The Substrate Specificity of Pantethinase

Abstract

The substrate specificity of pantethinase, the mammalian enzyme which has been isolated from horse kidney cortex, has been studied. The real substrate has been found to be pantetheine in the reduced form, and the involvement of one or more -SH groups of the enzyme is also considered.A number of other compounds, chemically related t o pantetheine, has also been tested as substrates. Pantethinase is able to metabolise pantetheine-4'-phosphate, with an activity about loo/, of that exhibited for pantetheine ; it is inactive on the other substances tested (pantothenoylcysteine-4'-phosphate, pantothenoylcysteine, pantetheine thiazoline, CoA).The metabolic role of pantethinase seems to be, in the light of the above results, connected with a degradative pathway of pantetheine-4'-phosphate, which is known to be one of the intermediates in the biosynthesis of CoA.A series of studies on the metabolism of cysteamine led to the identification of a new hydrolytic enzyme, which metabolises pantethine yielding pantothenic acid and cystamine, by cleavage of one of the carboamide bonds [l, 21. This enzyme, called pantethinase, is activated in the presence of cysteine (or other thiols as well), which increases enzymatic activity; nevertheless in the absence of any added thiol a little activity can be detected. To explain this behaviour two alternative hypotheses are possible : either the real substrate of the enzyme is the reduced form of pantethine or the enzyme requires the presence of reduced -SH groups in its molecule for fully catalytic activity. I n both cases the enzyme could show a little activity also in the absence of any activator, as actually observed, since the sulphidedisulphide exchange between the substrate molecule in the oxidized form and free -SH groups of the protein (or other contaminant proteins as well) could give rise to the active form(s). Of course, it can not be excluded a t all that both hypotheses are true a t the same time.

The Transcription Factors Steroidogenic Factor-1 and SOX9 Regulate Expression of Vanin-1 during Mouse Testis Development

“…7. Vanin-1 is one of a class of enzymes responsible for the catabolism of pantetheine, formed during degradation of coenzyme A (CoA), to produce pantothenate (vitamin B5) and cysteamine (36,37). Pantothenate is converted to CoA by a crucial biosynthetic pathway.…”

Metabolism of Pantethine in the Rat

“…The PISS-splitting activity in the intestinal mucosa evidenced here seems to be involved in this dissimilative reaction. The PTSS-splitting activity was reported to be distributed also in the liver and the kidney of rats (4,7,8) and to be located in lysosomes and microsomes of these tissues and in the cytoplasmic fraction of the kidney (4). This enzyme, a specific amidohyd rolase, was described as contributing to the dissimilation of CoA in the cells of these tissues (4).…”

“…When administered parenterally to rats having a reduced CoA level, panteth(e)ine can more efficiently restore the hepatic CoA level than pantothenate (5,6). On the other hand, it has been reported that panteth(e)ine undergoes in vitro hydrolysis to pantothenic acid with jS mercaptoethylamine as another product by the action of a specific amidohyd rolase, one of the member enzymes involved in the metabolic dissimilation of CoA (4,(7)(8)(9).…”

Pantetheinase Activity and Cysteamine Content in Cystinotic and Normal Fibroblasts and Leukocytes

“…This degradative pathway permits cysteamine generation and pantothenate recovery. Enzymatic degradation of CoA was described by Lipmann et al and Novelli et al (25) and subsequent important studies related to pantetheine catabolism have been performed by Dupre et al (using horse kidney) (4,6,8,11,(13)(14)(15)(16)(17) and Abiko et al (rat liver and kidney) (1)(2)(3)26,36). In rat liver, CoA is degraded to phosphopantetheine by a lysosomal acid phosphatase and a nuclear and microsomal plasma membrane pyrophosphatase.…”

“…To test lysosomal membrane should be permeable (33) and hence could this we have for measur-be the fundamental etiology of abnormal cysthe accumulation in ing pantetheinase (cysteamine-generating) activity and intracellu-cystinosis. lar cysteamine levels and used these methods to measure such Cystearnine ( (4,6,8,9,(14)(15)(16)(17). 9.4 f 1.5; cystinotic, 7.7 2 1.71.…”