Intragenic complementation and the structure and function of argininosuccinate lyase
- Cite this article as:
- Yu, B. & Howell, P. CMLS, Cell. Mol. Life Sci. (2000) 57: 1637. doi:10.1007/PL00000646
- 325 Downloads
Argininosuccinate lyase (ASL) catalyzes the reversible hydrolysis of argininosuccinate to arginine and fumarate, a reaction important for the detoxification of ammonia via the urea cycle and for arginine biosynthesis. ASL belongs to a superfamily of structurally related enzymes, all of which function as tetramers and catalyze similar reactions in which fumarate is one of the products. Genetic defects in the ASL gene result in the autosomal recessive disorder argininosuccinic aciduria. This disorder has considerable clinical and genetic heterogeneity and also exhibits extensive intragenic complementation. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits greater enzymatic activity than is found in either of the homomeric mutant proteins. This review describes the structure and function of ASL and its homologue δ crystallin, the genetic defects associated with argininosuccinic aciduria and current theories regarding complementation in this protein.