Lecture 7 Flashcards
Name the 8 toxicity mechanism.
- Lipid peroxidation (when we have radicals, ROS)
- Acidosis
- Energy production in cells
- Nerve toxic compounds
- Allergy causing compounds
- Teratogenic compunds
- Genotoxic compounds
- Carcinogens
What is the normal pH value in our blood?
7.35-7.40
What is it called over 7.40?
What is it called under 7.35?
When does acute effect occur?
What kind of chronic effect occur?
Over 7.40: alkalosis
Under 7.35: acidosis
Acute effect: death when pH<7 or pH>8.
Chronic effect: calcium loss, kidney diseases etc.
How are minor pH-variations handled?
- Buffers in blood (HCO3-, HPO42-, H+) - regultate if there is a small change in pH
- Increased CO2 exhalation (CO2: acid gas —> increase breathing: increased pH in our body)
- Increased acid excretion via urine
Are acids strongly or poorly absorbed in the stomach?
Poorly, especially strong acids because they are ionic.
What are masked acids?
Masked acids can be metabolized and cause acidosis.
Draw the reaction of an ester and two other molecules from p. 6, where they are turned into acids/alcohols.
What is the metabolism of alcohols? Draw the reaction of methanol to formic acid.
P. 7
What is the difference between primates and non-primates when it comes to the metabolism of formic acid?
Non-primates can metabolise formic acid to CO2 and water, while primates (like humans) can’t. The formic acid gets accumulated in us.
Hydrophilic or electrophilic:
Methanol?
Formaldehye?
Methanol: hydrophilic
Formaldehyde: electrophilic
Why do you want to inhibit the alchol dehydrogenase from catalyzing methanol to formaldehyde?
Because formaldehyde is electrophilic which means it can react with nucleuophiles —> dangerous for us!
The metabolism is slow so if you can inhibit the alcohol dehydrogenase it will have time to go out.
Draw the metabolism of ethanol, where it become acetic acid.
P. 9.
If a person with a deficiency of acetaldehyde dehydrogenase drink alcohol (ethanol), what happens?
The metabolism can’t go further than acetaldehyde which means there will be an accumulation. Aldehyde is a litte electrophilic which could be bad for us.
Can humans convert acetid acid? If yes, into what?
Yes. Into water and CO2, which means we can tolerate more of acetic acid than formic acid. But if there’s too much acetic acid it can cause acidosis.
Which molecule can help with the metabolism of alcohol?
Fructose. If a lot of fruit when you’re deunk and it will help you get woken up!
Describe the energy production in cells. What do you call molecules that interfere with this process?
- Nutrient’s chemical bond energy —> 2. Co-factors with high reduction potential (NADH) —> 3. High phosphorylation potential by ATP.
You call the molecules toxic!
What is the purpose of the citric acid cycle? How is the citric acid cycle connected to oxidative phosphorylation and oxygen transport?
It uses oxygen and energy is created in the form of the molecules: NADH, FADH2 and GTP. The citric acid cycle is a series of chemical reactions that removes high-energy electrons and uses them in the electon transport chain to produce ATP.
Electron transport chain uses the energy molecules NADH and FADH2 to create a high concentration of H+ (electrochemical gradient) on one side of the cell membrane, which will be power a pump to produce ATP.
The oxygen in the blood takes care of the electron and water is created.
What kind of iron is bound ti hemoglobin?
Fe(II).
What happen if there if 50 % of O2 and CO in the blood?
CO will bind to 99.5 % of the hemoglobin while O2 will bind to < 0.5 %.
CO binds to Fe(II) much stronger than oxygen, sp hemoglobin could loose the ability to transport oxygen if there is too much CO.
What happen if hemoglobin — Fe(II) and H2O2 are together?
H2O2 is an oxident, so it can oxidize Fe(II) inti Fe(III) —> hemoglobin will convert to methaemoglobinemia, and it can not longer transport oxygen. Radicals are also formed, which can cause damage to red blood cells.
What molecule need to be involved so that hemoglobin — Fe(II) and H2O2 are together?
Aromatic amines (benzene + NH2 in this case)
What compunds resembles acetic acid and can block the enzyme converting citric acid into cis-actonic?
Fluoroacetic acid.
What enzyme complex can be disturbed in the citric acid cycle in this course? How can the enzyme be inhibited?
Enzyme complex IV. The Fe(III) on the heme-group on the enzyme complex can be the target of HCN, H2S. When these molecules bind to the irons on the heme group is blocks the respiration chain, very dangerous!
How is HCN formed? Draw the reaction using NaCN + H3O+.
NaCN + H3O+ —> Na+ + H2O + HCN
