BC 25 Metabolic Signalling Flashcards
Receptor Tyrosine Kinase
Insulin activated
-stimulates MapK via (auto-P)(GRB2)(SOS)(RAS-GTP)(RAF Kinase) (MAP KINASE)
- also stimulates: identical RTK recruits IRS-1 (Insulin receptor substrate 1) to activate (IRS 1 becomes phosphorylated)
- SH2 domain (Src homology 2) binds IRS-1 to RTK +GRB2 + PI3 Kinase
- PI3 (phosphotidyl inositol 3) Kinase activates PIP2 to become PIP3 (add one more phosphate
- PIP3 (TMP) activates cytoplasmic AKT
- GLUT4 brought to membrane (muslce and liver) (increase glycogen synthesis)
- Glycogen Synthase activated
PKA
activity stimulated by glyucagon/epinephrine
- increase phosphatase, promotes dephosphorylation of PKA
- increases insulin responsive cAMP Phosphodiesterase to decrease PKA activity
inhibited by insulin signalling
IRS1 PI3/AKT
IRS1 mediates activation of insulin stim pathways
-phophorylated
recruits GRB2 and PI3 kinase via SH2 domain
-Activates PI3
PI3/AKT
- GLUT 4 tranlocation to PM, mm & liver
- glycogenesis (m&l)
- protien phosphatase 1 (ppase 1) dephosphorylates PKA
Insulin effects
alter metabolic enzyme activity and promote cell division
- opposes teh action of clucagon by decreasing P of PKA sub
- increases protein P activity
- decreases PKA activity (phosphodiesterase)
Reciprocal Enzyme Regulation example
glucagon (GPCR) and insulin
LIVER
- Glycolysis: Pyruvate kinase active
- Gluconeogenesis: PKA shut down
Low IG ration= low insulin/high glucagon
-Pyruvate Kinase dephosphorylated (Active)
prevents enzymes in opposing pathways from being on at the same time
Insulin and Glucagon (P) states
Insulin Favors DEphosphorylation
Glucagon (or epinephrine) favors Phosphorylation
Hormones that Act with Glucagon
cortisol, epinephrine and norprinephrine
- insulin counterregulatory hormones
- cause the mobilization of fuels into the blood stream
- only Glucagon relieased in response to glucose levels
Epinephrine
Catecholamine NT: synthesized from tyrosine
Adrenal medulla: response to stresses (pain ex, hemorrhage, hypoxia, hypogly)
increaes glucagon release by panc alpha cells, decreases insulin from B cells. (lowers IG ratio)
-mobilization of macromolecules (glucose, FA) for oxidation
Insulin (tissue specific)
directs storage of dietary glucose as glycogen, storage of dietary TAG;s
LIVER:
-glucose enters goes to glycogen and FA
Adipocyte
-FA from liver plus glucose used to make triacylglycerols Tag’s
Muscle: Glucose stored as glycogen
Epinephrine (tissue Specific)
Decreases I/G ratio (direct on Panc cells)
PANCREAS:
- promotes glucagon exression
- inhibits Insulin expression
LIVER:
-promotes glucose mobilization from glycogen
-
ADIPOSE
-TAGs broken down to FA + Glycerol and mobilized (main source of E for liver, muscle adipo)
MUSCLE: promotes glycogen conversion to pyruvate and lactate (sent to liver)
epinephrineL flight or fight to stress: mobilization to prepare,
Glucagon
ONLY LIVER
- glucose synthesis and release from liver
- ketone bodies alternate source to FA’s
-Glucose for brain /RBC’s
HIGH IG Ratio Liver/adipose/muscle
FED/Absorbtive phase
major supplier of energy GLUCOSE
insulin stimulates activity of enzymes involved in glycolysis to TCA ETC
GLUCOSE ALWAYS BEING USED AS E SOURCE REGARDLESS OF IGG
LOW IG RATIO Liver/adipose/muscle
FASTING
-major supplier of evergy is FA
B oxidation of FA-> TCA (FADH2 GTP) ETC
Blood glucose maintained by BG from liver but reserved for brain and RBC
LIVER
Glucagon receptor
- low IG
- increase glucose secretin
- glycogenolysis (glycogen-glucose)
- gluconeogenesis (glucose synthesis)
Epinephrine Receptor
- Stress
- increase glucose secrection
- glycogenolysis (glycogen-glucose)
- gluconeogenesis (glucose synthesis)
Insulin Receptor
- High IG ration
- glycogenesis/lipogenesis
GLUT 2 (constitutive uptake)
Ketogenesis-livers uses no ketones, but can make them via FA oxidation
COMPARE TO DRAWN CHART
Adipose Cell
Insulin Receptor
- high IG
- activates GLUT 4 mobilization to membrane(ampK)
- helps make TAGs into FA storage
GlUT4
-FA synthesis
Epinephrine:
- stress
- FA mobilization (lipolysis of TAG’s)
