Ah, halogen groups, they are by far my favorite way of turning regular ordinary molecules into bubble gum chewing, ass kicking molecules that just ran out of bubble gum. Just stick a chloride, bromide or a fluoride onto an everyday molecule and living things don’t really know how to process it. Like DDT or Splenda.
5-Fluorouracil or 5-FU was a regular old RNA nucleotide, uracil, until science attached a fluoride onto the 5th carbon. After that it was a cell killing menace.
5-FU works in a couple different ways. The most important way 5-FU works is by gumming up the enzyme thymidylate synthase. Excuse me if I geek out in organic chemistry, but this is where I think it starts to get interesting.
Thymidylate synthase is responsible for sticking a phosphorous group onto thymine. Eventually, Thymine will get three phosphate groups and a sugar and become a DNA nucleotide, one of the building blocks of DNA. Now another name for Thymine is 5-methyluracil. 5-methyluracil and 5-fluorouracil are a lot a like. So much so that 5-fluorouracil can bind onto thymidylate synthase. (For those of you that studied enzyme kinetics, I don’t know if the reaction is an example of competitive or suicidal inhibition.) Because 5-FU is inhibiting the enzyme, thymidylate synthase can’t make DNA nucleotides that the cell needs for repair or division. DNA synthesis comes to a halt and the cell dies, which is good cause we’re talking about cancer here.
Where it gets a little neat, and naturopathic, is thymidylate synthase depends on folic acid to work. Without folic acid, thymidylate synthase isn’t going to bind to 5-FU, and it’s not going to bind to thymine to make DNA nucleotides. A fairly standard practice is to give 5-FU with leucovorin, which is a form of folic acid, because giving leucovorin makes 5-FU more effective at killing cancer cells. To me, that implies that the people who have benefit from leucovorin don’t have enough folic acid to run all of their metabolic pathways at 100%. It makes me want to assume people who get the kind of cancers that 5-FU is used to treat, colon, pancreatic and breast, are deficient in folic acid or have genetic errors in folic acid metabolism.
MTHFR SNPs…excellent work.