A new theory of enterorecirculation of amino acids and its use for depleting unwanted amino acids using oral enzyme-artificial cells, as in removing phenylalanine in phenylketonuria.
Oral binders remove intestinal bile acid and prevent its reabsorption and recycling thereby lowering systemic cholesterol levels. The results in this paper demonstrate the presence of another extensive enterorecirculation for amino acids. Pancreatic and other glandular secretions into the intestine contain large amounts of proteins, enzymes and polypeptides. Tryptic digestion converts these into amino acids which are then reabsorbed back into the body as they pass down the intestine. This paper shows that this forms a large enterorecirculation of amino acids between the body and intestine. The dietary protein source of amino acids is negligible when compared to the endogenous source, since this paper shows that protein-free diet did not alter the intestinal amino acid concentration. This raises the possibility of using this for the selective depletion of specific body amino acids. In this paper we use a phenylketonuria (PKU) model in rats to test the use of this hypothesis. In PKU rats, artificial cells microencapsulated phenylalanine ammonia lyase (PAL) given orally is more effective than a phenylalanine-free diet. The enzyme artificial cells are more efficient in lowering PHE in the intestine, plasma and cerebrospinal fluid. Compared to PKU on PHE-free diet, this has resulted in better weight gain and general physical condition. Preliminary studies also show that artificial cells microencapsulated asparaginase, glutaminase and tyrosinase given orally can deplete the corresponding amino acid from the intestine.
Chang
T M
TM
Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Bourget
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Lister
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D000596:Amino Acids / Q000032:analysis / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D004304:Dosage Forms; D004339:Drug Compounding; D007413:Intestinal Mucosa / Q000378:metabolism*; D007419:Intestinal Secretions / Q000737:chemistry / Q000378:metabolism*; D007422:Intestines / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D010649:Phenylalanine / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010650:Phenylalanine Ammonia-Lyase / Q000627:therapeutic use*; D010661:Phenylketonurias / Q000139:chemically induced / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000596:Amino Acids; D004304:Dosage Forms; D010649:Phenylalanine; D010650:Phenylalanine Ammonia-Lyase