BC 25 Metabolic Signalling Flashcards Preview

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Flashcards in BC 25 Metabolic Signalling Deck (19):
1

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


2

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

3

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

4

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)

5

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

6

Insulin and Glucagon (P) states

Insulin Favors DEphosphorylation

Glucagon (or epinephrine) favors Phosphorylation

7

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

8

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

9

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

10

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,

11

Glucagon

ONLY LIVER
-glucose synthesis and release from liver
-ketone bodies alternate source to FA's

-Glucose for brain /RBC's

12

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

13

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

14

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

15

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)

16

MUSCLE CELL

Insulin Receptor
-HIGH IG
-ampK mobilize Glut4 to membrane
-glycogenesis for muscle use
-inhibits muscle breakdown to amino acids for liver




Epinephrine
-stress
-muscle glycogen breakdown to glucose

17

Atkins/low carb

protien thing

18

AMPK

Fuel gage

-AMP-lowest energy molecule
-if AMP high, need more energy (ATP)
-AMPK activated
-stimulates use of FA and glucose for Energy and slowes energy expensive pathways (in muscle can translocate glut 4 to membrane)

HIGH AMPK
-ATP producing pathways
-glycolysis, B ox, glucose uptake

inhibits ATP consuming pathways
- FA snthesis
-cholesterol synthesis
-glycogen synthesis
-protein synthesis


think about working out before eating


-diabetes and adipokines?

19

Metformin

Type II diabetes drug

inhibits teh ATP synthesis machinery in mito. Increase levels of intracellylar AMP and AMPK activation

-in insulin resistant patients has been shown to reduce plasma glucose
-decrease inappropriate liver guconeogenesis ( atp expensive)
-sitm GlUT 4 glucose uptake in muscle.

-promotes B ox of lipids, rather than synth or storage. Reduce circulating TAG levels an dimpove insulin sensitivity