted state  

• Peptide  

• Alpha cells of pancreas

• Long ½ life  

• Increase gluconeogenesis  • Increase glucogenolysis  

(breakdown)

• Increase ketogenesis (brain) • Increase fat utilization  

• Increase protein utilization  (gluconeogenesis)

• Receptor: GPCR – 2nd 

messenger cAMP

• Target cell: liver

• Goal: increase blood glu  

• In liver w/low glu level [ ] =  glucagon comes in , binds to  GPCR, cAMP --> glycogen -->  glu can exist the cell

Diabetes – Type 1 (10%)

• Autoimmune disease; cells destroyed  

• Insulin dependent  

• Insulin deficiency due to beta cell destruction  

• Lots of food outside the cell but the inside thinks the cell is  starving  

Diabetes – Type 2 (90%)

• Insulin resistant  

o Obesity makes tissue insulin resistant  

• Can smell ketones on breath – smells like alcohol

• Clinical consequences:

o Damages optic disk (retinopathy); diabetic foot; diabetic  ulceration  

Feedback Loops  

• 3 integrating centers:

o Hypothalamus, anterior pituitary, target of pituitary  hormone  

• Instead of response acting as negative feedback, hormones are the  feedback signal  

Hypothalamic – Hypophyseal Portal System  

• Adrenal cortex = stimulated by anterior pituitary trophic  hormone  

o Medulla = epinephrine & norepinephrine (tyrosine)

• Epinephrine  

o Stimulates glycogenolysis & lipolysis  

o Increase blood glu & fatty acids (increase heart rate) o Acts at liver, muscle, fat cells

o GPCR --> cAMP --> AE = AC

o CRH --> ACTH --> adrenal cortex --> cortisol  

▪ CRH & ACTH = trophic hormones  

Cortisol  

• Steroid hormone (long ½ life)  

• Long loop negative feedback  

• HPA pathway: CRH --> ACTH --> cortisol = immune, liver, muscle,  adipose tissue  

• Hypercortisolism  

o Adrenal tumor = secretes cortisol  

o Pituitary tumor = secretes ACTH

o Latrogenic = occurs 2nd to cortisol treatment  

• Cushing’s disease  

o Pituitary tumor – secretes ACTH

o Obesity, moon face, osteoporosis, insulin resistant, immune  suppression  

• Hypocortisolism – Addison’s disease  

o Autoimmune destruction of adrenal cortex  

o First place to look to solve the problem = adrenal cortex o Weight loss & decreased appetite, low blood sugar  

(hypoglycemia)

Growth Hormone  

• Site of secretion = pituitary (anterior)

• (+): GHRH (trophic hormone)  (-): somatostatin  

• Can act on liver, tissue, bone once released  

• Peptide – relatively short ½ life  

• Receptor = membrane receptor w/TK – receptor enzyme  1. Regulates growth & development  

2. Stimulates protein synthesis  

3. Acts at many tissues  

• Deficiency = dwarfism  

• Over secretion (children) = giantism  

• Over secretion (adults) = acromegaly  

Thyroid Hormone  

• Made from tyrosine & iodine

• Comes through symport – 2 molecules, 1 direction  • Receptor = nuclear receptor  

• Long ½ life  

• Negative feedback on anterior pituitary & hypothalamus  1. Basal metabolic rate  

2. Heat production  

3. Required for correct amounts of GH & development  • Hyperthyroidism (too much T3)

o Always hot, excess TSH

o Increase resting metabolic rate, increase heart rate • Hypothyroidism (too little T3)

o Decrease resting metabolic rate, decrease heart rate  o Always cold  

o Decrease protein synthesis (hair loss, thin nails)  1. Failure of thyroid  

2. Deficient stimulation of thyroid  

3. Inadequate dietary iodine  

• Thyroid goiters = iodine deficiency/excessive TSH stimulation  o Can occur in both hypo/hyper