Aminoadipic semialdehyde

Requena, J.S., Chao, C.-C., Levine, R.L., and Stadtman, E.R. (2001) Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proc. Natl. Acad. Sci. 98, 69-74. 

In mammals a single PPTase is used for the posttranslational modification of three different apo-proteins the carrier proteins of mitochondrial and cytosolic FASs and the aminoadipate semialdehyde reductase implicated in lysine degradation. The crystal structure of human PPT ase has been determined and found to be most closely related to the class II Sfp-like enzymes. Architectural and mechanistic differences between the type II human PPTase and the type I bacterial PPTases include a divalent cation coordinated by the a-phosphate of CoA, a Glu and an Asp residue, and three water ligands in type I PPTases versus a divalent cation coordinated by a- and /3-phosphates of CoA, two to three protein side chains, and a water molecule in the human PPT ase. 

AASA a-aminoadipic semialdehyde, AdoHcy S-adenosylhomocysteine, AdoMet S-adenosylmethionine, Ala alanine, Arg arginine, alle alloisoleucine, Apo aminopiperidone, ASA argininosuccinate,... 

Hyperlysinemia a-Aminoadipic semialdehyde dehydrogenase Seizures, mental retardation, lack of muscle tone, ataxia ... 

Lysine tyrosylquinone (LTQ) (Figure 3) is the protein-derived cofactor of mammalian lysyl oxidase, an important enzyme in the metabolism of connective tissue. Lysyl oxidase catalyzes the posttranslational modification of elastin and collagen. It oxidizes selected peptidyl lysine residues to peptidyl a-aminoadipic -semialdehyde residues. This initiates formation of the covalent cross-linkages that insolubilize these extracellular proteins. This enzyme also contains copper as a second prosthetic group. 

Most prokaryotes employ dedicated PPTs active toward specific apoprotein substrates. Fungi also utilize separate PPTs for modification of the ACPs associated with the cytosolic and mitochondrial FAS systems, as well as the a-aminoadipate reductase involved in lysine biosynthesis [8]. The former is unusual in that it is a constituent domain of the multifunctional a-subunit (Fig. 4). Surprisingly, animals appear to employ a single PPT for servicing three different apoproteins the ACP domain of the cytosolic FAS, the ACP component of the mitochondrial FAS, and the a-aminoadipate semialdehyde dehydrogenase involved in lysine catabolism. The human PPT has recently been identified and characterized (S. Smith, 2003) and its crystal structure determined in complex with Mg, CoA, and the ACP domain of the cytosolic FAS (Structural Genomics Consortium). The ACP domain is comprised of a four-helix bundle, as are the ACPs associated with type II systems. The conserved serine residue that is the site of posttranslational modification lies at the N-terminal end of helix-2 (Fig. 6B), closely juxtaposed with the pyrophosphate of CoA that is cleaved during the phosphopantetheine transfer. Helix-2 makes multiple... 

I Homocitrate synthase 2 homocitrate dehydratase 3 homoaconitate hydratase 4 homoisocitrate dehydrogenase 5 2-aminoadipate aminotransferase 6 aminoadipate semialdehyde dehydrogenase 7 saccharopine dehydrogenase (L-glutamate forming) 8 saccharopine dehydrogenase (L-lysine forming)... 

Aminoadipic semialdehyde synthetase deficiency Fibroblasts, liver, heart, kidney ... 

Table 12.2 a. 2-Aminoadipic semialdehyde synthase deficiency (hyperlysinemia I) (less than 20 patients known) ... 

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