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PHRD5015 Mechanisms of Disease - Module 2 (Signaling in the Multicellular Environment)
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G protein bound to
1 adrenergic receptors
Gs
G protein bound to
2-adrenergic receptors
Gq
activates PLC
Gq
hormone that increases cardiac myocyte contractility
norepinephrine
cleaves phosphatidyle inositol (PIP3)
PLC
DAG
remainder of PIP3 in the membrane after cleavage
ligand for Ca2+ channels on ER
inositol triphosphate (IP3)
activates PKC
PLC
localizes PKC to membrane
DAG
2 requirements for PKC activation
1) DAG
2) Ca2+
result of coupling
2 adrenergic receptors to Gi
inhibition of adenylate cyclase
P/S NS NT
ACh
P/S NS receptors
muscarinic receptors
G protein bound to mAChR
Gq
central regulator of smooth muscle tone
Ca2+ levels
sympathetic signal targets
smooth muscle
parasympathetic signal targets
vascular epithelium
mediates activation of NOS
ACh
eNOS activator
calmodulin
activates the production of vascular smooth muscle cGMP
endothelial NO
cGMP effect on smooth muscle cells
promotes relaxation by opposing Ca2+
3 stages of angiogenesis
1) initiation
2) invasion
3) maturation
2 regions of ECM
1) basement membrane
2) interstitial matrix
proteins constituting basement membrane
type IV collagens
laminins
fibronectic
proteins constituting interstitial matrix
fibrillar collagens
proteoglycans
glycoproteins
link cell to ECM
integrins
activate focal adhesion kinase (FAK)
integrins
signal for the growth of new blood vessels
hypoxia
HIF-1
TF induced in any cell in response to decreased O2
prolyl hydroxylase (PHD)
hydroxylates HIF-1
under normoxic conditions
PHD cofactor
O2
activates VEGF transcription
HIF1
-primary receptor mediating angiogenesis
-RTK consisting of 2 identical subunits
VEGFR2
angiogenesis mediating receptor that promotes the activation of PLC
and PI3K
VEGFR2
how PKC activates MAPK cascade
via Raf-1
docking site for PKC
DAG
overexpresses VEGFR2 (and suppresses expression in surrounding cells)
tip cell
high expression of Hes, Hey, VEGFR1
stalk cells
membrane protein that serves as a ligand for Notch and cleaves it upon binding
Dll4
PI3K promoted VEC migration mechanism
VEGFR2 activates PI3K -> P-Akt -> actin monomer polymerization
respond to absolute concentration of VEGF (tip vs stalk)
stalk cells
cells that render the vascular tube VEGF independent & seal it
pericytes
condition in which new blood vessels are pericyte poor
diabetic retinopathy
secreted by pericytes
TGF
secreted enzymes that break down ECM components
matrix metalloproteinases (MMPs)
endogenous factor inhibiting angiogenesis
fragments of collagen IV
(bind & inhibit integrin signaling)
H responsible for storing energy during times of feeding
insulin
H responsible for mobilizing energy during times of fasting
glucagon
insulin sensitive glucose transporter
GLUT4
rate limiting step in glucose storage and glucose utilization
glucose uptake
glucose is immediately converted to ____ upon uptake in cell
glucose-6-phosphate
substrate for insulin RTK
IRS1 (insulin receptor substrate 1)
docking site for PI3K via its SH2 domain
phosphorylated site on IRS1
pathway for PI3K promotion of vesicle fusion
insulin -> p-insulin RTK -> p-IRS1 -> PI3K -> IP2 converted to IP3 -> PDK docks at IP3 -> p-Akt -> exocytosis of GLUT4 for surface deposition
pathway for gluconeogenesis inhibition by insulin
insulin -> p-Akt -> p-FOXO1 (p inhibits)
-breaks down fat into FA and glycerol for uptake
-stimulated by insulin
LPL - lipoprotein lipase
-breaks down triglycerides in adipocytes for use
-inhibited by insulin
HSL - hormone sensitive lipase
glucagon/cAMP regulation
glucagon -> glucagon receptor -> Gs -> AC -> cAMP -> active PKA
5 functions of Akt
1) increase glycogen synthesis
2) increase FA and triacyl glycerol synthesis
3) decrease gluconeogenesis
4) decrease lipolysis
5) increase glucose transport
insulin proliferation pathway
insulin receptor -> Shc -> Grb/SOS -> Ras -> MAPK -> proliferation
inhibits glycogen synthase
glycogen synthase kinase
AMPK activators (4)
1) hypoxia
2) ischemia
3) heat shock
4) exercise
AMPK inhibits.. (3)
1) adipose FA synthesis
2) hepatic gluconeogenesis
3) mTOR
enzymes which modify other proteins
sirtuins
-enzyme that is a key metabolic sensor in tissues associated with metabolism regulation
-NAD+ dependent
SIRT1
electron acceptor
NAD+
electron donor
NADH
energy deficit if NAD+ levels are ____
high
deacetylates FOXO1 and PGC1
to activate them
SIRT1
involved in gluconeogenesis enzyme transcription
FOXO1
involved in FA oxidation enzyme transcription
PGC1
Author
daynuhmay
ID
235129
Card Set
PHRD5015 Mechanisms of Disease - Module 2 (Signaling in the Multicellular Environment)
Description
Mechanisms of Disease
Updated
2013-09-16T18:51:23Z
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