Metabolism of enterostatin in rat intestine, brain membranes, and serum: differential involvement of proline-specific peptidases.
The degradation of enterostatin (VPDPR), a potent inhibitor of food intake, by intestinal brush-border membranes, brain membranes, and rat serum has been investigated in the presence of specific inhibitors. Hydrolysis by intestinal membranes was found to be 10 and 100 times faster than in serum and brain membranes, respectively. Enterostatin hydrolysis by intestinal and brain membranes involves the removal of C-terminal arginine by carboxypeptidase P, leading to the production of des-Arg-enterostatin, and the splitting of the Pro2-Asp3 bond by dipeptidyl aminopeptidase IV (DPP IV). A small amount of the potent anorectic peptide Pro2-Asp3-Pro4 was released during hydrolysis of des-Arg-enterostatin by brain membranes and rat serum. In rat serum, enterostatin degradation was mainly due to DPP IV.
Bouras
M
M
INRA, Unité de nutrition Humaine et Physiologie Intestinale, Faculté de Pharmacie, Paris, France.
Huneau
J F
JF
Luengo
C
C
Erlanson-Albertsson
C
C
Tomé
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D003089:Colipases / Q000097:blood / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004792:Enzyme Precursors; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011392:Proline; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity
D003089:Colipases; D004792:Enzyme Precursors; D009842:Oligopeptides; D011498:Protein Precursors; D015842:Serine Proteinase Inhibitors; C095264:enterostatin, des-Arg-; C037107:procolipase; D011392:Proline; C025427:carboxypeptidase P; D002268:Carboxypeptidases; D018819:Dipeptidyl Peptidase 4