Basic Mechanisms of Toxicants II (4)

Question 1

Regarding chemicals that specifically interact with protein targets, chemicals can also [promote/inhibit] cellular respiration. How?

Answer 1

inhibit

inhibit proteins or enzymes involved in oxygen consumption, fuel utilization, and ATP production that will cause energy depletion and cell death

Question 2

List two things that can disrupt something in cellular respiration

Answer 2

• cyanide
• carbon monoxide

Question 3

What does cyanide do?

Answer 3

inhibits mitochondrial cytochrome c oxidase to prevent cellular respiration

inhibits electron transfer

Question 4

What does carbon monoxide affect?

Answer 4

displaces oxygen from hemoglobin causing hypoxia

Question 5

How can some chemicals affect nucleotides, lipids, and amino acids?

Answer 5

inhibit their production

Question 6

How does amanitins from death cap mushrooms cause issues?

Answer 6

RNAse molecule —> breakdown mRNA —> can’t make proteins

Question 7

Organs particularly to toxin damage are the _____ and _____

Answer 7

liver
kidney

Question 8

What happens with toxins and hepatic inflammation?

Answer 8

halothane can covalently bind to liver proteins to trigger an autoimmune reaction

Question 9

What are main categories of liver toxicity?

Answer 9

1. hepatic necrosis
2. hepatic inflammation
3. chronic liver damage

Question 10

What can be components of nephrotoxicity?

Answer 10

1. changes in glomerular filtration rate
2. allergic nephritis
3. chronic nephritis

Question 11

How do NSAIDs affect the kidney via GFR?

Answer 11

reduce prostaglandins which in turn reduces blood flow/GFR

Question 12

What are molecular mechanisms of cellular dysfunction?

Answer 12

1. chemicals that cause DNA adducts
2. chemicals that cause protein adducts
3. chemicals that cause oxidative stress
4. all can cause inflammation which can lead to cellular dysfunction

Question 12

Review apoptosis

Answer 12

controlled

Question 13

Review necrosis

Answer 13

causes inflammation, uncontrolled

Question 14

Regarding necrosis, agents that disrupt functions, especially ____ and ____ will cause death

Answer 14

energy-producing function of the mitochondria

protein synthesis

Question 15

What are the 3 primary metabolic disorders jeopardizing cell survival? (necrosis)

Answer 15

1. ATP depletion
2. sustained rise in intracellular Ca2+
3. overproduction of ROS, RNS

Question 16

What does ATP have a role in?

Answer 16

cellular maintenance both as a chemical for biosynthesis and as a major source of energy

Question 17

Look at reasons how ATP plays a role in cellular maintenance

Answer 17

Question 18

What happens with ATP depletion regarding pumps?

Answer 18

compromised ion pumps: increases extracellular Na+ and Ca2+, and water follows

loss of ionic and volume regulatory controls

cell swelling and lysis —> necrosis

Question 19

What kind of things inhibits electron transport which in turn impairs ATP synthesis?

Answer 19

1. cyanide
2. rotenone
3. paraquat

Question 20

What are the types of agents (categories) that impair ATP synthesis?

Answer 20

1. inhibitors of electron transport
2. inhibitors of oxygen delivery (carbon monoxide, etc)
3. inhibitors of ADP phosphorylation
4. chemicals causing mitochondrial damage (antivirals)

Question 21

What types of things is Ca2+ involved in?

Answer 21

Question 22

What ion’s intracellular levels are very regulated?

Answer 22

calcium

Question 23

What are the 4 mechanisms of Ca2+ regulation?

Answer 23

1. extracellular Ca2+ ATPase
2. endoplasmic reticulum Ca2+ ATPase
3. extracellular Na+/Ca2+ exchanger
4. mitochondrial Ca2+ uniporter

Question 24

What is a consequence of increased intracellular Ca2+?

Answer 24

excitotoxicity

Question 25

What are the consequences of the rise of intracellular Ca2+?

Answer 25

1. depletion of energy reserves
2. dysfunction of microfilaments
3. activation of hydrolytic enzymes
4. generation of ROS/RNS

Question 26

Look at summary slide for this lecture

Answer 26