L-leucine, a specific inhibitor of a rare human placental alkaline phosphatase phenotype

Abstract

FISHMAN et al. reported that human placental alkaline phosphatase (Regan isoenzyme) was found in the serum and tumour tissue of a patient with lung cancer¹. Two electrophoretically different variant forms of Regan alkaline phosphatase with a greater sensitivity to inhibition by L-leucine have since been described: the ‘Nagao isoenzyme’², and a hepatoma-specific alkaline phosphatase^3–5. Inglis et al.⁶ reported that the L-leucine-sensitive Nagao isoenzyme found in some cancer patients closely resembled the ‘D variant’ of human placental alkaline phosphatase, a rare phenotype defined electrophoretically on starch gel which is found in less than 1% of the general population of pregnancies⁷. An example was reported of a pregnancy serum D-phenotype enzyme presumably of placental origin, confirmed by electrophoresis established as L-leucine-sensitive⁶. Most interesting was the occurrence of the variant at high frequency in the ovarian cancer patients surveyed^6,8. To extend the observations of Inglis et aL, screening for the phosphatases in placentae was carried out, both to establish the frequency of the L-leucine-sensitive placental phenotypes (which should match the frequency of the electrophoretically defined D variant phenotypes) and to provide enough enzyme to enable purification and characterisation. Supply of cancer tissue is generally restrictive for this purpose.