Metabolism of arginine in lactating rat mammary gland

Abstract

Significant activities of the four enzymes needed to convert arginine into proline and glutamate (arginase, ornithine aminotransferase, pyrroline-5-carboxylate reductase and pyrroline-5-carboxylate dehydrogenase) develop co-ordinately in lactating rat mammary glands in proportion to the increased production of milk. No enzymes were detected to carry out the reactions of proline oxidation or reduction of glutamate to pyrroline-5-carboxylate. Minces of the gland converted ornithine into proline and into glutamate plus glutamine. These conversions increased during the cycle of lactation in proportion to the increased milk production and to the content of the necessary enzymes. The minced gland did not convert labelled ornithine into citrulline, confirming the absence from the gland of a functioning urea cycle, and did not convert labelled proline or glutamate into ornithine. A metabolic flow of labelled arginine to proline and glutamate in mammary gland was confirmed in intact animals with experiments during which the specific radioactivity of proline in plasma remained below that of the proline being formed from labelled arginine within the gland. It was concluded that arginase in this tissue had a metabolic role in the biosynthesis of extra proline and glutamate needed for synthesis of milk proteins.

Arginine metabolism: nitric oxide and beyond

“…As shown in Figure 5, P5C can subsequently be utilized for synthesis of proline or glutamate. OAT, P5C reductase and P5C dehydrogenase activities are present in a wide range of tissues [248], indicating the potential for synthesis of both proline and glutamate, but little is known regarding the relative usage of P5C by these two pathways in different cells, with the exception of the small intestine [193] and the mammary gland [249].…”

“…The output of proline in the milk of goats [255], sheep [256], cows [257] and pigs [258] greatly exceeds the uptake of proline by the lactating mammary gland, whereas the uptake of plasma arginine by lactating mammary glands greatly exceeds the output of arginine in the milk [255][256][257][258][259]. Studies with lactating mammary tissues have demonstrated arginine-dependent production of proline [249,257], but there was little or no synthesis of proline from glutamate [249] because of the absence of P5C synthetase [47,249]. Uptake of ornithine and citrulline (potential precursors for proline synthesis) by the lactating mammary gland is relatively low compared with that of arginine [256,257].…”

“…Uptake of ornithine and citrulline (potential precursors for proline synthesis) by the lactating mammary gland is relatively low compared with that of arginine [256,257]. There is virtually no proline catabolism by the mammary gland because it lacks proline oxidase [249]. Consequently there is a relative enrichment of proline and a relative deficiency of arginine in milk protein [57,260].…”

“…Consequently there is a relative enrichment of proline and a relative deficiency of arginine in milk protein [57,260]. The enzymes required for the synthesis of proline from arginine (arginase, OAT and P5C reductase) are present in the mammary gland [249,261,262], and activities of these enzymes are co-ordinately induced during development of the lactating mammary gland [249,261]. The major isoenzyme of arginase in the mammary gland is type II [262,263], which is co-localized with OAT in the mitochondrion.…”

A sensitive assay for ornithine amino transferase in rat brain mitochondria by ninhydrin method

“…Physiological concentration of ornithine inhibit P5C synthase; thus, high concentrations should favour the OAT mediated pathway of proline synthesis (18). For example, in hormonally stimulated rat mammary gland, Arginase, OAT and P5C reductase activities increase co-ordinately in response to hormonal stimulation and arginine is a major biosynthetic precursor for the proline used in milk protein synthesis (19).…”