Carnosinase activity of human gastrointestinal mucosa.

Abstract

SUMMARY Carnosinase, the dipeptidase which hydrolyses carnosine and other histidine-containing dipeptides, was assayed in mucosal tissues of the human and of the rat gut. Kinetic properties of the intestinal enzyme were found to be similar to carnosinase of other animal tissues. Little or no activity was detected in human gastric or colonic mucosa, and the levels were lower in duodenal than jejunal mucosa. The distribution of carnosinase is similar to that of the disaccharidases. Mean carnosinase activity was 8'8 units/g weight in 15 patients with histologically normal mucosa compared with 5-7 units in five with villous atrophy. The enzyme levels increased with histological improvement of the mucosa in patients with coeliac disease on a gluten-free diet. Tolerance curves for carnosine and its constitutent amino acids showed malabsorption of the dipeptide in a patient with carnosinase deficiency. It is concluded that the intestinal mucosa has much less hydrolase activity for carnosine than for glycylglycine and other dipeptidases, and the relatively slow hydrolysis appears to be the rate-limiting step in the total absorptive process.

Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells

“…Zucker obese rats treated with L-carnosine were less dyslipidemic and exhibited improved renal function in comparison with the control group (Aldini et al, 2011). Unfortunately, such dietary supplementation in human is ineffective due to the presence of L-carnosinase in human gastrointestinal mucosa and other tissues that degrade this dipeptide (Sadikali et al, 1975;Teufel et al, 2003). Studies using N-acetyl cysteine have proven that the strategy of designing and synthesizing pharmaceuticals with better scavenging activity might be feasible (Lasram et al, 2015).…”

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

“…The presence of such effective carnosinase activity in plasma explains why Asatoor et al (1970) and Sadikali et at. (1975) failed to detect carnosine in plasma after carnosine ingestion by humans.…”

“…A putative proton-linked peptide carrier has also recently been partially characterized in basolateral membranes, and carnosine inhibited the transport of glycyl-L-proline by it (Dyer, Beechey, Gorvel, Smith, Wootton & CARNOSINE ABSORPTION AND EXCRETION Shirazi-Beechey, 1990). However, carnosinase activity has been identified in the small intestine of several species including humans (Parshin, 1946;Sadikali, Darwish & Watson, 1975) though Parshin (1946) found less activity in human mucosa than in other species, and Hanson & Smith (1949) reported that it was absent from pig intestine though present in pig kidney.…”

“…Sadikali et al (1975) concluded that intestinal hydrolysis of carnosine was the rate-limiting step in carnosine absorption. This conclusion was based mainly on the observation that a patient with a deficiency of intestinal carnosinase produced a relatively low serum histidine tolerance curve after ingestion of carnosine.…”

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

“…This is an H + -driven process. Inside the enterocytes, a limited amount of carnosine is hydrolyzed by carnosinase-2 into β-alanine and histidine (Sadikali et al 1975). The intracellular carnosine is exported by peptide/histidine transporters 1 and 2 (PHT1 and PHT2) out of the enterocyte across its basolateral membrane into the lamina propria of the small-intestinal mucosa.…”