Adenosyl homocyteinase is a methyl group transferring enzyme that is inhabited by copper in the +2 oxidation state. We were trying to better understand the process of gene silencing by methylation, see below. In the process we discovered the mechanism of how +2 oxidation state copper might be bad for our hearts.
Some UniProt.org highlights
UniProt.org is a site scientists consult to learn more about proteins. This is where it was discovered that
Adenosylhomocysteinase (SAHH protein, ACHY gene) catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine. Hydrolysis is the use of a water molecule (H2O) to cleave the first molecule into two new molecules. One molecule gets an “H” and the other gets an “OH.” According to the AI written UniProt blog SAH binds copper ions (By similarity). NAD+ is also a cofactor. The copper part of the story deserves some followup by a PubMed search or simply going to the PubMed that the AI program left us with.
This is the reference to the actual scientific study.
Li M, Li Y, Chen J, Wei W, Pan X, Liu J, Liu Q, Leu W, Zhang L, Yang X, Lu J, Wang K. Copper ions inhibit S-adenosylhomocysteine hydrolase by causing dissociation of NAD+ cofactor. Biochemistry. 2007 Oct 16;46(41):11451-8. PubMed
This study demonstrated that Cu2+ bound to SAHH and decreased its affinity for cofactor NAD+.
Back to the SAHH products and reactants
Things are tricky here because our Cu(II) inhbited wenzyme SAHH can go in both directions. Many readers may recognize the products/reactants as substances used in diagnostic blood tests.
Adenosine acts on receptors in our blood vessels that might increase blood flow. It is also used in medical tests of our heart function. According to the Cleveland clinic homocysteine can indicate an increased risk for cardiovascular disease. According the Health Matters S-adenosylhomocysteine is also used as a risk factor for cardiovascular disease. Health Matters references peer reviewed publications stating that S-adenosylhomosysteine may be a more sensitive marker than homosysteine because the former can inhibit DNA methylation enzymes that turn genes off. DNA methylation can turn good genes off too.
SAHH and turning genes off.
This post is not going to explore the scientific study related to this image. Putting methyl groups on the promoter of a gene prevents the gene from being transcribed into messenger RNA that gets translated to protein by our ribosomes. While we know that Cu(II) inhibits one enzyme , SAHH, in this process, we do not know what the impact, if any, of consuming Cu(II) will have on DNA methylation.
This post is not meant to say that taking a Cu(II) will inhibit this cycle. If one is to take a copper supplement maybe, just maybe,a Cu(I) might be better.