Biochem 6 - Platelets, Endothelial Cells, Mitochondrial Function

Front 1

knockout mice and COX2

Back 1

inhibiting COX2 prevented polyps

Front 2

which prostaglandin protects intestinal mucosa

Back 2

PGE

Front 3

ACE inhibitors (3)

Back 3

Captopril
Enalopril
Ramipril

Front 4

what do endothelial cells do on their surfaces

Back 4

1. ATPase and 5'nucleotidase degrade ATP and ADP

2. inactivate PGE, PGF, LTC4, LTD4

Front 5

5 intracellular activities of endothelial cells

Back 5

1. MAO (decreases plasma monoamines). because NE is vasoconstrictor

2. activated state: thromboplastin synthesis and secretion to initiate clotting

3. resting state: plasminogen activator synthesis and secretion to initiate clot fibrinolysis

4. resting: prostacyclin (PGI2) production

5. EDRF (vasodilator)

Front 6

activated state of endothelial cells

Back 6

pro-inflammatory
pro-coagulant

Front 7

pathway with plasminogen activator

Back 7

resting endothelial cell produces plasminogen activator

this is a serine protease that cleaves plasminogen (which is incorporated into the clot) into plasmin

plasmin is a serine protease that breaks down fibrin

Front 8

CO and plasminogen activator

Back 8

CO inhibits endothelial plasminogen activator production

therefore inhibits fibrinolysis

Front 9

CO and cigarette smoke

Back 9

CO damages endothelial cell
prevents the resting endothelial cell from fibrinolysis
promotes clotting

Front 10

thrombophilia

Back 10

pro-clotting state

Front 11

role of heparin

Back 11

produced by mast cells
removes thrombin

Front 12

role of citrate and oxalate

Back 12

complex with Ca
coagulation proteins want to use Ca

Front 13

effect of prostacyclin on platelet aggregation

Back 13

inhibits

Front 14

prostacyclin letter number code

Back 14

PGI2

Front 15

pathway on page 8 (both)

Back 15

ok

Front 16

role of resting endothelial cells

Back 16

prevent thrombosis

Front 17

precursor for EDRF

Back 17

arginine

Front 18

how is PGI2 (prostacyclin) production inhibited

Back 18

COX2 inhibitor

Front 19

Vioxx AKA

Back 19

rofecoxib

Front 20

EDRF AKA

Back 20

NO

Front 21

mechanism of action of NO

Back 21

1. ACh binds to muscarinic receptor on endothelial cell

2. EDRF/NO is made from arginine

3. diffuses to smooth muscle (quickly because it is a radical so it has a short half life)

4. in smooth muscle it increases cGMP

5. cGMP results in smooth muscle relaxation

Front 22

what catalyzes the rxn of arginine to NO

Back 22

nitric oxide synthase (NOS)
analogous to:
NADPH:P450 monooxygenase

Front 23

cofactors (/side rxns) of NOS

Back 23

NADPH -> NADP+
O2 --> H2O

Front 24

steps of NO production

Back 24

L-arginine
N-OH-arginine
L-citulline + NO

each step also involves NADPH -> NADP+ and O2 -> H2O

Front 25

3 uses of nitroglycerin

Back 25

angina
HT
vasodilation

Front 26

adverse effects of nitroglycerin

Back 26

oxidative stress
headache unless tolerance

Front 27

how does tolerance develop to nitroglycerin

Back 27

vascular ALDH in mitochondria reduces NG to activate it
ALDH is inactivated by peroxynitrite
peroxynitrite is formed when NO reacts with superoxide radical

Front 28

2 NO generators (used for vasodilation)

Back 28

amyl nitrite
nitroglycerin

Front 29

amyl nitrite AKA

Back 29

isopentyl nitrite

Front 30

vasodilation in rectal mucosa (which drug)

Back 30

butyl nitrite

Front 31

what causes acute hemolysis in G6PD deficient individuals

Back 31

butyl nitrite

Front 32

amyl nitrite as a cyanide antidote

Back 32

nitrite oxidizes oxyhemoglobin to methemoglobin
Fe3+ of methemoglobin complexes cyanide

Front 33

3 uses of amyl nitrite

Back 33

1. Rx for angina
2. aphrodisiac
3. cyanide antidote

Front 34

Rx amyl nitrate route of admin

Back 34

inhaled from glass ampules that are enclosed in mesh and crushed in the fingers

Front 35

what reverses NG tolerance

Back 35

antioxidants
statins
carvediol
thiols
hydralazine

Front 36

which major pathways of metabolism occur in the cytosol (3)

Back 36

glycolysis
pentose phosphate pathway
fatty acid synthesis

Front 37

which 4 major pathways of metabolism occur in the mitochondrial matrix

Back 37

citric acid cycle
oxidative phosphorylation
beta oxidation of fatty acids
ketone body formation

Front 38

which 2 major pathways of metabolism involve interplay of both compartments

Back 38

gluconeogenesis
urea synthesis

Front 39

products of Citric acid cycle

Back 39

3NADH
FADH2
GTP
2H+
2CO2

Front 40

3 inhibitors of the citric acid cycle and what enzyme they act on

Back 40

see slide 4

halonate - succinate dehydrogenase
flurocitrate/fluroacetate/fluoroacetyl coA - aconitase
arsenite - alpha ketoglutarate dehydrogenase

Front 41

draw citric acid cycle from 2nd last page of notebook

Back 41

ok

Front 42

the citric acid is a source of biosynthetic precursors

Back 42

see slide 5

1. alpha keto-glutarate --> amino acids

2. succinyl coA ---> porphyrins

3. oxaloacetate --> amino acids
oxaloacetate --> Phosphoenol pyruvate ---> glucose

Front 43

oxaloacetate is sometimes used for generation of glucose and amino acids. how is oxaloacetate regeneration for continuation of the citric acid cycle

Back 43

from pyruvate

Front 44

how is the citric acid cycle regulated

Back 44

1. ATP
2. NADH
3. coA products
4. electron acceptors

see slide 6

Front 45

electron acceptor regulation of the citric acid cycle

Back 45

required for the last 4 steps of the citric acid cycle (except fumarate to malate)

Front 46

ATP regulation of the citric acid cycle

Back 46

pyruvate --> acetyl coA
acetyl coA to citrate
isocitrate --> alpha ketoglutarate

Front 47

coA and NADH regulation of the citric acid cycle

Back 47

acetyl coA and succinyl coA inhibit their own synthesis
these steps are also inhibited by NADH

Front 48

name of hypothesis that says that mitochondria evolved from anaerobic bacteria

Back 48

endosymbiont hypothesis

Front 49

endosymbiont hypothesis

Back 49

mitochondria evolved from anaerobic bacteria that were phagocytosed by eukaroytic cells at the time that oxygen appeared on earth

Front 50

mitochondria and bacteria are similar in that they both have

Back 50

cardiolipin
transporters
ribosomes
circular RNA and DNA

Front 51

2 drugs that should inhibit mitochondrial protein synthesis according to the endosymbiont hypothesis

Back 51

tetracycline
chloramphenicol

Front 52

what happens when tetracycline and chloramphenicol are used excessively

Back 52

bone marrow mitochondrial protein inhibition -> decreased production of WBCs, RBCs

intestinal epithelial cells stop dividing

Front 53

draw all the reactions on the last page of notebook

Back 53

ok

Front 54

complex 1

Back 54

NADH CoQ reductase

Front 55

complex 3

Back 55

cytochrome c reductase

Front 56

NADH CoQ reductase

Back 56

Complex 1

Front 57

cytochrome c reductase

Back 57

complex 3

Front 58

complex 4

Back 58

cytochrome oxidase

Front 59

cyochrome oxidase

Back 59

complex 4

Front 60

what happens at complex 4 (cytochrome oxidase)

Back 60

converts oxygen and water to H2O
pumps protons also

Front 61

2 components of complex 3

Back 61

cytochrome b
cytochrome c1

Front 62

blockers of the electron transport chain

Back 62

1. rotenone and amytal block Complex 1 --> QH2

2. antimycin blocks b1 --> c1

3. CN-, N3- and CO- block complex 4 --> O2

Front 63

cytochrome c catalytic site

Back 63

heme
Fe has 4 bonds to heme
1 bond to Methionine vis S atom
1 bond to His via N atom

heme itself is also bound to 2 cysteine residues

Front 64

fun fact about cyt c

Back 64

some of the residues have been invariant for millions of years
regardless of species or even kingdom
Met 80 and His 18 that coordinate Fe
and arginine and lysine clusters on the surface

Front 65

cytochrome c is responsible for electron transport AND

Back 65

major cause of most apoptosis is initiated by its release into the cytosol

Front 66

Last step in oxidative phosphorylation

Back 66

H+ gradient used to drive ATP synthase

Front 67

which 4 processes occur in the mitochondrion

Back 67

ketone body formation
oxphos
citric acid cycle
beta oxidation

Front 68

drug that is CN antidote

Back 68

amyl nitrite