Faculty Research 1990 - 1999

Title

Peptides, enzymes and obesity: new insights from a 'dead' enzyme.

Document Type

Article

Publication Date

1999

Keywords

Carboxypeptidases, Infertility, Membrane-Proteins, Obesity, Peptides, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Trends Biochem Sci 1999 Oct; 24(10):390-3.

Grant

K02DA00194/DA/NIDA, PO188911

Abstract

The identification of the fat mutation, which causes obesity in mice, as a defect in carboxypeptidase E (CPE) has raised more questions than answers. CPE is required for the processing of numerous neuroendocrine peptides and a mutation that inactivates CPE was predicted to be lethal. However, Cpe(fat) mutated mice live and become obese. So, why are mice with the Cpe(fat) mutation viable, and why does obesity develop as a consequence of the pleiotropic effects of this mutant allele? Recently, several new members of the carboxypeptidase family have been discovered, of which at least one, CPD, can partially compensate by contributing to neuroendocrine peptide processing. Obesity due to the Cpe(fat) mutation is not caused by increased food consumption but, rather, is a result of defective nutrient partitioning, the exact mechanism of which remains to be elucidated.

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