Chemistry and biochemistry of 1-desoxysphinganine 1-phosphonate (dihydrosphingosine-1-phosphonate)

The chemical synthesis of labelled 1-desoxy-D,L-sphinganine 1-phosphonate has been elaborated. This compound is an analog of sphinganine 1-phosphate, a naturally occurring intermediate in the biological degradation of long chain bases.The phosphonate is highly toxic when administered intravenously due to its hemolytic effect. The microsomal sphingosine 1-phosphate lyase(aldolase) cleaves 3-³H] 1-desoxysphinganine 1-phosphonate to 1-³H] hexadecanal and aminoethyl phosphonate like sphinganine 1-phosphate however at a reduced rate. The phosphonate is a competitive inhibitor of the lyase (aldolase). K_i has been determined. The molecular dimensions of the phosphonate have been discussed with reference to the aldolase mechanism and known properties of the enzyme.