Type Natriuretic Peptide

BNP is a predominantly cardiac-derived, cyclic 32 amino acid polypeptide with a high degree of primary structure homology with ANP (2) (Fig. 1). Human BNP is encoded by a single-copy gene located on chromosome 1 consisting of three exons and two introns (48,49). The posttranslational processing of the BNP precursor gene seems to differ from that of the human ANP precursor, and the processing of proBNP to NT-proBNP and the 32 amino acid biologically active BNP is less well defined than for proANP. In vitro experiments have suggested that the proteolytic enzyme furin is responsible for specific cleavage of proBNP into the N- and C-terminal fragments (50). However, a family of peptides is derived from the BNP gene (51,52). In human cardiac tissue, BNP appears to be found predominantly in the 32 amino acid form, but a significant amount is also stored as the intact 108 amino acid precursor peptide proBNP (4). In contrast to proANP, proBNP is only partially stored in granules, and the regulation of BNP synthesis and secretion appears to take place at the level of gene expression (37). The biologically active C-terminal fragment (BNP); the 76 amino acid N-terminal fragment (NT-proBNP); and other high-molecular-weight fragments, possibly intact proBNP 1-108, are each found circulating in human plasma (52-55) (Table 1). The processing of proBNP to NT-proBNP and BNP probably occurs both intracellularly and in the circulation. Figure 2 illustrates the amino acid sequences of proBNP and of the C- and N-terminal fragments, and Table 3 summarizes the characteristics of BNP and NT-proBNP.

In contrast to ANP, BNP is produced both in the atria and in the ventricles in the normal human heart (4,56) (Table 4). Circulating concentrations in healthy subjects are still lower for BNP than for ANP (56,57). In addition to production by atrial and ventricular cardio-

Fig. 2. Simplified schematic drawing showing cleavage of proBNP into biologically active C-ter-minal fragment, BNP, and inactive N-terminal fragment, NT-proBNP. It is likely that the processing of proBNP in vivo is substantially more complex (see text).

Table 3

Characteristics of BNP and NT-proBNP a

Table 3

Characteristics of BNP and NT-proBNP a

Characteristic

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