Biochem: Module 5

Front 1

APO-B100

Back 1

VLDL
IDL
LDL

Front 2

APO-A

Back 2

HDL

Front 3

APO-C

Back 3

Chylomicrons

Front 4

Gas

Back 4

beta-adrenergic amines, glucagon, PTH

Front 5

Gai
Gaq

Back 5

alpha-adrenergic amines, NT, Ach

Front 6

Gat (mechanism)

Back 6

Rhodopsin[=] light

increase cGMP phosphodiesterase

increase cGMP

ion channels close

Front 7

Intrinsic TK receptors

Back 7

EGF, IGF-1/2, insulin

Front 8

Non-intrinsic TK receptors

Back 8

GH, prolactin cytokines

Front 9

Cytokine Trasnduction system

Back 9

non-intrinsitc TK rec.

(w/ GH and prolactin)

Front 10

Insulin Transduction system

Back 10

Intrinsic TK Rec.

(w/ IGF-1/2, EGF)

Front 11

Signal Transduction System for Prolactin

Back 11

non-intrinsic TK rec.

JAK/STAT

-->STAT dimerizes to go to nucleus and act as a transcription factor

(also used by GH and cytokines)

Front 12

Signal transduction system for IGF-1/2

Back 12

same as for insulin and EGF

1. Intrinsic TK autophosphorylates
a. GRB-->Ras system-->MAP kinases
b. PLC-y-->IP3 + DAG ---> Ca2+ and PKC
c. PI3-K -->PIP2---(phosphorylation)-->PIP3 ---> protein kinase cascade

Front 13

Signal Transduction System for Intrinsic TK rec.

Back 13

(IGF-1/2, EGF, insulin)

1. PLC-->IP3 + DAG --> Ca2+ and PKC

2. Grb--> Ras system-->MAP kinases

3. PI3-K-->PIP2--(phorphorylation)-->PIP3----->protein kinase cascade

Front 14

Natiuretic Peptide Signal Transduction Pathway

Back 14

Guanalate Cyclase activation-----> increased cGMP----> activatio nof PKG

Front 15

3 ways a G-PCR can be inactivated

Back 15

1. ligand stops bonding to receptor

2. GTPase binds Ga[=]GDP

3. phosphorylate the cytoplasmic side of the G-PCR--> G-PCR[=] beta-arrestin, and inactivate regardless of ligand binding

Front 16

beta-arrestin

Back 16

will bind to phosphorylated G-PCR and inactivate regardless of ligand binding

Front 17

SRIF

Back 17

Somatotrophin

decreases released GH from anterior pituitary

Front 18

GH biological actions (general)

Back 18

-->insulin resistance
stimulate lipolysis and FFA oxidation, stimulate liver gluconeogenesis, inhibits muscle glucose uptake

-->anabolic
stimulate bone growth, protein synthesis, soft tissue growth

Front 19

GH actions (Biochemical)

Back 19

-->diabeteogenic
increase acetoacyl CoA, citrate, and ATP--> activate pyruvate decarboxylase

--->increase Acetoacyl CoA, citrate, and ATP----> decrease PFK-1 and pyruvate dehydrogenase-------> increase glucose-6-phosphate------> decrease hexokinase

Front 20

GH actions on:
Pyruvate dehydrogenase

Pyrivate decarboxylase

Back 20

Pyruvate dehydrogenase--> decreased (along with PFK-1)

Pyruvate decarboxylase---> increase activity

Front 21

How GH decreases Glycolysis:

Back 21

increase Acetoacyl CoA, citrate, and ATP

decrease PFK-1 and pyruvate dehydrogenase

increase glucose-6-phosphate

decrease hexokinase

Front 22

Laron's Syndrome

Back 22

-->resistance to GH

-->treat with IGF-1

Front 23

IGF-1 Effects

Back 23

--> stimulates muscle glycolysis
-->increases muscle uptake of insulin
-->stimulates protein synthesis, bone, muscle cartilage

(insulin-like metabolic effects and growth promotion of GH)

***liver and adipose tissue have very few IGF-1 Receptors***

Front 24

Excessive Production of GH (Causes and Treatment)

Back 24

1. Gigantism and Acromegaly--> commonly a mutation in Gas (rec. for GnRH) constitutively turning on GH production

2. Laron's Syndrome-->resistance to GH (treat with IGF-1)

Front 25

GH Deficiency (Causes and Treatment)

Back 25

-->mutations in GnRH or receptor, pituitary damage

--> Diagnostic: low serum GH, low serum IGF-1//2
***response to GH still intact***

-->give GH (but be damn sure that's what it is)

Front 26

Type II-Diabetes and GH/IGF

Back 26

-->never give GH

-->can give IGF

Front 27

Catabolic Illnesses/ Negative Nitrogen balance and GH/IGF

Back 27

-->administer both GH and IGF

-->full anabolic affects with glucose effects offset

Front 28

Ostopenia / osteoporosis and GH/ IGF

Back 28

-->IGF will assist PTH in bone deposition

Front 29

Detection of exogenous GH and abuse

Back 29

-->GH released in pulsitile manner

-->better to judge IGF-1 and IGFBP3

-->local gene injection makes impossible to detect due to localized response (no serum elevation)

Front 30

Cholesterol synthesis

Back 30

Acetyl CoA <-----all carbons from here

Acetoacyl CoA

HMG-CoA

Melvatonate

Isopentyl PPi

2x Isopentyl PPI --->> Dimethyl Phosphate

Dimethyl Phosphate + 2x Isopentyll PPI ---> Farnestryl PPI

2x Farnestryl PPI--->Squalene

Squalene + O2 --->Lanosterol

CHolesterol

Front 31

Commited Step in CHolesterol SYnthesis

Back 31

HMG-CoA -----(HMG Reductase)----> Melvalonate

Front 32

Regulation of HMG-Reductase

Back 32

1. SREBP moves from ER to nucleus to activate HMG transcription when cholesterol low

2. Membrane portion of HMG-Reductase will change conformation to activate proteolytic destruction when cholesterol metabolites high

3. Activity decreased by AMP-active Kinase (phosphorylation)

Front 33

Statins

Back 33

-->HMG-Reductase inhibitor

-->will increase LDL receptors

Front 34

Bile Salt synthesis

Back 34

Cholesterol ---(7a-hydroxylase--> 7a-Cholesterol

7a-cholesterol---(P450 monooxidases)-->Cholyl CoA

Cholyl Co will join with
1. Glycine---> Glycocholate (major product)
2. Taurine----> Taurocholate (minor product)

Front 35

List in order intermediates of cholesterol biosynthesis

Back 35

Acetyl CoA
Acetoacyl CoA
HMG-CoA
Melvalonate
Isopentyl PPI
Dimethyl Phosphate
Farnesrtyl PPi
Squalene
Lanosterol
Cholesterol

Front 36

Structure of bile salts

Back 36

detergents

-->amphipathic
-->solublize dietary lipids

-->same structure but the carbon tail has hydrophilic tail

Front 37

Cholesterol esters

Back 37

-->less soluble than cholesterol
-->more easily transported in lipoproteins, stored in liver

LCAT-->HDL
ACAT-->liver

Front 38

Cellular uptake of cholesterol

Back 38

(LDL)-APO-B100[=] clathrin-coated pits

endocytosis-->fusion with lysosome--> degredation

released unesterified cholesterols
1. used in membrane synthesis
2. ACAT will esterify for storage or VLDL synthesis (liver)

***LDL receptor returned to membrane****

Front 39

Internalized Cholesterol Effects on Regulation

Back 39

1. Decreases HMG-Reductase activity

2. Decrease LDL Recepor synthesis via inhibition of mRNA

3. Activation of ACAT

Front 40

Structure of LDL Receptor

Back 40

-->cyteine-rich residues = LDL-binding domain

-->homologous EGF domains and 6 blades of transducin units

-->O-linked glycosylated region= stablized rec. in membrane

-->hydrophopic (mem. region) and cytoplasmic tail (interacts with clathrin)

Front 41

Effects of ADH on target tissues (with rec)

Back 41

ADH [----Gas-PCR------] principle cells (collecting ducts)
---->increase Aquaporin-2 synthesis

ADH [-----Gaq-PCR-----] vascular smooth muscle
--->vasoconstriction

Front 42

Angiotensin II on target tissues (with rec.)

Back 42

AngII [-----Gq-PCR------] vascular smooth muscle
----->vasoconstriction

AngII [----Gq-PCR----] Zona Glomerulosa
-->secretion of Aldoseterone (increase Na+ absorption)

Front 43

ANP/ ANF on target tissues with rec.

Back 43

ANF [-----Guanalate Cyclase----] vascular smooth muscle
-->vasodilation

ANF[-----Guanalate Cyclase----] Zona Glomerulosa
-->decrease Aldosterone secretion