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Karl Goldkamp   ND,  L.Ac., Dipl. Oriental Medicine The Center For Natural Medicine Family Practice 81 Halls Road, Old Lyme CT.  The Methylation cycle  and  its common polymorphisms
What is Methylation ,[object Object]
Why is Methylation important ,[object Object],[object Object]
Why is methylation important con’t ,[object Object],[object Object],[object Object]
Why is methylation important con’t ,[object Object],[object Object]
Why is methylation important con’t ,[object Object],[object Object],[object Object],[object Object],Deth, Richard. Molecular Aspects of Thmerosal-induced Autism
Homocysteine & Methylation ,[object Object],[object Object],[object Object]
Homocysteine Theory  of Arteriosclerosis ,[object Object],[object Object],McCully, Kilmer. Homocysteine, vitamins, and vascular disease prevention, 2007
The Homocysteine story ,[object Object],[object Object],The Fall and Rise Of Kilmer McCully New York times Magazine, 8-7-1997
The Homocysteine story ,[object Object],The Fall and Rise Of Kilmer McCully New York times Magazine, 8-7-1997
The road to discovery ,[object Object],McCully, Kilmer. Homocysteine, vitamins, and vascular disease prevention, 2007
The road to discovery ,[object Object],[object Object],[object Object],[object Object]
The Road to Discovery ,[object Object],[object Object]
Kilmer McCully get his due 1997 2000
The road to discovery ,[object Object],[object Object],[object Object],[object Object]
Other cases  ,[object Object],[object Object],Stare FJ. Experimental atherosclerosis in cebus monkeys. J Exp Med 1953; 98:195-218
Other cases con’t ,[object Object],[object Object],[object Object],Carson, NAJ. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland.  Arch Dis Child 1962
Other cases con’t ,[object Object],[object Object],[object Object],[object Object],[object Object],McCully, Kilmer. Homocysteine, vitamins, and vascular disease prevention, 2007
Other cases con’t ,[object Object],[object Object]
Putting the associations together   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
This diagram represents both the folate cycle and the methylation cycle (aka the SAM or Methionine cycle).
Steps in the Methylation cycle ,[object Object],[object Object],[object Object],[object Object]
Steps in the methylation cycle ,[object Object],[object Object],[object Object],[object Object],[object Object]
Steps in the Methylation cycle ,[object Object],[object Object],[object Object]
Steps in the Methylation cycle ,[object Object],[object Object],[object Object],[object Object]
Steps in the Methylation cycle ,[object Object],[object Object],[object Object],[object Object]
The Methylation Cycle MTHFR Glutathione CBS MS MSR
The Betainehomocysteine-Methyltransferase (BHMT)  conversion of Homocysteine
A Function of Folate ,[object Object],[object Object],[object Object]
Dietary Folate & the Folate cycle ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Dietary Folate & the Folate cycle ,[object Object],[object Object],[object Object],[object Object],[object Object]
The Methylation Cycle MTHFR Glutathione CBS MS MSR
The Methylation cycle and the Folate cycle glutathione
Another way to view it MS / MSR MTHFR CBS Glutathione 5,10 methyleneTHF
Think of this as a coupling of different cycles Redox Rep 2003, 8(1): 57-63
Methylation  ->  Trans-sulfuration  –>  glutathionine synthesis Under conditions where homocysteine conversion to methionine is dominant then folate and B12 are critical micronutrients.
During oxidative stress With oxydative stress the conversion of homocysteine to cysteine and  glutathione,is the dominant flow and B6 is the critical micronutrient. While the transmethylation of homocysteine to methionine is inhibited.
Homocysteine regulation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Think of this as a coupling of different cycles Redox Rep 2003, 8(1): 57-63
Homocysteine regulation con’t ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
MTHFR ( methylenetratrahydrofolate reductase ) The  MTHFR  enzyme is an essential enzyme in the folate cycle.  It catalyzes   5,10-methylenetetrahydrofolate      5-methyltetrahydrofolate .  The later serves as a methyl donor for the remethylation of homocysteine to methionine through B12 to methyl-B12.  MTHFR  is the most common SNP in the pathway .
MTHFR con’t ,[object Object],[object Object],[object Object],[object Object]
The Methylation cycle and the Folate cycle glutathione Sulfate
The polmorphisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Single nuclear polymorphism
SNPs of MTHFR ,[object Object],[object Object],[object Object]
MTHFR C677T Polymorphism  and its role in disease ,[object Object],[object Object],[object Object],[object Object],Schwahn B, Rozen R (2002). "Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences.".  American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
MTHFR C677T Polymorphism  and its role in disease ,[object Object],[object Object],Schwahn B, Rozen R (2002). "Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences.".  American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
C677T MTHFR & Depression ,[object Object],[object Object],Coppen, A.  J Psychopharmacol. 2005 Jan;19(1):59-65.   Treatment of depression: time to consider folic acid and vitamin B12.
MTHFR & depression ,[object Object],[object Object],[object Object]
Neural Tube Defect ,[object Object],[object Object],[object Object],[object Object],Folates and the fetus,  European Journal of Obstetrics & Gynecology and Reproductive Biology ,  Volume 71, Issue 2 ,  February 1997 ,  Pages 105-111
Where can we supplement
Testing 5 year old ASD (Austistic spectrum disorder) child Metametrix labs  www.metametrix.com
Oxidative Stress Indicators ,[object Object],[object Object]
Intracellular testing  of antioxidant function ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],http://www.spectracell.com
Female 60 years old, Hx stroke,  meds lipitor with CoQ10, fish oil, vitamin D
 
 
Female 60 years old, hx stroke,  meds lipitor with CoQ10, fish oil, vitamin D
 
Female 56, Hx ulcerative colitis,  meds: sulfalazine, lipitor, Supplements: folate, fish oil, antioxidant drink, coQ10
 
 
See any patterns?
 
Female 68, recent dx of sarcoidosis
 
 
 
See any Patterns ?
 

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METHYLATION CYCLE AND IT\'S POLYMORPHISM