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J Biol Chem. 1984 May 25;259(10):6459-65.

Rat liver and small intestine produce proapolipoprotein A-I which is slowly processed to apolipoprotein A-I in the circulation.


Two-dimensional electrophoretic analysis of plasma lipoproteins from male Osborne-Mendel rats consistently reveals three isoforms of apolipoprotein A-I (apo-A-I) with the following apparent pI values and quantitative distribution: isoform 3, pI = 5.68, 69%; isoform 4, pI = 5.55, 29%; isoform 5, pI = 5.44, 2%. The two major isoforms were obtained by preparative isoelectric focusing and subjected to NH2-terminal amino acid sequence analysis with the following results: isoform 3, (Asp)-Glu-Pro-Gln-Ser-Gln-Trp-Asp-Arg-Val; isoform 4, X-Glu-Phe-X-Gln-Gln-Asp-Glu-Pro-Gln-Ser. By comparison with the amino acid sequence previously reported for the primary translation product of rat intestinal apo-A-I mRNA (Gordon et al. (1982) J. Biol. Chem. 257, 971-978), isoform 3, the more basic isoform, is identified as mature apo-A-I and isoform 4 as its proform ( proapo -A-I). The proform differs from mature apo-A-I by a 6-amino acid extension at the NH2 terminus. Isoform 5 was not identified further. The plasma steady state distribution of the apo-A-I forms indicates that proapo -A-I is relatively stable in the circulation. Virtually all plasma proapo -A-I is lipoprotein-associated. No significant differences in the steady state proportions of plasma apo-A-I forms were observed between male and female rats, or among various subfractions of plasma high density lipoproteins obtained by heparin-Sepharose affinity chromatography or by density gradient ultracentrifugation. Rats fed a high fat, high cholesterol diet, however, showed an increase in the proportion of circulating proapo -A-I. The relative increase in proform was even more pronounced in rats fed a fat-free diet containing orotic acid. The biosynthesis, secretion, and metabolism of the various apo-A-I forms were also studied. In liver and intestine, the only known sites of apo-A-I synthesis in the rat, approximately 85% of the newly synthesized intracellular apo-A-I, was the proform . Proapo -A-I was also the predominant form (approximately 80%) released into the circulation by isolated, perfused livers and by autoperfused intestinal segments in vivo. Gradual processing of circulating proapo -A-I to mature apo-A-I was observed in vivo following pulse-labeling of apo-A-I with [3H]leucine. Processing in vivo was approximately 80% complete in 10 h.(ABSTRACT TRUNCATED AT 400 WORDS).

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