Detox & Biotrans

Question 1

Detoxification

Answer 1

to remove the toxic quality of a substance

Question 2

Biotransformation

Answer 2

the chemical modification made by an organism on a chemical compound

Question 3

Xenobiotics

Answer 3

compounds foreign to the body (exogenous), which include: food additives, pesticides, solvents, plastics, industrial products

Question 4

Within ____ to ____ seconds after first smelling a solvent, you go “nose blind”

Answer 4

30-60 seconds

Question 5

How are xenobiotics absorbed?

Answer 5

• Simple diffusion
• Pores/skin
• Specialized transport (lead via Ca & Fe absorption, cadmium via Fe absorption)
• GI tract
• Lungs

Question 6

Where are xenobiotics stored in the body?

Answer 6

• plasma protein bound (longer 1/2 life)
• adipose tissue
• bone accumulation

Question 7

Do all xenobiotics effectively go through biotransformation?

Answer 7

No

Question 8

Phase 1 is also known as

Answer 8

Functionalization

Question 9

What happens during functionalization?

Answer 9

Responsible for the 1/2 life of a compound in the blood. Endogenous compounds are produced, and compounds are converted into metabolites (either more or less toxic than parent compound) to make them ready for Phase 2

Question 10

Phase 2 is also known as

Answer 10

Conjugation

Question 11

What happens during conjugation?

Answer 11

Metabolites from Phase 1 combine with endogenous molecules and usually become less toxic and more water soluble

Question 12

Phase 3 is responsible for what?

Answer 12

• excretion of xenobiotics

- prevention of recycling

Question 13

Phase 1’s 3 main mechanisms are

Answer 13

1. Hydrolysis
2. Reduction (PON1)
3. Oxidation (CYP450)

Question 14

At what pH are xenobiotics recycled by the kidney back into circulation?

Answer 14

urine pH <7.4

Question 15

Urine has to be at least what pH to excrete xenobiotics?

Answer 15

> 7.5

Question 16

What 3 molecules are required for Phase 1?

Answer 16

1. CYP450 (requires heme)
2. NADPH or NADH CYP450 reductase
3. Cytochrome b5 reductase

Question 17

Under conditions of starvation or fasting, which one of the 3 required Phase 1 molecules is less available?

Answer 17

NADPH

Question 18

What are the 2 other requirements for Phase 1?

Answer 18

1. oxygen

2. intact phospholipid matrix (messed up by trans fats)

Question 19

How many CYP450 families are found in humans?

Answer 19

18 families

Question 20

Where are most CYP450 enzymes found in the body?

Answer 20

Endoplasmic reticulum of the

• liver
• kidney
• sm intestine
• lung
• adrenal glands

Question 21

Which 2 tissues are CYP450 enzymes NOT found?

Answer 21

1. striated muscle

2. RBCs

Question 22

Majority (80%) of the CYP enzymes in the intestines are family….

Answer 22

3A4

Question 23

Which CYP families have multiple enzymes and are inducible?

Answer 23

1, 2, 3, 4

Question 24

What are the 4 main synthetic reactions (daily functions) of CYP?

Answer 24

1. cholesterol –> bile acids, steroids
2. Vit D hydroxylation
3. Alkanes–> fatty acids
4. Fatty acids –> eicosanoids (prostaglandins, leukotrienes, thromboxanes)

Question 25

Induction of CYP enzymes requires ________ exposure

Answer 25

Regularly repeated exposure

Question 26

Inhibition of CYP enzymes requires _______ exposure

Answer 26

A single exposure

Question 27

Lipopolysaccharides (LPS) ________ [suppress/stimulate] all CYP function

Answer 27

Suppress function

Question 28

Nutrients needed for Phase 1

Answer 28

- Iron - Copper - Vit A - Vit B2 - Vit B1 - Selenium

Question 29

Organophosphates are not toxic to humans until...

Answer 29

metabolized by CYP 3A4 enzymes

Question 30

By-products of all Phase 1 activity will always result in ______ pro-oxidants

Answer 30

Elevated/increased

Question 31

Tests for CYP function include (3)

Answer 31

1. erythromycin breath test 2. antipyrene clearance test 3. caffeine clearance test

Question 32

Important points to remember about Phase 1

Answer 32

1. All about the 1/2 life 2. hormone metabolism and production of anti-inflammatory molecules 3. all Phase 1 produces free radicals 4. Microbiome impacts CYP function greatly 5. Inflammation impacts CYP function greatly

Question 33

Where is PON1 produced in the body?

Answer 33

Liver, carried on HDL through circulatory system

Question 34

PON1 levels and activity are directly related to prevention of what condition?

Answer 34

cardiovascular disease

Question 35

Caucasions have PON1 SNP in ____% of the population

Answer 35

75%

Question 36

Reduced PON1 is related to which conditions?

Answer 36

- heart disease - diabetes (1&2) - viral hepatitis & cirrhosis

Question 37

Main activities of PON1

Answer 37

1. antioxidant 2. anti-inflammatory 3. anti-fibrinolytic

Question 38

PON1 activity is reduced by

Answer 38

rancid oils/oxidized lipids

Question 39

PON1 activity is inversely associated with

Answer 39

- BMI - % body fat - C-reactive protein

Question 40

What can increase PON1 activity?

Answer 40

- exercise (aerobic & anaerobic) - Mediterranean diet - quercetin - green tea - blueberries - pomegranate juice - Hallawi dates - Vit C & E - black elderberry - EVOO - walnuts - aspirin - coconut oil

Question 41

PON1 summary

Answer 41

- made in the liver, delivered through the body on HDL - antioxidant activity - anti-inflammatory - cardio protection - blood sugar regulation - neuroprotection - mood balancer - polymorphic - caucasians more likely to have deficiency (snps) - ox. stress and inflammation can reduce activity - mercury can reduce activity