Exam 2: Physiology Flashcards

Question

Restricted Diffusion

Answer 1

Channel proteins present in lipid bilayers that provide diffusional pathways. Rates of diffusion of molecules strongly influenced by molecular size.

Answer 2

1. **Diuretics** ⇒ furosemide * Inhibit Na/K/2Cl co-transporter in loop of Henle * Used to treat HTN 2. **L-DOPA** * Transported by neutral amino acid transports in CNS * Converted to dopamine * Treatment for Parkinson's disease 3. **Proton pump inhibitors (PPI)** ⇒ Omeprazole * Inhibits ATP-dependent proton pump in stomach * Treats acid reflux 4. **Antidepressants** * Target neurotransmitter re-uptake mechanisms in brain * Na-driven co-transport enzymes

Answer 3

**Solute carried through the membrane by a specific carrier protein via a series of conformational changes.** Rocking banana or alternating access model. **Rate of diffusion approaches a maximum rate:** 1. Time it takes carrier to undergo conformational change 2. Finite number of transporter molecules **Exhibits three important properties:** 1. Stereospecificity 2. Saturation 3. Competition

Answer 4

* Found in **RBC and vascular epithelium** * Including **BBB** * Transports: * **D-glucose** ⇒ K_m = 1.5 mM * **D-mannose** * **D-galactose** * Can discriminate between D-glucose and L-glucose * Deficiencies linked to seizures

Answer 5

**Insulin-regulated** glucose transporter found in **adipose and skeletal muscle**.

Answer 6

**Fructose** transporter found in the **small intestine**. Deficiencies linked to dietary fructose intolerance.

Answer 7

**Hydrophilic transmembrane pores.** Provides water-like environment for ion diffusion. **Does not require a conformational change** ⇒ extremely rapid ⇒ approaches diffusion rate in water

Answer 8

**ATP hydrolysis is directly coupled to solute transport.** _Transporters divided into 3 categories:_ 1. **P-type transporters** 2. **F and V type proton pumps** 3. **ABC transporters**

Answer 9

Representative of all transporters that use ATP **E1 and E2 conformations:** Selectively binds a different ion Promotes its translocation across the membrane

Answer 10

High degree of similarity between transporters. All have a **phosphorylated intermediate** in the **Post-Albers Cycle**. 1. Na⁺/K⁺-ATPase (Na⁺ pump) 2. Ca²⁺-ATPase (Ca²⁺ pump or SERCA) 3. H⁺/K⁺-ATPase (Proton pump)

Answer 11

**For every ATP→ADP ⇒ 3 Na⁺ out and 2 K⁺ in** * Found in virtually every cell * Accounts for ~33% of BMR * **Electrogenic** * More positive charges moved out than in * **Adds** **-5 mV to membrane potential** * **Maintains ionic hemostasis** * **Maintains osmotic balance** * Inhibited by cardiac glycosides * Digoxin and Digitoxin * Inotropic agents used to treat CHF

Answer 12

Important in maintaining osmotic balance: * Many **fixed anions confined to cytosol** * **Cations** required for **charge balance** brought in by pump * **Cations creates osmotic gradient** * **Pulls water into cell** * Inorganic ions counteract these forces * Na⁺ pump drives Na⁺ out of the cell * **Cl^- is kept out by the membrane potential**

Answer 13

For each ATP→ADP ⇒ 1 to 2 Ca²⁺ ions transported * Maintains low intracellular [Ca²⁺] * One located on plasma membrane * Removes Ca²⁺ from cytosol * One moves Ca²⁺ into organelles * ER * Sarcoplasmic reticulum of muscle cells * terminates muscle contraction

Answer 14

**Moves H⁺against electrochemical gradient using ATP.** * Location: * parietal cells of gastric glands in **stomach** * intercalated cells of late distal tubule and cortical collecting duct of **kidney** * Inhibited by Omeprazole

Answer 15

Follows Post-Albers Cycle mechanism. E1 and E2 No phosphorylated intermediate.

Answer 16

Found in **mitochondria and chloroplasts**. Run "backwards" **Synthesizes ATP in oxidative phosphorylation and photophosphorylation** Uses movement of H+ down its concentration gradient

Answer 17

Found in intracellular organelles such as lysosomes. **Pump proteins into organelles to acidify intraorganelle environment.**

Answer 18

* Large family of ATPases * All contain a highly conserved ATP binding cassette * Clinically important * Includes: * MDR transporter * CFTR * ABCA1 cholesterol transporter

Answer 19

* Class of ABC transporter * **Responsible for extrusion of cationic hydrophobic metabolites and drugs** * Expression ↑ by exposure to substrate

Answer 20

* Class of ABC transporter * **Responsible for Cl^- secretion by some epithelial cells** * pulmonary tree * pancreas * sweat glands * Deficiencies causes cystic fibrosis

Answer 21

* **Moves cholesterol and phospholipids to lipid-poor lipoproteins** * Major role in lipid homeostasis * Defects cause Tangier disease * see ↓ [HDL]

Answer 22

The movement of one solute is couple to the movement of another solute whose concentration gradient was establised via primary active transport. * Na⁺ almost always involved * Due to Na⁺ gradient set up by Na⁺/K⁺-ATPase * Cotransport or countertransport

Answer 23

**Solutes are transported in the same direction.** Important in absorbing epithelia of kidney and small intestine. Includes: 1. Na⁺/glucose cotransporter (SGLT1) 2. Na⁺/amino acid cotransporter 3. Na⁺/K⁺/2Cl^- cotransporter

Answer 24

* Located in **luminal membrane of small intestine** * Two binding sites on exterior side of transporter * One for Na⁺ * One for glucose * Stoichiometry of transport * 2 Na⁺/glucose ⇒ SGLT1 and SGLT3 * 1 Na⁺/glucose ⇒ SGLT2

Answer 25

* Found in a wide variety of cells * Thick ascending limb of the loop of Henle * Important in urine formation * Inhibited by Furosemide

Answer 26

Secondary transport where coupled solutes move in opposite directions. _Examples:_ 1. Na⁺/Ca²⁺ exchanger 2. Na⁺/H⁺ exchanger 3. Cl^-/HCO₃^- exchanger 4. Mitochondrial ADP/ATP exchanger

Answer 27

**Na⁺_Outside ↔︎ Ca²⁺_inside** * Helps maintain low intracellular [Ca²⁺] * Stoichiometry varies amoung cells types * **Usually 3 Na⁺ in ↔︎ 1 Ca²⁺out** * **Electrogenic** * Important in cardiac muscle

Answer 28

**Movement of 1 Na⁺ in coupled to movement of 1 H⁺ out.** * Found in virtually every cell type * Important role in: * regulation of intracelluar pH * cell volume * cell division

Answer 29

**Couples countertransport of Cl^-and HCO₃^-.** **AE1** important for transporting HCO₃^- into RBC in the lung and out of the RBC in the periphery.

Answer 30

ATP_{mitochondrial matrix} ↔︎ ADP_{intermembrane space} Allows oxidative phosphorylation to continue. Delivers ATP to cytoplasm for use by cells.

Answer 31

The new flow of water through a membrane. All membranes are at least somewhat water soluble. Concentration gradient expressed in terms of differences in solute concentration.

Answer 32

The amount of pressure needed to prevent the movement of water from an area of high concentration to low concentration. Driving force for osmosis.

Answer 33

The osmotic pressure of a solution in a cell is dependent on 2 factors: 1. Osmolarity of the solutes 2. Ease with which a solute traverses the membrane ⇒ reflection coefficient

Answer 34

**The concentration of osmotically-active particles.** **Colligative property** ⇒ dependent on the total # of particles in a given amount of solution but not the nature of the solute

Answer 35

**Describes the ease with which a solute can cross a membrane.** **σ = 0** ⇒ freely permeable ⇒ exhibits no osmotic pressure **σ = 1** ⇒ impermeable ⇒ provides osmotic pressure σ = 0.02 for urea σ = 1 for albumin and intracellular proteins

Answer 36

Defines the osmotic pressure of a solution:

Answer 37

*Biological property* of a solution **defined in terms of water movement across a membrane**. Dependent on the concentration of **impermeant solutes**. **For impermeant solutes, tonicity and osmolarity are the same.** **Tonicity (mOsm/L) = σgC**

Answer 38

Specific channels involved in water transport. * + 13 different aquaporins * different tissue distributions * different regluation * varying ability to transport small neutral molecules other than water * AQP1 ⇒ water only * APQ3 ⇒ water and glycerol * Tetramer of subunits each with hourglass-shaped pore

Answer 39

Distribution of AQP in the kidney tubule correlates with renal function. * Proximal tubule & descending thin limb of LoH * Have AQP present * Water moves freely * Iso-osmotic tubular fluid * Ascending thin limb & thick ascending limb of LoH * Do not have AQP * Water remains * Hypo-osmotic tubule fluid * Collecting ducts & distal tubules * Regulated by ADH * ⊕ ADH ⇒ ↑ [AQP2] ⇒ water moves out ⇒ concentrated urine * ⊖ ADH ⇒ ↓ [AQP2] ⇒ water stays in ⇒ dilute urine

Answer 40

**Voltage difference between the inside and outside of the cell** Outside of the cell is defined as V=0 **Counterbalances the diffusional driving force set up by the concentration gradient.**

Answer 41

1. concentration gradient 2. selective membrane permeability

Answer 42

**Net driving force** proportional to the _difference between membrane potential and ion's equilibrium potential_. **V_m - E_x** When net driving force ≠ 0 ⇒ net flux occurs. Direction given by sign of (V_m - E_x) V_m can typically be manipulated by applying external voltage across the membrane ⇒ creates driving force for ion.

Answer 43

Non-gated ion "channels" selective for particular ions Always in an open state Ex. Two pore K⁺ channel ⇒ K2P

Answer 44

3 Na⁺ out ↔︎ 2 K⁺ in Net movement of one ⊕ charge out Contributes ~ -5 mV to V_m

Answer 45

Passively distributes itself across the membrane in response to V_m **E_Cl = V_m** Relative ⊖ charge inside the cell inhibits Cl^- movement into cytosol

Answer 46

Membrane depolarized to threshold ⇒ action potential. 1. **Depolarization phase** * Na⁺ channels open rapidly * Membrane is Na⁺ selective * V_m ≈ E_Na * K⁺ channels have not opened yet 2. **Repolarizaton phase** * K⁺ channels open * Na⁺ channels inactivated * V_m approaches E_K 3. **Hyperpolarization phase** * K⁺ channels still open * Na⁺ channels closed and inactivated * V_m equals E_K 4. **Return to resting state** * Both K⁺ and Na⁺ channels have reset * Only K⁺ leak channels open * V_m approximately equal to E_K

Answer 47

Time during which an action potential cannot be elicited regardless of the stimulus. Due to fact that Na⁺ permeability has inactivated.

Answer 48

Time during which a larger-than-normal stimulus is required to elicit a propagated action potential. Due to fact that K⁺ permeability is still elevated.

Answer 49

**Between the absolute and relative fractory periods.** Time where one cannot elicit a propagated action potential regardless of the stimulus. Important in cardiovascular physiology where wave of AP spreads through the heart.

Answer 50

Hormones released into circulation by endocrine cells and travel to targe cells far from site of release.

Answer 51

Signalling molecule interacts with receptors on a neighboring cell. Ex. neurotransmission

Answer 52

Cells respond to a molecule they produced. Ex. T lymphocytes produce IL-2 to stimulate their own proliferation.

Answer 53

* Signaling molecule lipid-soluble and crosses the membrane * Binds to receptors inside the cell * Receptors bind to specific DNA sequences and control gene expression * Two categories: * Bind receptor in the cytoplasm * Bind receptor in the nucleus

Answer 54

* **Receptors bind their ligand in the cytoplasm** * Hormone-receptor complex translocates to the nucleus * Binds via **Zn-finger motifs** to **hormone response elements (HREs)** * Activate or inactivate transcription * Examples: * Glucocorticoid receptors * Mineralocorticoid receptors * Progesterone receptors * Androgen receptors

Answer 55

* Receptors always found in the nucleus * No translocation of the receptor into the nucleus is needed * Ligand must enter nucleus to bind * Ligand/receptor complex binds to HRE's * Alters transcription * Examples * Thyroid hormone receptor * Retinoic acid receptor * Vit D₃ receptor

Answer 56

**Transmembrane proteins** that undergo a **conformation change** upon ligand binding. **Elicits a change in transmembrane potential or generation of an intracellular second messenger.** Can be divided into several classes: * **Ligand-gated ion channels** * Nicotinic acetylcholine receptor * **Enzyme-linked receptors** * receptor tyrosine kinases * **Cytokine receptors** * **G-protein coupled receptors** * β-adrenergic receptor

Answer 57

* Liganding binds forms a selective pore in the membrane * Alters transmembrane potential * Excitatory receptors ⇒ depolarization * Inhibitory receptors ⇒ hyperpolarization * Very fast signaling

Answer 58

* **Receptors have intrinsic enzymatic activity** * Protein kinases * Phosphatases * Proteases * Nucleotide phosphodiesterases * **Ligands are** **polypeptide growth factors and hormones** * **Takes longer ⇒** minutes to hours * **Receptor tyrosine kinases (RTK)** are a major subclass * Insulin receptor * Epidermal growth factor receptor (EGFR) * Platelet-derived growth factor receptor (PDGFR)

Answer 59

* After activation, receptor itself is **autophosphorylated** on tyrosine residues on intracellular portion. * Phosphorylated tyrosine act as **recognition sites for intracellular signaling proteins.** * Those proteins are **phosphorylated by the kinase.** * Phosphorylation of substrates allows them to **act as downstream effectors.**

Answer 60

1. Insulin binds extracellular α-subunits of insulin receptor 2. Autophosphorylation of intracellular β-subunits 3. Facilitates binding of **insulin receptor substrates (IRS)** 4. IRS phosphorylated ⇒ serves as docking protein for downstream effectors 5. Two major pathways activated * **Phosphatidylinositol-3-kinase (PI3K)** * Converts PIP₂ ⇒ PIP₃ * Major changes in glucose and protein metabolism * **Ras pathway** * Increases gene expression

Answer 61

* **Cytokines ⇒ polypeptides that regulate growth and differentiation** * Interleukins * Interferons * Receptors do not have intrinsic enzyme activity * **Ligand binding ⇒ conformational change ⇒ activation of proteins kinases** * direct interaction with kinase * via adapter proteins that form kinase complexes

Answer 62

* **Receptors have 7 transmembrane alpha-helices** * Important role in many physiological processes * taste and vision * cardiac contractility * metabolism * BP control * **Transduction of signal via heterotrimeric GTP-binding proteins (G proteins)** * G proteins interact with **downstream effector proteins** * Phospholipases * Adenylyl cyclase * Ion channels * Systems then generate **secondary messengers**

Answer 63

**GTP-binding proteins with intrinsic GTPase activity.** * Heterotrimeric with α, β, and γ subunits * Variable α subunit * Classified based on α subunit which determines effects * Common βγ subunits * Have GDP bound to them at rest

Answer 64

1. Ligand binds 2. GPCR interacts with G-protein/ADP 3. GDP switched for GTP 4. G-protein dissociates into α/GTP complex and βγ complex 5. α/GTP complex and βγ complex interact with effectors proteins 6. ∆ secondary messenger levels 7. GTPase activity of α subunit acts as a timer for the transduction event * Once GTP hydrolyzed to GDP, heterotrimer complex reassembles and generation of 2nd messenger stops

Answer 65

Stimulates adenylyl cyclase. Examples: β-adrenergic receptors Glucagon receptors TSH receptors

Answer 66

Inhibits adenylyl cyclase. Examples: α₂ adrenergic receptors M₂ muscarinic receptors

Answer 67

G_s stimulates and G_I inhibits adenylyl cyclase. **Adenylyl cyclase ⇒ cAMP** cAMP binds regulatory subunits of protein kinase A (PKA) Dissociation of PKA complex ⇒ **activation of PKA** **PKA phosphorylates serine or threonine residues** **Alters activity of the substrate.** cAMP degraded by **phosphodiesterases**.

Answer 68

Epinephrine ↔︎ β-adrenergic receptors Glucagon ↔︎ glucagon receptors Both are G_S receptors. ⊕ adenylyl cyclase ⇒ ↑ [cAMP] ⇒ ⊕ PKA PKA activates glycogen phosphorylase and inhibits glycogen synthase. Results in increased glycogenolysis.

Answer 69

**Activates phospholipase C.** **Works via IP₃/DAG system.** Examples: α₁ adrenergic receptors M₁ muscarinic receptors Angiotensin II type 1 receptors

Answer 70

1. Ligand binds GPCR and resulting in G_Q activation 2. **G_Q stimulates phospholipase C** 3. PLC hydrolyzes **PIP₂ → IP₃ and DAG** 4. **IP₃ triggers release of calcium** from ER by opening IP₃ gated channels * ↑ [Ca²⁺] triggers downstream events * Mediated by **calmodulin** 5. **DAG activates protein kinase C (PKC)** by exposing ATP-binding site * Some isoforms of PKC further stimulated by Ca²⁺ * **PKC alters activity of downstream effectors** * transcription factors * ion channels * MAP kinase