763 EVIDENCE FOR TWO GENES ENCODING HUMAN ARGINASE

Abstract

Patients missing liver arginase retain considerable capacity to synthesize urea. The mechanism by which this occurs is unknown and previous biochemical and immunologic studies did not distinguish a one from a two-locus model. A kidney biopsy was obtained from M.U., an 11-year-old boy with arginase deficiency. The kidney had a specific activity of 1.34 μmol/30min/mg protein as compared to 0.35-0.87 μmol/30min/mg protein in control biopsy and autopsy kidney. When tested with rabbit anti-human liver arginase (RAHLA), the M.U. kidney demonstrated a line of identity with normal human liver and kidney. RAHLA did not precipitate kidney arginase in M.U., but did precipitate 50% of normal kidney and 100% of normal liver arginase. Precipitation-inhibition experiments demonstrated an antigenic but enzymatically inactive protein in M.U. kidney that cross-reacted with liver arginase. The data support the existence of two arginase genes in man, one expressed in liver (AI) and two in kidney (AI and AII). AI codes for enzyme active in normal liver and kidney, but not in M.U. kidney. M.U. has an inactive AI protein as demonstrated by precipitation-inhibition. All is expressed in normal kidney and in M.U. kidney. All probably arose as a result of gene duplication and appears to be inducible as demonstrated by the high specific activity of arginase in M.U. kidney. The presence of a second arginase gene expressed in kidney explains the ability of arginase-deficient patients to synthesize urea.