Peroxynitrite can be scavenged by “uric acid”, which is the most abundant antioxidant in our blood. However, research shows that patients with MS have significantly lower levels of uric acid, as the following studies confirm. In the first study the researchers concluded that lower uric acid levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide.
Serum uric acid and multiple sclerosis.
Rentzos M, Nikolaou C, Anagnostouli M, Rombos A, Tsakanikas K, Economou M, Dimitrakopoulos A, Karouli M, Vassilopoulos D. 2006. Clin Neurol Neurosurg. 108(6):527-31. Epub 2005 Oct 3.
“Peroxynitrite (PN) has been implicated in multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis…In the overall MS group, patients were found to have significantly lower mean serum uric acid levels…Our findings suggest that lower serum UA levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide…”
In the next study the researchers stated that peroxynitrite exerts a toxic effect on neurons, axons, and glia cells and increases the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in experimental allergic encephalomyelitis. The study authors concluded that uric acid levels in MS patients were lower than in controls. In addition, patients with active disease had lower levels than those in remission.
Uric acid and multiple sclerosis.
Mattle HP, Lienert C, Greeve I. 2004. Ther Umsch. 61(9):553-5.
“Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE…Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission…At present, uric acid can solely be regarded as a marker of disease activity in MS...”
In the following study the researchers confirmed the role that uric acid plays in scavenging peroxynitrite and the significantly lower levels of uric acid found in patients with MS. In addition, the researchers stated that statistical evaluation of more than 20 million patient records for the incidence of MS and gout, which is caused by high levels of uric acid, revealed that the two diseases are almost mutually exclusive.
Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis.
Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H. 1998. Proc Natl Acad Sci USA. 95(2):675-80.
“Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger…A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS…”
The significantly lower levels of uric acid found in patients with MS can be clearly explained by a lack of the pancreatic enzyme DNase 1 (deoxyribonuclease). Uric acid is the final breakdown product of dietary DNA. DNase 1 is the enzyme responsible for the breakdown of dietary DNA. An inability to digest dietary DNA, due to a lack of DNase 1, would lead to low levels of uric acid.
Here is a link and some information from a site that explains this quite clearly. I hope the link opens for everyone. It would open on one of my computers, but not on another (something about the browser). Also, there is a really great graph if anyone can figure out how to post it (I tried, really I did). https://www.inkling.com/read/illustrate ... -of-purine
Degradation of Purine NucleotidesDegradation of dietary nucleic acids occurs in the small intestine, where a family of pancreatic enzymes hydrolyzes the nucleic acids to nucleotides.
Inside the intestinal mucosal cells, purine nucleotides are sequentially degraded by specific enzymes to nucleosides and free bases, with uric acid as the end product of this pathway."
Degradation of dietary nucleic acids in the small intestine
Ribonucleases and deoxyribonucleases, secreted by the pancreas, hydrolyze dietary RNA and DNA
primarily to oligonucleotides.Oligonucleotides are further hydrolyzed by pancreatic phosphodiesterases, producing a mixture of 3′- and 5′-mononucleotides. In the intestinal mucosal cells, a family of nucleotidases removes the phosphate groups hydrolytically, releasing nucleosides that are further degraded to free bases. Dietary purine bases are not used to any appreciable extent for the synthesis of tissue nucleic acids. Instead, they are generally converted to uric acid
in intestinal mucosal cells. Most of the uric acid enters the blood, and is eventually excreted in the urine.