Glycine - GCAT / SHMT (Head Injuries, Glutathione, VOC Detoxification)

Although little known, GCAT is the gene that processes the Essential Amino Acid L-Threonine into Glycine using the cofactor B6 (P5P form). Interestingly, the SHMT gene (SHMT1 in eukaryotes cystolic, while SHMT2 being in the mitochondria) uses L-Serine and converts it into Glycine using B6 as well. Glycine can be found in connective tissue (e.g. ligaments of chicken and beef, Collagen Protein Powder, Bone Broth). Why do some people really benefit from some of these foods ? Hmmmm. For folks with significant histamine issues - they have long ago learned to stay away from Bone Broth.

Glutathione is made up of Glycine , Glutamine, and Cysteine. Glutamine is very prevalent in many foods, primarily animal protein. Cysteine as well. However, Glycine is not as prevalent - and the body often relies on the GCAT and SHMT genes to create Glycine. Glycine helps lower glutamate in the brain by drawing it down a pathway in the formation of Glutathione when combined with NAC (Cystein). Some people suffer from elevated levels of glutamate in the brain that cause neuro excitatory issues and inflammation - Glycine - can lower glutamate levels in the brain.

I have begun to see a pattern related to Glycine levels, Glutathione levels, and folks who have Traumatic Brain Injuries and neuro excitatory issues (difficulty sleeping, overstimulation) - they are severely mutated on GCAT and or the SHMT genes! It gets worse when mutations in the glutamate clearing genes (GOT, GAD, etc) are also compromised. Those who have tried Glycine supplementation have reported significant benefit. Sometimes NAC (Cysteine) is beneficial too, but only when iron is known not to be high. When iron is high, excess unbound iron can combine with cysteine and form the damaging hydroxyl free radical.

Glycine also has research that indicates it can help lower some nasty strains of Clostridia bacteria in the gut.

For people who have neuro excitatory issues (too much glutamate), and also have significant mutations on the NMDA receptors in the brain (GRIN genes) this is a triple whammy. Martin Pall's research from over a decade ago highlighted this (originally focused on Chronic Fatigue Syndrome), and when combined with excess nitric oxide from NOS2 (iNOS) combined to form peroxy nitrite - another damaging free radical. The TRP receptors are also connected in this process. Martin's Research would eventually shift away from just chronic fatigue syndrome to be focused on EMF exposure, which he found to stimulate the production of excess nitric oxide in some, who have mutations on the CACNA1C gene.

Glycine is also the key amino acid in the phase 2 detoxification and conjugation process of the Volatile Organic Compounds (VOC's) benzene, ethyl benzene, styrene, and xylene(s) [3,4]. VOC's are incredibly common in certain areas and can end up in the basements of houses (via a process known as vapor intrusion according to EPA documents, and an interview with the EPA in July of 2018)[1,2]. If adequate ventilation doesn't evacuate them they generally 'sink' to the basement and floor (they are heavier than the normal composition of 'air'). A radon mitigation system can help provide adequate ventilation, otherwise, a charcoal based filtration system, or a charcoal impregnated furnace filter can help remove the VOC's. VOC's are also commonly released from mattresses, furniture, gasoline, plastics, pretoleum products, etc.

You may imagine that somebody who has VOC toxicity / exposure, a head injury, and compromised GCAT / SHMT genes - this may create some substantial hurdles to healing. Glycine is found in connective tissue, and believe it or not, ice cream - if your child feels better after eating glycine, this could be one reason!

[1] EPA Interview, July 2019, Mike Kreder

[2] https://www.epa.gov/vaporintrusion/technical-guide-assessing-and-mitigating-vapor-intrusion-pathway-subsurface-vapor

[3] Detoxification of Benzoic Acid in Workers Exposed to Toluene Using Food Rich in Glycine Abdul Rohim Tualeka1, Michael Agung Irianto1 Adli Prasetyo1, Ike Agustin Rachmawati1, Erwin Dyah Nawawinetu2 1Department of Occupational Health and Safety, Faculty of Public Health, Airlangga University, Indonesia, 2Diploma Study Program of Industrial Hygiene and Occupational Health, Universitas Airlangga, Indonesia

[4] Contribution towards a Metabolite Profile of the Detoxification of Benzoic Acid through Glycine Conjugation: An Intervention Study Cindy Irwin,#1 Mari van Reenen,#1,2 Shayne Mason,1 Lodewyk J. Mienie,1 Johan A. Westerhuis,2,3 and Carolus J. Reinecke1,*Viswanathan V Krishnan, Editor. PLoS One. 2016; 11(12): e0167309. Published online 2016 Dec 1. doi: 10.1371/journal.pone.0167309