Hormonal Control Of Metabolism

Front 1

3 rapidly acting hormones

Back 1

insulin

glucagon

epinephrine/norepinephrine

Front 2

2 slowly acting hormones

Back 2

cortisone/hydrocortisone

thyroid hormone

Front 3

Insulin's hormonal "message" is _______.

Back 3

Glucose and amino acids are presently available, more on on the way.

Front 4

Glucagon's hormonal "message" is _______.

Back 4

Glucose is in short supply.

Front 5

Epinephrine/norepinephrine's hormonal "message" is ______.

Back 5

Glucose demand is expected to rise sharply on short notice (short term stress).

Front 6

Cortisone/hydrocortisone's hormonal "message" is _______.

Back 6

Demand for glucose is likely to remain high over extended period (long-term stress).

Front 7

Thyroid hormones' hormonal "message" is _________.

Back 7

Metabolic rate should be increased.

Front 8

Insulin, glucagon and other peptide hormones are produces in the _________ in the _______. Secretion responds to _______ levels in the blood. Secretion is affected by early signals of ________.

Back 8

Islets of Langerhans in the pancreas

glucose levels

nutrient availability

Front 9

_________ is lack of insulin secretion due to destruction of pancreatic islet beta-cells.

Back 9

Type I diabetes mellitus

Front 10

_________ is lack of insulin EFFECT on target cells - insulin levels are often increased. There is some therapeutic benefit from further stimulation of insulin secretion.

Back 10

Type II diabetes mellitus

Front 11

Insulin secretion in the pancreatic beta-cell is triggered by membrane _________.

Back 11

Depolarization

Front 12

Insulin has 2 inactive precursors, _____ and ______.

Back 12

preproinsulin, proinsulin

Front 13

When preproinsulin is cleaved in the ER, the _____ is removed. When proinsulin is cleaved in the Golgi apparatus, the _____ is cleaved, then secreted along with the insulin in ______ that undergo exocytosis.

Back 13

signal peptide

C-peptide

granules

Front 14

The insulin receptor is a _________________. It first _____ itself and then a series of insulin receptor ____. The first phosphorylation locks the receptor in its active conformation, and the others trigger intracellular event cascades.

Back 14

receptor tyrosine kinase

phosphorylates itself, then a series of insulin receptor substrate proteins

Front 15

_____________ promotes sugar uptake by increasing the number of surface-exposed glucose transporters.

Back 15

Insulin

The glucose transporters normally stored in vesicles move to the cell surface.

Front 16

______ and ________ act by G-protein-coupled receptors.

Back 16

Glucagon and epinephrine.

Front 17

What effect does protein kinase A have on hormone sensitive lipase?

Back 17

Increases activity of hormone sensitive lipase.

Fatty acids will be mobilized as alternative sources of energy - for either direct (muscle) or indirect use (ketone bodies for brain, other organs).

Front 18

What effect does protein kinase A have on glycogen synthase?

Back 18

DECREASES activity of glycogen synthase.

Glucose remains immediately available because it isn't locked up in glycogen.

Front 19

What effect does protein kinase A have on phosphorylase kinase?

Back 19

INCREASES phosphorylase kinase, which in turns increases glycogen phosphorylase.

Glucose is released from glycogen storage (if available).

Front 20

What effect does protein kinase A have on PFK-2/Fructose-2,6-bisphosphatase?

Back 20

(PFK-2 and Fructose-2,6-bisphosphatase are part of one bifunctional enzyme)

PKA inhibits PFK-2, lowering amount of fructose-2,6-bisphosphate formed

PKA activates Fructose-2,6-bisphosphatase so more fructose-2,6-bisphosphate is broken down

fructose-2,6-bisphosphate is an activator of PFK-1 (glycolysis) so glycolysis will not be favored; fructose-1,6-bisphosphatase (gluconeogenesis) is activated

Front 21

Insulin _____ the activity of protein kinase A. PKA phosphorylates Acetyl-CoA carboxylase and pyruvate dehydrogenase, which ______ them. This means that acetyl-CoA is diverted to form ______.

Back 21

increases activity of PKA

inhibits

lipid formation

Front 22

How does fructose 2,6-bisphosphate prevent a futile cycle?

Back 22

This regulatory molecule increases the activity of PFK1 (glycolysis) and inhibits the opposing enzyme (FBPase1) in the reverse pathway (gluconeogenesis) so that the synthesis of glucose is not taking place in the same cell where glucose is being broken down (a futile cycle).

Front 23

How does the release of insulin or epinephrine affect the activity of PFK-2/Fructose-2,6-bisphosphatase?

Back 23

PFK2 and FBPase2 form, or hydrolyze, respectively, fructose 2,6-bisphosphate, that controls phosphofructokinase-1 (glycolysis).

Front 24

Primary structure of insulin

Back 24

an A chain and a B chain, derived from a common precursor that undergoes site-specific cleaveages; insulin and the C peptide are both stored in vesicles and released together.

Front 25

Problem with animal insulin?
What do we use instead?

Back 25

Sequence variations from human insulin to bovine to porcine, so it is possible to develop antibodies against nonhuman insulins - usually use recombinantly produced human insulin.

Front 26

3-step mechanism for secretion of insulin from beta-cells

Back 26

1)glucose enters & is degraded to yield ATP

2)ATP binds to the sulfonurea receptor, closing the KirK+ channel & depolarizing the membrane

3) Depolarization opens voltage-gates Ca++ channels & allows Ca++ into cell - triggers insulin secretion by exocytosis

Front 27

________ is the target of sulfonylurea derivatives like tolbutamide that mimic the effect of ATP on the receptor, stimulating the release of insulin. It is used in therapy for __________.

Back 27

Sulfonylurea receptor

Type II diabetes

Front 28

The insulin receptor is a __________ in the cytoplasmic membrane. Its ______ domain binds insulin, and its ______ domain is a protein tyrosine kinase.

Back 28

transmembrane protein

extracellular

intracellular

Front 29

Ligand-activated insulin receptors first perform _____ and the phosphorylate a series of intracellular proteins called __________.

Back 29

mutual phosphorylation

insulin receptor substrates (IRS)

Front 30

4 intracellular effects of insulin ...

Back 30

1) activation of glycogen synthesis by indirect deactivation of glycogen synthase kinase

2)mediation of transcriptional effects of insulin - increases rate of transcription for glycolysis and TAG synthesis

3)increase of cellular glucose uptake by moving glucose transporters from intracellular vesicles to the membrane

4)activation of phosphodiesterase, lowering cAMP levels to counter effects of epinephrine and glucagon

Front 31

Stimulation of glycogen synthesis by insulin:

4 steps

Back 31

1) receptor phosphorylates IRS-1

2) IRS-1P binds to and phosphorylates membrane lipid PIP2 (phosphatidylinositolbisphosphate-3-kinase) to PIP3 (triphosphate)

3)PIP3 activates PKB, which phosphorylates glycogen synthase kinase 3

4) glycogen synthase kinase 3 is less active when phosphorylated so phosphorylates glycogen synthase LESS so glycogen synthase is MORE active

Front 32

Insulin induction of enzymes for glycolysis:

3 steps

Back 32

1)receptor phosphorylates IRS-1, which binds to Grb-2

2) Grb-2 forms complex with Sos and Ras, exchanging GDP bound to Ras for GTP; this activates a protein kinase Raf-1

3) 2 more protein kinases - MEK & MAPK - phosphorylated in turn. MAPK acts on nuclear transcription factors & increases rates of transcription for genes for glycolysis enzymes and TAG synthesis

Front 33

Insulin increase of cellular glucose uptake.

Back 33

Translocatiion of GLUT4 receptors:

1) IRS-1 phosphorylates PIP2
2) PIP3
3) PKB, phosphorylates cytoskeletal proteins

GLUT4 is also moved to cell surface by vesicle fusion

Front 34

Glucagon and epinephrine's metabolic effects are ______ to each other and _____ to insulin. Glucagon is mainly concerned with _________, while epinephrine also affects the ___ and _____. Both use __________ receptors.

Back 34

similar to each other

antagonistic to insulin

glucagon - metabolic regulation

E - heart rate, blood pressure

Both use G-protein-coupled receptors (GPCR)

Front 35

Signal transduction by a GPCR

Back 35

1) when ligand binds, conformational change of both receptor and G protein

2)change exchanges GDP for GTP on the alpha-subunit of the G-protein

3)When GTP is bound the alpha-subunit dissociates and binds to the effector protein

4)later, GTP'ase that is built into the alpha-subunit cleaves GTP to GDP

5) cleavage of GTP makes alpha-subunit revert to inactive conformation & re-associate with beta and gamma subunits

Front 36

Both the epinephrine receptor and the glucagon receptor are coupled to the same G protein. It binds to _______ as its effector protein & activates it to make ______, which binds to ____ causing the 2 regulatory (R) subunits to release the catalytic subunits.

Back 36

adenylate cyclase

cAMP

protein kinase A > tends to sustain or increase blood glucose levels

Front 37

4 major effects of cortisol:

Back 37

1)stimulates protein breakdown mostly for gluconeogenesis

2)increases enzyme activity for glycogen synthesis AND breakdown, and for gluconeogensis

3) Increased sensitivity to E and NE

4) suppresses pain & inflammtion by inhibition of prostaglandin synthesis