Hepatic regulation of plasma L-asparagine.

WOODS, JAMES S., AND ROBERT E. HANDSCHUMACHER. Hepatic regulation of plasma L-asparagine. Am. J. Physiol. 224(4): 74-O-745. 1973.-The hepatic regulation of plasma L-asparagine (Asn) was studied in isolated perfused rat livers. The Asn concentration in the perfusate is rigorously maintained by this organ at 20 PM. Attempts to deplete tissue Asn, normally 500 nmoles/g, by four 1 -hr perfusions with Asn-free perfusate (100 ml) resulted in increased tissue levels (25 %) and did not reduce the continuous contribution of Asn to the perfusate. Inhibition of Asn biosynthesis with 6-diazo-5-oxo-L-norleucine (DON) (10 mu) did not affect the regulation of the perfusate Asn concentration but permitted depletion of tissue Asn to 72 and 42y0 of control levels after two and four I-hr perfusions, respectively. Conversion of aspartic acid -14C to Asn occurred when livers were perfused with Asn-free perfusate or 20 m Asn but not with 200 PM Asn or 10 mu DON. 2,4-Dinitrophenol (0.5 mu) and substitution of choline for Na+ in the perfusate inhibited the influx of Asn by the liver but did not reduce the release of Asn into the perfusate. Thus, de novo Asn synthesis in rat liver is regulated by the concentration of Asn in the perfusate. Asparagine synthetase plays an important role in maintaining the hepatic Asn pool but does not function directly in the exchange of Asn with the perfusate. The latter process appears to involve both active and passive transport mechanisms which, together with Asn synthesis and metabolism, rigorously maintain constant Asn levels in the hepatic and plasma pools.