The glomerular sieving of pepsinogen A and C in man

Abstract

Pepsinogen A (PGA) and pepsinogen C (PGC) are negatively charged, low molecular weight (LMW) proteins with a striking difference in renal handling: PGA (molecular weight 43,500 daltons) shows a high fractional excretion while the fractional excretion of PGC (molecular weight 40,500 daltons) is low, presumably due to tubular reabsorption. As these data suggest a high glomerular sieving of pepsinogens, we assessed the glomerular sieving coefficient (GSC) of PGA, PGC and several other proteins from their renal extractions. For this purpose blood samples were obtained simultaneously from the aorta (A) and right renal vein (V) in nine patients undergoing an elective heart catheterization. After correction of A-V differences for diuresis with the A-V difference of transferrin, GSCs (+/- SEM) for PGA and PGC were 0.90 +/- 0.14 and 0.85 +/- 0.17, respectively, GSC of beta 2-microglobulin being 0.90 +/- 0.12. For albumin and IgG, known to have a low GSC, low values were found. It is concluded that the GSC of a LMW protein in man can be calculated from both its A-V difference over the kidney and the A-V difference of an inert marker with a GSC of 1, provided they are corrected by the A-V difference of an inert marker with a GSC of 0. Our results demonstrate that PGA and PGC are almost freely filtered through the glomerular basement membrane despite their size and negative net molecular charge.

Serum concentrations of pepsinogen A in healthy dogs after food deprivation and after feeding

“…Another possibility is species-specific differences in the metabolism of PG. Studies 2,16 in humans documented that despite a negative net charge and a molecular mass of 42 kd, human PG A is almost freely filtered through the glomerular basement membrane; therefore, human PG A is found in urine at concentrations 10 to 100 times higher than concentrations in serum. In addition, PG A is partially metabolized by the kidneys.…”

Identification of Novel Cryptic Multifunctional Antimicrobial Peptides from the Human Stomach Enabled by a Computational–Experimental Platform

“…These findings could also help explain an intriguing peculiarity of pepsinogen physiology. It has long been known that a small but not negligible amount of pepsinogen is secreted in the bloodstream, filtered by the kidneys, and released unchanged in the urine . This pepsinogen fraction, also known as “uropepsinogen”, when purified from urine and exposed to pH 2.0, undergoes autocatalytic processing to fully active pepsin. , However, under physiological conditions, autocatalytic activation in the urine is highly unlikely.…”