Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Toxicology > Mitochondrial Toxicity > Flashcards

Mitochondrial Toxicity Flashcards

1
Q

physiological function of ATP

A

supplying majority of ATP!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Functions common to most mitochondria

A 
ATP synthesis
terminal oxidationof pyruvate
beta oxidation of fatty acids
oxidation of acetyl CoA
fatty acid, protein and carbohydrate oxidations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

functions of some mitochondria

A

oxidation of branched amino chains, sulfate
nitrogen homeostatis, urea formation
activation of vit D3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

mitochondrial plasticity purpose

A

optimize energy production relative to demand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

physiological signals that could induce change

A

nutritional variations, different work loads, oxygen availability, developmental state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

example of plasticity with: nutritional value

A

urea cycle enzymes are increased by high protein diets and starvation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

example of plasticity with: different work load

A

volume density of mitonchondria in skeletal muscle change in association with aerobic activity so that ATP production and energy requirements are coordinated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

example of plasticity with: oxygen availability

A

mitochondrial enzymes decrease during chronic hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

responses to physiological signals are typically

A

reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Chemiosmotic Theory

A

describes the coupling of metabolic energy in the mitochondria
says that energy transducing membranes contain a proton pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

inner mitochondrial membrane contains

A

solute transport systems that function to allow the energy available from electron transport to be captured in the form of an electrochemical gradient which drives ATP synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

chemiosmotic proton pump model

A

H+ are pumped to the cytosol (which is the postive side)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

MAIN POINT of Chemiosmotic theory

A

the primary H+ pump generates such a high gradient of H+ that it forces the secondary pump to reverse and synthesize ATP from ADP and P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

the quantitative thermodynamic measure of this H+ gradient is

A

the proton electrochemical gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

the proton electrochemical gradient has 2 components

A
  1. concentration difference of H+ across the membrane (delta pH)
  2. difference in electrical potential between the 2 aqeuous phases separated by the membrane (delta trident)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

the electrochemical gradient is typically converted into units of and is referred to as (delta p)

A

electrical potential, mV

protonmotive force

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

use of protonmotive force is

A

essential for virtually every aspect of mitochondrial function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

electron transfer chain comprises a sequence of electron carriers with three separate regions where

A

redox energy can be conserved in the synthesis of ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

rate of respiration is controlled by

A

the demand for ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

coupling between respiration and ATP synthesis can be disrupted by

A

uncouplers - they abolish respiratory control and allow mitochondria to catalyze a rapid ATP hydrolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

oligomycin (an antibiotic) inhibits both the synthsis and

A

uncoupler-stimulated hydrolysis of ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

the energy from respiration can be coupled not only to the synthesis of ATP but also to

A

the accumulation of Calcium and the reduction of NAD to NADP

this can all be driven by the hydrolysis of ATP in anaerobic mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Four Basic Postulates of Mitchell’s Chemiosmotic Theory

A
  1. respiratory ETC should translocate protons
  2. the ATP synthase should function as a reversible proton-translocating ATPase
  3. energy-transducing membranes should have a low effective proton conductance
  4. energy-transducing membranes should posses specific exchange carriers to permit metabolites to permeate and osmotic stability to be maintained in the presence of high membrane potential
24
Q

Redox reactions are not restricted to the

A

ETC

25
Q

the tendency of the redox couple to donate electrons is quantified by

A

forming an electrical cell from 2 half-cells

26
Q

the KEY POINT for mid-point potentials is

A

redox couples with more negative Em7 values are more likely to donate electrons to redox couples with more positive Em7 values

27
Q

Mitochondrial Respiratory Chains: complex I

A

NADH-UQ oxidoreductase

28
Q

Mitochondrial Respiratory Chains: complex II

A

succinate dehydrogenase

29
Q

Mitochondrial Respiratory Chains: complex III

A

bc1 complex; UQ-cyt c oxidoreductase

30
Q

Mitochondrial Respiratory Chains: complex IV

A

cytochrome c oxidase

31
Q

Ion and metabolite transport in Mitochondria

A

mitochondria require a continual interchange of metabolites and end-products with the cellular cytosol
- at the same time the inner membrane must maintain a high protonmotive force for ATP synthesis

32
Q

Key Transport Processes: Monovalent cations

A

high negative membrane potential can lead to a 1000X accumulation of monovalent cations if transport occurred by a uniport mechanism - mitochondria possess a transporter that can exchange either Na or K FOR H

33
Q

Key Transport Processes: Calcium

A

there are 2 mitochondrial Ca transporters

  1. membrane potential-dependent uniporter
  2. Ca/2H or Ca/2Na antiporter
34
Q

perturbations in cellular Ca homeostasis may be important in many forms of chemically induced toxicity - the concentration of Ca is a critical factor in the regulation of

A

many metabolic prosses like regulation of activities of mitochondrial dehydrogenases

35
Q

six processes function in the regulation of intracellular Ca homeostasis

A
  1. electroneutral Na/Ca exchange
  2. Mg-dependent Ca-ATPase
  3. endoplasmic reticulum: uptake by Mg-dependent Ca-ATPase
  4. uptake-driven by transmembrane potential generated across inner membrane during coupled respiration
  5. efflux-electroneutral Ca/H exchange
  6. calcium-binding proteins (like calmodulin)
36
Q

Ca cycling is a major mechanism by which

A

toxins exert their deleterious effects in cells

37
Q

all mitochondria possess the

A

adenine nucleotide translocase, phophate carrier and pyruvate carrier

38
Q

key findings on metabolic conditions of H2O2 generation: 1. with malate + glutamate as respiratory substrates H2O2 production is

A

inhibited by rotenone

39
Q

key findings on metabolic conditions of H2O2 generation: 2. when succinate is used as respiratory substrate & electron flow is blocked by antimycin, mitochondria exhibit high rates

A

of H2O2 production

40
Q

key findings on metabolic conditions of H2O2 generation: 3. fatty acids and fatty acyl-CoA also support high rates of H2O2 production in the presence of

A

antimycin A

41
Q

mitochonrial generator of H2O2 is either a component of the respiratory chain or a chemical that is at equilibrium with is since

A

H2O2 production is maximal in HIGHLY REDUCED states

and is minimal in oxidized states like state 3

42
Q

functional consequences of mitochondrial oxidative stress

A

mitochondria contain 3 major types of redox active components:

  1. electron carriers of the respiratory chain
  2. protein sulfhydryl groups
  3. matrix GSH
43
Q

Toxicological relevance

A

mitochondria contain a large number of critical SH groups that must be in the reduced form for appropriate enzyme activity

44
Q

Mitochondrial Permeability transition: the transition is readily reversible and occurs when

A

Ca loading is followed or preceded by addition of a second agent

45
Q

Mitochondrial Permeability transition: perturbation of a phospholipid acylation-deacylation cycle is seen as a

A

central event leading to the transition

46
Q

Mitochondrial Permeability transition: calcium ions are hypothesized to increase activity of this cycle by

A

stimulating the mitochondrial phospholipase A2

47
Q

Mitochondrial Permeability transition: the inducing agent is thought to inhibit phospholipid re-acylation as result

A

phospholipase A2 reaction products accumulate and crease membrane permeability

48
Q

Mitochondrial Permeability transition: permeability transition can occur both with and without

A

matrix swelling

49
Q

inducing agents

A

sulfhydryl reagents, peroxides, intermediary metabolites, heavy metals

50
Q

protective agents include:

A

thiols & other reductants
phospholipase A2 inhibitors
calcium channel blocking agents
cyclosporin A

51
Q

Genome and Toxicity and Disease

A

carcinogens, mitochondrial DNA (mtDNA) is also a target

52
Q

several factors may contribute to selective adduct formation with mtDNA

A
  1. mtDNA lacks histone proteins which are associated with nDNA so mtDNA may be more accessible to electrophilic metabolites of xenobiotics
  2. the diverse and efficient DNA repair systems present in the nucleus are generally lacking in mitochondria
  3. enzymes that bioactivate xenobiotics to reactive electrophiles are present in the mitochondria
53
Q

mitochondrial DNA repair and cell injury: mutation rate of mtDNA in mammals is reported to be 5-10X that of

A

nDNA

54
Q

mitochondrial DNA repair and cell injury: mtDNA mutations may lead to decreased

A

respiratory capacity and an increase in release of ROI’s

55
Q

mitochondrial DNA repair and cell injury: the relatively small amounts of mtDNA as compared with nDNA make the

A

study of repair processes difficult

56
Q

mitochondrial genetics have several features that are unique and different from that of classical Mendelian genetics

A
  1. cytoplasmic location and high copy number
  2. mtDNA is maternally transmitted
  3. mixed intracellular populations of mutant and normal mtDNAs segregate during both meiotic and mitotic replication
  4. systemic OXPHOS defects show tissue-specific expression as a result of the different OXPHOS requirements of human tissues
  5. energetic capacities decline with age- probably because accumulation of mtDNA with age
  6. mtDNA has a high mutation rate partly due to lack of efficient repair systems

Toxicology (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions