L2 Detoxification & Neutrigenomics Flashcards

1
Q

1 - Genomics

2 - Allele

3 - Phenotype

A

1 = study of genes

2 = genetic variation eg eye colour

3 = genetic & environmental factors together

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2
Q

1- SNP

2 - Wild Type

3 - Heterozygous

A

1 - variation on DNA base, normal but influences how genes interact with environment

2 - Natural variant (stable)

3 - Gene variant inherited by one parent

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3
Q

COMMON SNPs:

1 - BCO1
2 - VDR
3 - FADS-1
4 - FADS-2
5 - TNF

A

1 - reduces beta-carotene conversion

2 - impacts Vit-D synthesis: A allele = <bone density & G allele = >osteoarthritis risk

3 - Fatty-acid 5 Desaturase = > O:6 to Inflammatory AA conversion (African Americans more common)

4 - Fatty-acid 6 Desaturase = < levels of anti-inflammatory EPA, DHA, ALA

5 - > inflammatory TBF cytokines

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4
Q

Processes that require METHYLATION

A

Gene regulation
DNA/RNA synthesis
Immune (tissue repair/inflammation/WBCs/illness)
Detoxification
Energy production
Myelination & NS

Methylation = a currency constantly being spent

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5
Q

METHYLATION consists of 2 cycles

A

Folate cycle

Methionine cycle

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6
Q

What is the Folate Cycle

A

Various enzymes (coded by MTHFR gene - can have SNP) convert Folate into its methylated (active) form 5-MTHF (Methylfolate)

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7
Q

Which Nutrients support Methylation

A

B6, B2, B3, Choline, Betaine, Zn, B12

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8
Q

What is Methylfolate (5-MTHF) need for in the body?

A

Building Neurotransmitters e.g; Serotonin, Dopamine, Noradrenaline

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9
Q

What is SAMe

A

The grandparent methyl-donor created from Methionine.

SAMe donates its methly group (processes below) & becomes Homocysteine which then needs to be converted back to Methionine (needs B12!)

Builds; hormones, neurotransmitters (GABA, Serotonin, Dopamine) - mood!, Joints, liver function, addictions/alcoholics

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10
Q

What is the Methionine Cycle

A

Also the SAMe cycle! Methionine creates SAMe (Grandparent Methyl donor!)

Methionine has Sulphur added to it creating SAMe

SAMe donates its methly group & becomes Homocysteine which then needs to be converted back to Methionine (needs B12!)

Homocysteine Doesn’t have Methyl group on its sulphur as it gave it to various processes. Enzyme Methionine Synthase (coded by MTR & MTRR genes) creates reactions to get it back.

Needs B12 and 5-MTHF (Methylfolate) a which donates its methyl group to make Homocysteine back to Methionine

Enzymes catalysing the process coded by genes:
MTR - SNP = < MS activity
MTRR - SNP = < B12 conversion to Methylated B12

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11
Q

What is Homocysteine?

A

Doesn’t have Methyl group on its sulphur. Enzyme reactions to get it back that needs B12 and 5-MTHF (Methylfolate) which donates its methyl group to make Homocysteine back to Methionine

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12
Q

Methylation disrupters

A
  • Age
  • Poor gut health (low HCI)
  • Low folate, B12
  • < co-factors
  • SNPs
  • Increased demand on processes (at expense of others
  • > toxins
  • Hormone imbalances eg oestrogen dominance
  • Drugs - OCP, HRT, metformin
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13
Q

What is the Transulphuration Cycle?

A

Another Homocysteine output route, converting it to Cystathione (via CBS gene) and onto:

  • Sulphate (detoxification of oestrogen) via Cysteine & SulphITE (wine, garlic)
  • Glutathione (antioxidant) via Cysteine
  • Urea via Amonia (protein)
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14
Q

How to support Transulphuration

A
  • Increase Zn, Choline & TMG (beets)
  • Reduce ammonia (<meat, >probiotics to reduce self synthesis
  • Reduce sulphur containing foods (wine, eggs, brassicas, garlic
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15
Q

What is COMT?

A

MTHFR (from folate cycle) gene that provides instructions for making a methyl dependent enzyme - catechol-O-methyltransferase.

20-30% Europeans have SNP which limits catechol removal

2 enzyme types,

1 creates in nerve cells & breaks down neurotransmitters

1 created in liver/kidneys/blood & converts some hormones inc oestrogen to its less active form

Common SNPs:

AA (worrier) = excess catecholamines, ie low COMT activity - not broken down = > oestrogen’s. higher dopamine levels; lower pain threshold, <stress tolerance, >oestrogen

GG (warrior) = fast catecholamine breakdown = lower dopamine levels, depression; higher pain threshold, > stress resiliency

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16
Q

Supporting COMT

A

Choline, B Vits, Folate, B12, support SAMe, avoid xeno-oestrogens

Reduce foods that >catechols (high protein)

Increase Mg

Reduce alcohol (triggers dopamine release)

Increase brassicas

Support phase II detoxification

17
Q

What is Urea Cycle & eNOS?

A

eNOS = Endothelium Derived Nitric Oxide Synthanase creates NO (vasodilator) from arginine

SNPs can <eNOS activity & NO + slow down ammonia detoxification = >toxic load, free radicals, BP & CVD risk

18
Q

Supporting eNOS

A

Eat rainbow (antioxidants)

Limit ammonia (animal protein)

> NO production with beet juice & L-arginine

19
Q

What is a toxin?

A

A poison produced in organisms that is active @ low levels

20
Q

What are Endogenous toxins?

A

INTERNAL

GI microbes
Dysbiotic bacteria, LPS
Metabolites
Poorly detoxed - recirculated hormones

21
Q

What are Exogenous toxins?

A

External, chemicals, eg:

BPAs/Plastics
Pesticides
Flame retardants
Farmed fish
Air pollution
Solvents
Smoked foods
Heavy metals - Aluminium, Mercury, Arsenic

22
Q

Antioxidant enzymes produced in humans & nutrients needed

A

Superoxidase Dismutase (Zn, Cu, Manganese)

Catalase (Fe)

Glutathione Peroxidase (Se)

Glutathione Reductase (B3)

23
Q

Antioxidants from plants

A

Vit E (sunflower seeds, almonds, olive oil, avocado, sweet potato, spinach)

Vit C (peppers, citrus peel, kiwi, berries, crucifer, mango

Flavonoids (quercetin, catechins, GLV

Carotenoids

24
Q

What are Metallothioneins & role in detoxification?

A

They are cysteine (legumes, eggs, chicken, sunflower seeds) rich proteins that bind to toxic heavy metals

Reduce OS

Help Zn & Copper homeostasis

25
Q

Detoxification phase Zero

A

Toxin entry into cell

Fat Sol via diffusion

Water Sol via transporter

26
Q

Detoxification- Phase 1

A
  • Makes fat sol toxins water sol for elimination
  • CYP450 enzymes create active binding site (they become more reactive)
  • SNPs can influence CYP450, faster or slower not good
27
Q

Common Phase 1 SNPs

A

CYP2E1 - alcohol

CYP1A2 - caffeine

CYP1A1 - oestrogen

28
Q

What’s Phase 2 detoxification

A

6 detox pathways add functional groups thru chemical reactions to deactivate toxins to make them safe for elimination

29
Q

Phase 2 - Step 1
GLUCURONIDATION

A

Requires; GLUCURONIC acid (apples, alfalfa, broccoli)

Enhanced by; citrus, brassica, turmeric

30
Q

Phase 2 - Step 2
SULPHATION

A

Key! Needs;

  • sulphur containing AA’s (cysteine & methionine)
  • Sulphur rich foods (eggs, onion, garlic, brassicas)

Molybdenum (legumes, GLV, whole grains)

31
Q

Phase 2 - Step 3
ACETYLATION

A

Inhibited by; Vits B & C deficiencies

Needs; B1, B5, C, butyric acid (SCFA)

32
Q

Phase 2 - Step 4
METHYLATION

A

Inhibited by; < Folate or B12

Needs; Methionine, Betaine, Choline, B2, B6, B12, Folate, Mg

33
Q

Phase 2 - Step 5
AMINO ACID CONJUGATION

A

Inhibited by low protein diet

Needs; GLYCINE (legumes, seaweed, cauliflower, bone broth, meat, fish, eggs

34
Q

Phase 2 - Step 6
GLUTATHIONE CONJUGATION

A

Inhibited by; deficient Se, B6, Zn, Glutathione

Enhanced by; Brassicas, turmeric, citrus peel, alpha-lipoic acid

Self synthesised by cysteine

35
Q

What is Glutathione, where does it come from & what is it for?

A

A crucial antioxidant

From legumes, sunflower seeds, eggs, chicken

Protects mitochondria
Binds & transports mercury out of cells & x-bbb

Low levels assoc; neuro-degenerative, autoimmune, CVD, liver disease, COPD

SNP common

36
Q

How to support Glutathione?

A

< OS
< toxic load
> alpha-lipoid acid (grandfather antioxidant, recycles oxidised glutathione)
Milk thistle
NAC
Reservatrol
Brassicas
Cordyceps