Many of these posts are slowly being moved to the
MTHFR site
that includes MTHFR, glutatione and sulfur cycle as well as methylation
Sulfur in biological systems is usually associated with the redox status regulating small molecule. Sulfur containing small molecules are also involved in methyl transferase reactions that we call epigenetics. Inorganic sulfur transporters may also be compromised by toxins. Transsulfuration is also involved in production of the ATP back up molecule creatine/creatine phosphate.
B6, pyridoxal phosphate family
B6 and transsulfuration…There is a connection between a sulfur salvage pathway enzymes: S-adenosyl homocysteine hydrolase and Cystathionine beta-synthase with vitamin B6 as a cofactor. Both might be impacted in autism spectrum of disorders. Perhaps there is a connection in all of us. This post is what happens when one sits down with a collection of publications and asks, “How are these papers related?”
H2S therapy...This post was inspired by a review on fatty liver disease that listed four enzymes responsible for H2S production. One of these four is Cystathionine beta-synthase with vitamin B6 as a cofactor
Thiamine and pyridoxal kinase .. This post started out examining what seemed like a fantastic report that thiamine, aka vitamine B1 can bind to and modulate the activity and phosphorlation status of the pyridoxal (vitamin B6) family of vitamers. Then we discovered that thiamine’s thiol can become a protein modifying thiolate anion and can modify PdxK.
Copper (II) and homocysteine describes a deleterious interaction between copper in the +2 oxidation state with homocysteine. This is something I discovered working with Dr J that related to my work with Mitosynergy.
B12
B12 and glutathione ...This post explores the relationship between thiols and cobalamin/B12 and their relationship to autism, schizophrenia, and aging,
B12 and Nrf2 …. The post was originally going to focus on a study postulating that decreased Nrf2 expression is at the root of messed up B12/cobalamin species and thiol status in autism. The ins and outs of the NFE2L2 promoter are examined. This post will conclude that increasing production of the Nrf2 protein will help more humans than just those with autism. Nrf2 expression correlates with B12/cobalaminin
Alpha-lipoic acid and Nrf2…This post was inspired by a health care guru of sorts who harped upon the wonders of NRF2 and all of the genes it controls the transcription of. The transcription factor Nrf2 and its redox sensitive keeper Keap1 have been covered in a post on ozone therapy. This post points to Nrf2 as the mediator of α-LA protection against As, Hg, and Cd toxicity and GSH synthesis as an important part of the protection.
Ozone therapy…This post explores the interaction between ozone therapy and the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) transcription factor. The Wikipedia author failed to understand fundamentals of how low levels of a toxin can be protective. As the post suggests, the real crux of this post is how ozone might react with thiols in a protein called Keap1 that targets the transcription factor Nrf2 for degradation. This post will direct the reader to some good reviews regarding ozone therapy. The take home message is that we have a very good idea of how ozone therapy might be working even if governments have so far failed to fund the research to take ‘quackery” to an established medical science.
B12 and B9 …A theme of this post is that B12 (cobalamin Cbl) and and B9/folic acid are partners in many metabolic pathways that involve transfer of single carbons, or methyl groups, from one molecule to another.
Methylation
The biochemistry of methylation …This post covers what DNA methylation is and some enzymes that control this process. What could be their role in autism?
changing the epigenome..This post is an overview of modifications of proteins and DNA that control the translation of genes into messenger RNA to make proteins. This process is tied to thiol redox status.
histone methylation and more .. We were interested in the difference between methylation and acetylation and how they control histone function. Then histone propionation was discovered. This links back to our interest in short chain fatty acids!
maternal vs paternal methylation of DNA … This post explores maternal vs paternal gene methylation. Some comments on thiol status and reactive oxygen species are given in the conclusion.
Transporting inorganic sulfur
Na sulfate transporter… This post explores heavy metal inhibition of the sodium sulfate cotransporter (NaSi1 / Slc13a1as well as genetic variants affecting activity. This post also introduces the sulfate/anion transporter SaT1/Slc26a1.
glyphosate and thiols …This post covers an exciting proteomics study that suggests a mechanism of glyphosate toxicity by which the metabolite glyoxylate reacts with protein thiols thereby damaging fatty acid modifying enzymes. To make matters more interesting the sulfate/oxylate transporter slc26a1 also transports glyoxylate. For all of those who have noted a sulfate connection in autism and have wondered about environmental toxins like glyphosate.
Senoff Samel Kosmotrophes Senoff and Samel have published numerous Rachel Carson style reviews on the issues with the herbicide glyphosate. We were concerned that the phosphate in glyphosate might have kosmotrophe activity and inhibit an important transporter of sulfate in our bodies. This post defines what it means to be a kosmotrophe.
renal (sulfate) transporters … NaS1 also known as slc13a1 is the sodium coupled sulfate transporter thatdepends n the electro chemical gradient of Na+ . SAT1 is a passive sulfate anion exchanger that is also known as Slc26a1. The goal was to figure out which part of the renal tubule these transporters are located and what other transporters are present.
oral sulfate transporters…A subtitle to this post is “Saliva sulfate is not a good surrogate for serum sulfate.” The very strange twist is that there are plenty of sulfate transporters along the dental line that may or may not be acting as sulfate transporters. This brings us back to the oral microbiome and a previous post on the mouth brain axis.
Creatine
Creatine phosphate is an energy reserve molecule just like ATP. It connects to the methionine cycle which is connected to the folic acid methylation cycle. Guanidinoacetate methyltransferase (GAMT), the enzyme that converts GAA to creatine, has ASD associated SNPs
Arginine L-arginine is being used as a sports supplement – What is the connection to creatine? It and glycine are reactants in the production of creatine via GAA. Some clinical trials with l-arginine are reviewed. Arginine’s place in biochemical pathways is also presented.
Creatine and bacteria This post explores how creatine is metabolized by bacteria and may affect the microibiome. However the Slc6A8 creatine transporter may remove small or moderate doses of oral creatine before they reach the colon.
Hypothetically we can absorb small doses of creatine before our microbiome even sees it.
creatine and asthma … Some clinical trials are discussed that suggest that creatine supplementation exacerbates asthma. Extracellular creatine kinase seems to be a possible explanation.
creatine kinase…ome of the peer reviewed literature concerning creatine kinase makes very little sense from a functional standpoint. This post was originally geared towards a set of biomarkers that differentiate ASD from neuro typical. We need an understanding of creatine kinase does when it is extracellular and ask slightly different questions, in my opinion. One would think that if the creatine dose is moderate it will not be available to snatch high energy Ps from ATP to produce ADP.