ASNase in circulation continuously deaminates Asn with a Km = 29 μM and to a lesser extent Gln with a Km ∼900 μM.2 The hepatic portal vein is the blood vessel that influxes blood via the mesenteric circulation from the gastrointestinal tract and spleen to the liver. This blood is rich in nutrients that have been extracted from food, like amino acids, Asn, Gln, etc.2 The liver processes these nutrients; adipose tissues also provide Gln.10 The liver also synthesizes Asn de novo from Gln aspartate and ATP, a reaction catalyzed via ASNS.2 The sum of the Asn sources is described biochemically as maximum input (Imax) into circulation. Therefore, an effective ASNase must deplete not only Asn but also Gln to reduce the ASNS contribution of Asn biosynthesis.2 Most importantly, in rapidly proliferating malignant cells, Gln and Asp are used as precursors of -N-C- links in the de novo nucleoside biosynthesis. Therefore, depletion of Gln by an ASNase with glutaminase coactivity contributes to the inhibition of protein and DNA biosynthesis. Professional illustration by Marie Dauenheimer.

ASNase in circulation continuously deaminates Asn with a Km = 29 μM and to a lesser extent Gln with a Km ∼900 μM. The hepatic portal vein is the blood vessel that influxes blood via the mesenteric circulation from the gastrointestinal tract and spleen to the liver. This blood is rich in nutrients that have been extracted from food, like amino acids, Asn, Gln, etc. The liver processes these nutrients; adipose tissues also provide Gln.10  The liver also synthesizes Asn de novo from Gln aspartate and ATP, a reaction catalyzed via ASNS. The sum of the Asn sources is described biochemically as maximum input (Imax) into circulation. Therefore, an effective ASNase must deplete not only Asn but also Gln to reduce the ASNS contribution of Asn biosynthesis. Most importantly, in rapidly proliferating malignant cells, Gln and Asp are used as precursors of -N-C- links in the de novo nucleoside biosynthesis. Therefore, depletion of Gln by an ASNase with glutaminase coactivity contributes to the inhibition of protein and DNA biosynthesis. Professional illustration by Marie Dauenheimer.

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