Mitochondrial ceramidase

Figure 2. Alignment of the human mitochondrial ceramidase to homologous ceramidases from various organisms. Sequences of ceramidases were aligned using ClustalW algorithm of the Mac Vector program. Amino acids identical are shaded in grey and consensus residues are shown under the alignment. Amino acids of the same group are shaded in white.

The terminal hydroxy group of ceramide has also been modified. 1-0-Methoxyceramide did not inhibit mitochondrial ceramidase (69), and 1-fluoroceramide was a weak inhibitor of glucosylceramide formation in cultured murine neuronal cells (80). The 1-methylthio analog of dihydroceramide activated sphinganine kinase and dismpted neuron axonal growth in cell cultures (81). 

As discussed above, altering the stereochemistry of the sphingosine backbone has produced, in many instances, stereoisomers with altered bioactivity compared with the natural stereoisomer, for example, in activating the catalytic subunit of serine-threonine protein phosphatase 2A (63) or in inhibiting mitochondrial ceramidase (69). 

A. Structural requirements of ceramide and sphingosine based 86. inhibitors of mitochondrial ceramidase. Biochemistry 2001 40 9657-9668. 

Usta, J, El Bawab, S, Roddy, P, Szulc, ZM, Hannun, YA and Bielawska, A (2001) Structural requirements of ceramide and sphingosine based inhibitors of mitochondrial ceramidase. Biochemistry, 40, 9657-9668. 

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