Specific regulation of intestinal nutrient transporters by their dietary substrates

Most intestinal nutrient transporters studied to date are regulated by dietary levels of their substrates. With increasing substrate levels, transporters for glucose, fructose, two classes of nonessential amino acids, and peptide are up-regulated; transporters for trace minerals and for some vitamins (perhaps mainly those with little passive uptake) are down-regulated; transporters for essential AAs exhibit minimal activity at intermediate substrate levels. Compared to bacterial proteins, intestinal transporters show modest peak-to-base activity ratios (< 10) and slow responses (hours or days) in their regulation. The regulatory signals are in only some cases transported substrates. Regulation of numerous transporters involves changes in transporter number. Since the intestine's absorptive capacities are (contrary to widespread belief) closely matched to dietary intakes, the function of regulation is to provide just enough absorptive capacity, without wasting biosynthetic energy on unneeded transporters. This area of research has exploded recently and is full of important unsolved problems. Regulatory patterns remain unknown for most basolateral transporters, bile acids, short-chain fatty acids, and numerous trace minerals and vitamins. Regulatory patterns for multiple transporters of the same nutrient (e.g. multiple transporters for glucose or for neutral AAs) are only beginning to be resolved. Why the regulatory signals are so often seemingly 'inappropriate' remains unknown. As yet, there has been no detailed study of intestinal transporter regulation at the molecular level. The possibility that activities of some transporters are irreversibly fixed at the crypt-cell state by the prevailing substrate levels remains to be tested. We anticipate that intestinal nutrient transporters, which among the eukaryotic enzymes are most directly exposed to a changing environment, will furnish suitable material for studying many questions of regulatory biology.