SAICAR

SAICAR, short for 5-aminoimidazole-4-carboxamide ribonucleotide, is an intermediate in the de novo purine biosynthesis pathway found in bacteria, archaea, and eukaryotes. In this pathway, the substrate CAIR (carboxyaminoimidazole ribonucleotide) is converted into SAICAR by the enzyme SAICAR synthetase (PurC) through the addition of an aspartate moiety. SAICAR is subsequently transformed into AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) by SAICAR lyase (PurB), continuing toward the production of inosine monophosphate (IMP), a key purine nucleotide.

As part of the purine biosynthesis cascade, SAICAR serves as a transient intermediate that links CAIR to AICAR. The enzymes involved, PurC and PurB, are conserved across many organisms, reflecting the central role of purine nucleotide formation in cellular metabolism.

Beyond its metabolic role, SAICAR has been studied for potential regulatory effects on cellular metabolism. Some research suggests that SAICAR can act as an allosteric activator of pyruvate kinase M2 (PKM2), which may connect nucleotide biosynthesis with glycolytic flux in certain cancer cells. The physiological relevance of this interaction remains an area of active investigation and may vary by context.

The name SAICAR derives from its chemical structure as a ribonucleotide with an imidazole ring bearing a carboxamide group. In normal metabolism, SAICAR is a short-lived intermediate that is rapidly converted as purine biosynthesis proceeds.