Session 7 - Liver Detoxification

Question 1

What are the functions of the liver?

Answer 1

• bile production
• filtration & storage of blood
• 500 vital functions
• stores iron & vitamin a
• processes toxins like acetaldehyde in alcohol metabolism
• metabolism & detoxification
• regeneration

Question 2

What are the role of kupffer cells?

Answer 2

Serve as a first line defense against immunoreactive material passing from GIT via portal circulation.

They are the resident macrophages in liver and account for 80-90 of total number of natural macrophages. They release cytokines, chemokines etc
Can regenerate.

Question 3

What is the purpose of bile?

Answer 3

• carrier of toxic substances
• removes products of detoxification from liver
• emulsifies dietary fats for digestion

Question 4

What does the detoxification and biotransformation of exogenous substances involves?

Answer 4

• hepatic filtering and phagocytosis
• intestinal microbiota and gut-associated lymphoid tissue (GALT)
• phase 1 liver detoxification pathway
• phase 2 liver detoxification pathway

Question 5

What are the purpose of the two detoxification pathways (3rd role)

Answer 5

to render endogenous and xenobiotic substances more water soluble and easier to excrete. Allows neutralization of unwanted chemical compounds (pesticides, drugs, medicines)

Question 6

What happens in phase 1 pathway?

Answer 6

Small chemical changes making compounds more hydrophilic for elimination by kidneys or further acted upon by phase 2.

Question 7

What is the important enzyme in pathway 1?

Answer 7

Heme Dependent enzymes (phase 1 reactions):

Cytochrome p450 (cyt) makes toxic compounds (fatty acids, steroids, xenobiotics) water soluble so they can be excreted.

Question 8

What is a cofactor for Cytochrome P450?

Answer 8

Iron & NADH

Question 9

What neutralises free radicals produced by phase 1 liver metabolism of chemical toxins?

Answer 9

Glutathione

Question 10

What is glutathione (reduced from GSH) made up from and what is its function?

Answer 10

Amino acids: glutamine, glycine, and cysteine.
Acts as an antioxidant in phase 1
Conjugates heavy metals in phase 2

Question 11

What nutrient replenishes glutathione?

Answer 11

Vitamin C

Question 12

What are the cofactors for enzyme glutathione reductase?

Answer 12

Riboflavin/B2,
niacin/B3
vitamin c

Question 12

What are the cofactors for Phase 1 detoxification?

Answer 12

Vitamin C, copper, magnesium, zinc, thiamin, riboflavin, niacin, b6, folate, b12, iron, branch chain amino acids.

Question 13

What can an underactive Liver 1 pathway manifest an intolerance to?

Answer 13

Intolerance to perfume, caffeine, sugar cravings, bloating, constipation, abnormal fat metabolism. Environmental chemicals. An overactive Phase 1 can result in excess free radical production.

Question 14

What are inducers of phase 1?

Answer 14

Drugs, environmental pollutants, pesticides, high protein diets, saturated fats, indoles from cruciferous vegetables

Question 15

What are inhibitors?

Answer 15

phytochemicals in foods: grapefruit juice, curcumin from turmeric.

Question 16

What foods assist in functioning of Liver Detox Phase 1?

Answer 16

Cuciferous vegetables, green tea, selenium, methionine.

Question 17

What does Liver detoxification Phase 2 involve?

Answer 17

The conjugation (change) of intermediate metabolites made in phase 1 with glucuronide, sulphate, or glutathione.

The biotransformed water soluble toxicants are excreted via the bile and faeces or kidneys & urine.

Question 18

What are the required nutrients for phase 2?

Answer 18

Amino acids, vitamins, minerals.

Question 19

What are the inducers and inhibitors of phase 2?

Answer 19

Inducers: cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods

Inhibitors: Low protein diet, Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), Aspirin, probenecid (gout medication).

Question 20

What are the 3 main enzyme systems which metabolises alcohol?

Answer 20

• Alcohol and acetaldehyde dehydrogenases
• Microsomal ethanol oxidising system (MEOS) using cytochrome P450 enzymes.
  Catalase

Question 21

What cofactor is required for these enzyme systems?

Answer 21

Iron

Question 22

What nutrients are alcoholics deficient in?

Answer 22

Iron, zinc, vitamin a, b vitamins.

Question 23

What are the effects of alcohol on liver enzymes?

Answer 23

ALT - released when liver is damaged
ALP- an enzyme elevated during liver injury.
GGT - marker of liver injury (most sensitive biomarker of alcohol consumption)

Question 24

What nutrients can support alcohol detoxification?

Answer 24

Vitamin B3 (metabolise alcohol) Glutamine (precursor to GABA - decreases cravings and relieves alcohol detoxification) Phenylalanine

Question 25

List other nutrients to support alcohol detoxification.

Answer 25

``` Cruciferous vegetables Glutathione Vitamin B Complex Selenium Iron (cofactor for C450) Zinc (cofactors for DNA damage repair enzyme) Nuts Vitamin A Proteins Carnitive Antioxidants A, C ```

Question 26

What are the signs and symptoms of phase 1 liver pathway induction?

Answer 26

Bloating, tiredness, sweating at night, itchy skin, headaches, allergies, poor sleep, gut problems. Toxic metabolites travel in the blood rather than being excreted.

Question 27

What will be the nutritional impact of dysfunctional phase 1 in the body?

Answer 27

- overburdening of phase 2 - activation of kupffer cells leading to excess release of cytokines - depletion of nutrients (gutathione, niacin)

Question 28

What could be one of the biochemical reasoning pathways for bloating?

Answer 28

Toxic TMAO travel to gut (gut-liver axis) and harms microbiome and gut epithelium causing bloating.

Question 29

Which over the counter meds are detoxified via phase 1?

Answer 29

Salicylates and ibuprofen

Question 30

What are the largest macrophages with phagocytotic activity for the protection of liver cells called?

Answer 30

Kupffer cells

Question 31

Which group of enzymes are imperative for liver detox 1?

Answer 31

Cytochrome 450 (group of haem dependent enzyme)

Question 32

True or false? Curcumin and grapefruit cause an upregulation of phase 1 liver detoxification.

Answer 32

False they cause a lowering of phase 1

Question 33

True or false - Glutathione is required as a cofactor for detoxification pathway to support cytochromes.

Answer 33

False – it is required as an antioxidant in phase 1 and as a conjugant in phase 2.

Question 34

What is the form of glutathione that acts as an antioxidant?

Answer 34

Reduced Glutathione GSH | GSH is depleted by the oxidative by-products of phase 1, the GSH-dependent phase 2 activity is inhibited.

Question 35

T/F - Vitamin C is required as a cofactor for glutathione peroxidase enzyme

Answer 35

False | Selenium is required as cofactor for glutathione peroxidase enzyme (it’s a selenoprotein)

Question 36

Which primary nutrients ensure the optimal functioning of phase 1 liver detoxification?

Answer 36

``` Vitamin C Magnesium Zinc Copper Which all help with optimal functioning ```

Question 37

Which nutrients are required as cofactors for excretion of thyroxine, catecholamines and oestrogen via sulphation pathways?

Answer 37

Sulphation pathways require pyridoxine, methionine, cysteine, glutathione, taurine and molybdenum as cofactors.

Question 38

Which of the following induce the phase 2 liver detoxification pathway?

Answer 38

Cigarette smoke, birth control pills and limonene | NSAIDS, low protein diet and tartrazine inhibit this pathway

Question 39

T/F - Acetyldehyde dehydrogenase, MEOS and catalase are the enzymes involved in alcohol metabolism

Answer 39

True - The enzymes alcohol dehydrogenase (ADH), cytochrome (CYP2E1), and catalase all contribute to oxidative metabolism of alcohol. ADH, (in cytosol), converts alcohol (i.e., ethanol) to acetaldehyde (using NAD+). Catalase, (in peroxisomes), uses H2O2 to oxidize alcohol. At excessive levels of alcohol, CYP2E1, in the cell’s microsomes (MEOS), becomes active. Acetaldehyde is metabolized finally by aldehyde dehydrogenase (in mitochondria) to form acetate.