What Is Detoxification
What Is Detoxification
What Is Detoxification
PHASES OF DETOXIFICATION:
1. PHASE 1 REACTION:
a. ENZYME TRANSFORMATION:
- Either aromatic or aliphatic
- Performed by a family of enzymes called the cytochrome
P450s
- (CYPs)
- CYPs are able to recognize and modify countless different
toxins
- versatile
- However, they metabolize toxin very slowly
- CYP3A4 (1-20 molecules/sec) vs. SOD (million molecules/sec)
- Overcome by producing large amount of CYPs (5% of total
liver
proteins and intestines)
- Prominent role in the metabolism of prescription drugs (50%)
- Other enzymes in Phase 1: Flavin monooxygenase (FMOs),
alcohol
and aldehyde dehydrogenases, monoamine oxidases
2. PHASE 2 REACTION:
a. ENZYMATIC CONJUGATION:
- Why need phase II?
i. Phase I reactions are not sufficient to make the toxin water
soluble
enough to complete the entire excretion pathway
ii. Product from the phase I reactions have been rendered more
reactive than the original toxins
- Phase II
modify phase I products to both increase the
solubility
and reduce their toxicity
- Prominent role in the protection against chemical
carcinogenesis
especially at the initiation phase of cancers
of
antioxidant response
b. The role of NrF2:
- Nrf2 in cytoplasm, inactive oxidative stress activated
travel to nucleus turn on the genes of many antioxidant
proteins (glutathione & SOD)
- Important role in initiating heavy metal detoxification and the
recycling of CoQ10, a potent antioxidant
3. PHASE 3 REACTION:
a. Transport:
- Phase III transporters present in many tissues i.e. liver,
intestine, kidney and brain
- Provide a barrier against xenobiotic entry
- Necessary to excrete the newly formed phase 2 products out
of the cell
- Belong to a family of proteins called ABC Transporter (ATP
Binding
cassette)
- Require chemical energy (ATP) to actively pump toxins
through the cell membrane and out of the cell
- In liver: these transporters move glutathione, sulfate and
glucuronide conjugates out of cell into the bile for elimination
ENZYMES OF DETOXIFICATION:
PHASE 1 / 2 IMBALANCE:
OVERDOSE OF ANALGESIC ACETAMINOPHEN /
PARACETAMOL:
-
DETOXIFICATION SUPPORTS:
Bile secretion:
-
Antioxidation:
-
IMPAIRED DETOXIFICATION:
-
fatigue
headaches
chronic joint or muscle pain
digestion issues including gas, heartburn, bloating, diarrhea or
constipation, and abdominal pain
insomnia
autoimmune diseases
hormonal imbalances like PMS or menopausal symptoms
acne or skin rashes
anxiety or depression
allergies
inflammation
chemical sensitivities