Choline pathways during normal and stimulated renal growth in rats.

Abstract

A B S T R A C T Celluilar membrane synthesis ocecurs during normal and stimutlated renal growNth. Choline in the kidney is utilized as a precuirsor for membrane synthesis via the choline kinase reaction. We investigated choline phosphorylation dturing normal and stimulated renal growth. Rapidly growing neonatal rat kidneys contained relatively high levels of choline kinase activity (61 pmol phosphoryleholine/min per mg protein). Choline kinase activity and phosphorvlcholine production then fell gradually over the 1st mo of life; by 1 mo phosphorylcholine produiction was 34 pmol phosphorylcholine/min per mg protein. Choline kinase activity increased by 27% (P < 0.001) in 28-dayold rats when renal growth was stimtulated by contralateral nephrectomy; the increase occuirred wvithin 2 h after suirgery. Thus, changes in the activity of this important enzyme in the initiation of membrane svnthesis is associated both with normal renal development and with adaptation to nephron loss. The findings further stuggest that the cell membrane may be involved in the initiation of compensatory renal growth.

Reversal of the Normal Pattern of Renal Choline Metabolism during Uremia in Rats

“…3 or 8 weeks later the rats were weighed, venous blood was drawn for serum urea nitrogen and hema tocrit determinations, and their kidneys were removed for analysis of choline kinase activity and choline oxidase activity by our modifica tion of the method of Farrell çt al. [ 1,8], in which the remnant or shamoperated kidneys were immediately homogenized in Tris buffer (pH 7.0)and then incubated with radiolabcllcd methyl ' 'C-cholinechloride (117 \xM, specific activity 57 ¡¿Ci/mmol; New England Nuclear, Boston, Mass.) and ATP [I].…”

“…One of the earliest and well-maintained reactions of this regenerative growth is an alteration in membrane phos pholipid metabolism [1,2]. Choline in the kidney is meta bolized by two major biosynthetic pathways: (I) phos phorylation via choline kinase (EC 2.7.1.32) for incorpora tion into membrane phospholipids [3] and (2) oxidation to betaine for use primarily as a methyl group donor [4].…”

“…Choline in the kidney is meta bolized by two major biosynthetic pathways: (I) phos phorylation via choline kinase (EC 2.7.1.32) for incorpora tion into membrane phospholipids [3] and (2) oxidation to betaine for use primarily as a methyl group donor [4]. Following uninephrectomy in rats, the choline kinase ac tivity and the rate of incorporation of choline into mem brane phospholipids increase markedly in the remaining kidney [1,2], This is followed by a 40% increase in the re maining renal mass within 3 weeks [5] and a return of renal function towards normal.…”

Amino acid modulation of renal phosphatidylcholine biosynthesis in the rat.

“…The microsomal pellet was resuspended in the above solution at a protein concentration of 8-10 mg/ml and was used as an enzyme source. The standard reaction mixture (0.2 ml) contained 25 mM MgCl2, 50 mM KCI, 0.1 M imidazole (pH 8.5), 25 mM DL-dithiothreitol, was unchanged by the addition of these compounds. The reaction was started by the addition of enzyme to the preincublated reactants; After a 4-mmin incubation at 38°C the reactioni was stopped by the addition of chloroform: methanol (2:1, vol:vol) and radioactivity in the lipid extract determined as described (15).…”

“…We previously demonstrated that renal cortical cells from normal rats used the Kennedy pathway for the biosynthesis of phosphatidylcholine, the major renal membrane phospholipid (8). Increased rates of biosynthesis via this pathway have been reported during renal regeneration after acute tubular necrosis (1), potassium depletion nephropathy (8,15,17), and compensatory growth after uninephrectomy (14,25). Phosphatidylcholine biosynthesis during renal regeneration after acute tubular necrosis is augmented by the provision of amino acids in vivo and in vitro (2,3).…”