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Moreover, the H-bond with Arg120 plays a significant role, as suggested by mutational analyses that an interaction of the carboxylate of arachidonic acid with Arg-120 is required for high-affinity binding by COX-1 in its catalytically productive conformation (hydrophobic groove above Ser530) as arachidonic acid is a preferred substrate for COX-1 70
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In the first no-polymorphism phenotype, low folate intake or low FAD availability with normal MTHFR activity, lack of folate-substrate and FAD-cofactor for the MTHFR enzyme, retards both folate and methionine cycles creating an under-methylation setting
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