Folate malabsorption in aged rats related to low levels of pancreatic folyl conjugase

Abstract

Folate absorption and transport were studied in young (2 to 3 months) and aged (28 to 30 months) rats. From studies of the rise in serum folate levels after ingestion and transport across everted intestinal segments it was concluded that the absorption of dietary polyglutamyl folates was impaired in aged animals. Simple folates (monoglutamyl pteroates) were utilized equally well in both age groups. Decreased hydrolysis of polyglutamylfolates to simple forms have been observed in the aged group. High folyl conjugase (pteroyl gamma-glutamyl hydrolase) levels are induced in pancreas as a response to dietary folate intake; the conjugase is secreted into the gut lumen where enzyme levels rise sequentially reaching maximum in the midgut region within 30 to 60 min after folate ingestion. The rise in serum folate after folate ingestion parallels the rise in luminal folyl conjugase. Pancreatic and luminal conjugases (but not mucosal conjugase) have similar pH optima. It is suggested that dietary folates are preferentially hydrolyzed to absorbable forms by a luminal folyl conjugase which is of pancreatic origin. The overall enzyme levels are much lower in pancreas of the aged rats, leading to reduced availability of absorbable dietary folates and resulting in folate malabsorption in these animals. It is suggested that the intestinal mucosal conjugase does not play a significant role in the physiological absorption of dietary folates.