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Molecules to Organs > Exam 2: Physiology > Flashcards

Exam 2: Physiology Flashcards

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Organic Chemistry 101 flashcards
1
Q

Intracellular vs Extracellular

Ion Concentrations

A

Represent steady-state conditions.

Established and maintained by permeability properties of lipid bilayer and transport systems.

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2
Q

Membrane Structure

A

Held together by non-covalent interactions.

Membranes are:

Dynamic

Fluid

Asymmetrical

Amphiphathic

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3
Q

Membrane Components

A

Major components are lipids and proteins.

  • Lipids
    • Glycerophospholipids ⇒ most abundant
    • Sphingolipids
    • Cholesterol
  • Proteins
    • Integral
      • requires disruption with detergents to release
    • Peripheral
      • loosely attached
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4
Q

Glycerophospholipids

Structure

A
  • Glycerol backbone
  • Two long-chain fatty acids attached at C1 and C2
    • C1 ⇒ saturated FA ⇒ straight
    • C2 ⇒ unsaturated FA ⇒ kinked
  • Phosphate group attached at C3
    • Free acid
    • Ester with an alcohol
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5
Q

Glycerophospholipids

Headgroups

A

Net charge depends on the headgroup.

Affects the nature of the membrane surface.

Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) most abundant.

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6
Q

Uncharged

Membrane Lipids

A
  1. Phosphatidylcholine (PC)
  2. Phosphatidylethanolamine (PE)
  3. Sphingomyelin
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7
Q

Negatively Charged

Membrane Lipids

A
  1. Phosphatidylserine (PS)
  2. Phosphatidylglycerol (PG)
  3. Phosphatidylinositol (PI)
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8
Q

Sphingolipids

A

Derived from amino alcohol sphingosine.

  • Sphingomyelin ⇒ most common
    • polar choline head group
    • two acyl tails
  • Glycosphingolipids
    • one or more sugar residues attached
    • Gangliosides **
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9
Q

Gangliosides

A

Type of glycosphingolipid.

  • Oligosaccharide group with one or more N-acetylnuraminic acid residues
  • Carb portion protrudes out from membrane
    • Used in cell-cell recognition
    • Binds cholera toxin
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10
Q

Cholesterol

A

Steroid Alcohol

  • ↓ membrane fluidity
  • ↓ mobility of membrane components
    • ↓ deformibility
  • ↓ membrane permeability
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11
Q

Peripheral Membrane Proteins

A
  • Loosely attached by:
    • interaction with integral protein
    • electrostatic forces
    • hydrophobic domain
    • noncovalent binding to inositol head group of PI
    • lipid-achor linkage
  • Can usually be released without membrane disruption
    • alter pH
    • alter ionic strength
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12
Q

Lipid-Anchor

Linkages

A

Attaches peripheral membrane protein to membrane via a lipid covalently linked to the protein.

Several different linkages found:

  1. Glycosylphosphatidylinositol (GPI) anchor
    • PI attached to glycan ⇒ covalently linked to protein
    • Controls localization of a particular protein on the membrane
    • Detachment and reattachment of anchor ∆ protein activity
  2. Acyl-amide N-terminal linkage
  3. Thioester-linked acyl anchors
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13
Q

Membrane Fluidity

&

Affecting Factors

A

Individual lipids can diffuse laterally in the membrane.

Melting temperature (Tm)

Above ⇒ acyl side chains fluid and disordered ⇒ allows motion

Below ⇒ chains gel-like ⇒ movement restricted

Other factors affecting fluidity:

Degree & type of acyl chain unsaturation ⇒ DB ↑ fluidity

Acyl chain length ⇒ long chains less fluid

Cholesterol content ⇒ ↑ fluidity

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14
Q

Membrane Lipid

Distribution

A

Differences in bulk lipid composition among various cell membranes.

Differences in lipid composition between two leaflets.

Includes different classes of lipids and breakdown of individual phospholipids.

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15
Q

Membrane Lipid

Assemetry

A

Asymmetry established during membrane biogenesis.

Maintained by specific lipid transporter proteins:

  • Flippases ⇒ move lipids from the outside to the inside face
    • Aminophospholipid translocase
      • transports PS and PE to inner leaflet
  • Floppases ⇒ move lipids from the inside face to the outside face
  • Scramblases ⇒ randomize lipids between leaflets
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16
Q

Lipid Rafts

A

Microdomains where specific lipids can be found.

  • 10-200 nm
  • Rich in cholesterol and sphingolipids
  • Longer acyl chains ⇒ thicker membrane
  • Rafts can move about and merge
  • Enrichment of certain proteins in lipid rafts facilitates activity
    • spatial proximity
    • altered lipid environment
    • Ex. GPI anchors and signal transduction receptors
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17
Q

Caveolae

A

Special type of lipid raft.

  • Small invaginations in plasma membrane
  • Cavolins localized here
    • lipid-modified membrane proteins that bind cholesterol
    • their presence leads to invagination
    • involved with endocytosis
    • involved with some signal transduction pathways
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18
Q

Creutzfeldt-Jakob Spongiform Encephalopathy

A

Caused by an infectious protein ⇒ prion

Prion is a GPI-anchored protein found in lipid rafts.

Internalization by macropinocytosis one of the initial steps in disease process.

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19
Q

Diffusion

Definition

A

The random movement of a molecule fueled by thermal energy of the normal kinetic motion of matter.

Continues until equilibrium is reached.

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20
Q

Simple Diffusion

A

Movement directly through the lipid bilayer.

Driven by the concentration gradient.

At equilibrium, molecules continue to cross the membrane but no net movement occurs.

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21
Q

Fick’s First Law of Diffusion

A
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22
Q

Partition Coefficient (K)

A
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23
Q

Permeability Coefficient (P)

A
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24
Q

Overton’s Law

A

Permeability of coefficients of solutes that have approx. the same diffusion coefficients depends directly on their partition coefficients.

Applies to small molecules ⇒ > 4-5 carbons

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25
Q

Restricted Diffusion

A

Channel proteins present in lipid bilayers that provide diffusional pathways.

Rates of diffusion of molecules strongly influenced by molecular size.

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26
Q

Clinically Relevant Transporter

Examples

A
  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
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27
Q

Facilitated Diffusion

A

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
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28
Q

GLUT1

A
  • Found in RBC and vascular epithelium
    • Including BBB
  • Transports:
    • D-glucose ⇒ Km = 1.5 mM
    • D-mannose
    • D-galactose
  • Can discriminate between D-glucose and L-glucose
  • Deficiencies linked to seizures
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29
Q

GLUT4

A

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

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30
Q

GLUT5

A

Fructose transporter found in the small intestine.

Deficiencies linked to dietary fructose intolerance.

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31
Q

Ion Channels

A

Hydrophilic transmembrane pores.

Provides water-like environment for ion diffusion.

Does not require a conformational change ⇒ extremely rapid ⇒ approaches diffusion rate in water

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32
Q

Primary Active Transport

A

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
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33
Q

Post-Albers Cycle

A

Representative of all transporters that use ATP

E1 and E2 conformations:

Selectively binds a different ion

Promotes its translocation across the membrane

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34
Q

P-Type Transporters

A

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)
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35
Q

Na+/K+-ATPase

(Na+ pump)

Characteristics

A

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
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36
Q

Na+/K+-ATPase

Role in Osmotic Balance

A

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
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37
Q

Ca2+-ATPase

(Ca2+ pump or SERCA)

A

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
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38
Q

H+/K+-ATPase

(Proton pump)

A

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
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39
Q

F- and V-Type Transporters

Mechanism

A

Follows Post-Albers Cycle mechanism.

E1 and E2

No phosphorylated intermediate.

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40
Q

F-Type Pumps

A

Found in mitochondria and chloroplasts.

Run “backwards”

Synthesizes ATP in oxidative phosphorylation and photophosphorylation

Uses movement of H+ down its concentration gradient

41
Q

V-Type Pumps

A

Found in intracellular organelles such as lysosomes.

Pump proteins into organelles to acidify intraorganelle environment.

42
Q

ATP-Binding Cassette (ABC)

Transports

A
  • Large family of ATPases
  • All contain a highly conserved ATP binding cassette
  • Clinically important
  • Includes:
    • MDR transporter
    • CFTR
    • ABCA1 cholesterol transporter
43
Q

Multidrug Resistance (MDR)

Transporter

A
  • Class of ABC transporter
  • Responsible for extrusion of cationic hydrophobic metabolites and drugs
  • Expression ↑ by exposure to substrate
44
Q

Cystic Fibrosis Transmembrane Regulator

(CFTR)

A
  • Class of ABC transporter
  • Responsible for Cl- secretion by some epithelial cells
    • pulmonary tree
    • pancreas
    • sweat glands
  • Deficiencies causes cystic fibrosis
45
Q

ABCA1 Cholesterol Transporter

aka

Cholesterol efflux regulatory protein (CERP)

A
  • Moves cholesterol and phospholipids to lipid-poor lipoproteins
  • Major role in lipid homeostasis
  • Defects cause Tangier disease
    • see ↓ [HDL]
46
Q

Secondary Active Transport

A

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
47
Q

Cotransport

A

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
48
Q

Na+/glucose Cotransporter

(SGLT1)

A
  • 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
49
Q

Na+/K+/2Cl- Cotransporter

A
  • Found in a wide variety of cells
    • Thick ascending limb of the loop of Henle
      • Important in urine formation
  • Inhibited by Furosemide
50
Q

Countertransport

A

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
51
Q

Na+/Ca2+ exchanger

A

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
52
Q

Na+/H+ exchanger

A

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
53
Q

Cl-/HCO3- exchanger

A

Couples countertransport of Cl-and HCO3-.

AE1 important for transporting HCO3- into RBC in the lung and out of the RBC in the periphery.

54
Q

Mitochondrial ADP/ATP exchanger

A

ATPmitochondrial matrix ↔︎ ADPintermembrane space

Allows oxidative phosphorylation to continue.

Delivers ATP to cytoplasm for use by cells.

55
Q

Osmosis

A

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.

56
Q

Osmotic Pressure

(∆π)

A

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

Driving force for osmosis.

57
Q

Cellular

Osmotic Pressure

A

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
58
Q

Osmolarity

A

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

59
Q

Reflection Coefficient

(σ)

A

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

60
Q

van’t Hoff

Equation

A

Defines the osmotic pressure of a solution:

61
Q

Tonicity

A

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

62
Q

Aquaporins

A

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
63
Q

Renal Aquaporins

A

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
64
Q

Membrane Potential

(Vm)

A

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.

65
Q

Requirements for a Membrane Potential

A
  1. concentration gradient
  2. selective membrane permeability
66
Q

Nernst Equilibrium Potential

(Ex)

A
67
Q

Nernst Potential

Physiological Equation

A
68
Q

Ionic

Driving Force

A

Net driving force proportional to the difference between membrane potential and ion’s equilibrium potential.

Vm - Ex

When net driving force ≠ 0 ⇒ net flux occurs.

Direction given by sign of (Vm - Ex)

Vm can typically be manipulated by applying external voltage across the membrane ⇒ creates driving force for ion.

69
Q

Goldman-Hodgkin-Katz (GHK)

Equation

A
70
Q

Leak Pathways

A

Non-gated ion “channels” selective for particular ions

Always in an open state

Ex. Two pore K+ channel ⇒ K2P

71
Q

Na/K-ATPase

Membrane Potential

A

3 Na+ out ↔︎ 2 K+ in

Net movement of one ⊕ charge out

Contributes ~ -5 mV to Vm

72
Q

Cl- Balance

A

Passively distributes itself across the membrane in response to Vm

ECl = Vm

Relative ⊖ charge inside the cell inhibits Cl- movement into cytosol

73
Q

Action Potential

Mechanism

A

Membrane depolarized to threshold ⇒ action potential.

  1. Depolarization phase
    • Na+ channels open rapidly
      • Membrane is Na+ selective
      • Vm ≈ ENa
    • K+ channels have not opened yet
  2. Repolarizaton phase
    • K+ channels open
    • Na+ channels inactivated
    • Vm approaches EK
  3. Hyperpolarization phase
    • K+ channels still open
    • Na+ channels closed and inactivated
    • Vm equals EK
  4. Return to resting state
    • Both K+ and Na+ channels have reset
    • Only K+ leak channels open
    • Vm approximately equal to EK
74
Q

Action Potential

Membrane Permeability Cycle

A
75
Q

Absolute Refractory Period

A

Time during which an action potential cannot be elicited regardless of the stimulus.

Due to fact that Na+ permeability has inactivated.

76
Q

Relative Refactory Period

A

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.

77
Q

Effective Refractory Period

A

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.

78
Q

Endocrine Signaling

A

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

79
Q

Paracrine Signalling

A

Signalling molecule interacts with receptors on a neighboring cell.

Ex. neurotransmission

80
Q

Autocrine Signaling

A

Cells respond to a molecule they produced.

Ex. T lymphocytes produce IL-2 to stimulate their own proliferation.

81
Q

Intracellular Receptors

A
  • 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
82
Q

Cytoplasmic Receptors

A
  • 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
83
Q

Intranuclear Receptors

A
  • 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
84
Q

Cell Surface Receptors

A

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
85
Q

Ligand-Gated Ion Channels

A
  • Liganding binds forms a selective pore in the membrane
  • Alters transmembrane potential
    • Excitatory receptors ⇒ depolarization
    • Inhibitory receptors ⇒ hyperpolarization
  • Very fast signaling
86
Q

Enzyme-linked Receptors

A
  • 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)
87
Q

Receptor Tyrosine Kinases

(RTK)

A
  • 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.
88
Q

Insulin Receptor Signaling

A
  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
89
Q

Cytokine Receptors

A
  • 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
90
Q

G-Protein Coupled Receptors

(GPCRs)

A
  • 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
91
Q

G-proteins

Overview

A

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
92
Q

G Proteins

Mechanism

A
  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
93
Q

GS Proteins

A

Stimulates adenylyl cyclase.

Examples:

β-adrenergic receptors

Glucagon receptors

TSH receptors

94
Q

GI Proteins

A

Inhibits adenylyl cyclase.

Examples:

α2 adrenergic receptors

M2 muscarinic receptors

95
Q

Gs or GI

Pathways

A

Gs stimulates and GI 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.

96
Q

Hepatic Glycogen Catabolism

Control

A

Epinephrine ↔︎ β-adrenergic receptors

Glucagon ↔︎ glucagon receptors

Both are GS receptors.

⊕ adenylyl cyclase ⇒ ↑ [cAMP] ⇒ ⊕ PKA

PKA activates glycogen phosphorylase and inhibits glycogen synthase.

Results in increased glycogenolysis.

97
Q

GQ Protein

A

Activates phospholipase C.

Works via IP3/DAG system.

Examples:

α1 adrenergic receptors

M1 muscarinic receptors

Angiotensin II type 1 receptors

98
Q

IP3/DAG System

A
  1. Ligand binds GPCR and resulting in GQ activation
  2. GQ 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

Molecules to Organs (12 decks)

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