Impairment of induction of delta-aminolevulinic acid synthase by gluconeogenic amino acids and carbohydrates in vitro.
This study was undertaken in a system of chick embryo liver cells incubated in Earle's Basal Salt Solution with hormones. Impairment of induction of delta-aminolevulinic acid synthase (ALAS) by allyl-isopropylacetamide (AIA) was observed in the presence of glucose. Fructose and various gluconeogenic substances including gluconeogenic amino acids had a similar effect. Leucine, which is purely ketogenic, did not influence induction of ALAS. SH-containing amino acids increased induction of ALAS by AIA. The glucose analogues 3-O-methylglucose and 2-deoxyglucose did not impair induction of ALAS by AIA. The inhibitory effect of glycerol, fructose, and glycine was not affected by 3-O-methylglucose but was reversed by 2-deoxyglucose. The results indicate that the salutary effects of proteins on acute attacks of hepatic porphyria are probably caused by their gluconeogenic properties and that glucose-6-phosphate, or metabolite of glucose-6-phosphate that is not in the glycolytic pathway, is the active agent that leads to the glucose-like effect.
D019325:3-O-Methylglucose; D000624:5-Aminolevulinate Synthetase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000502:Allylisopropylacetamide / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000603:Amino Acids, Sulfur / Q000494:pharmacology; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology*; D002642:Chick Embryo; D003847:Deoxyglucose / Q000494:pharmacology; D003997:Dicarbethoxydihydrocollidine / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005632:Fructose / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008757:Methylglucosides / Q000494:pharmacology; D011166:Porphyrins / Q000378:metabolism; D014306:Trioses / Q000494:pharmacology
D000596:Amino Acids; D000603:Amino Acids, Sulfur; D002241:Carbohydrates; D008757:Methylglucosides; D011166:Porphyrins; D014306:Trioses; D019325:3-O-Methylglucose; D000502:Allylisopropylacetamide; D005632:Fructose; D003997:Dicarbethoxydihydrocollidine; D003847:Deoxyglucose; D000624:5-Aminolevulinate Synthetase; D005947:Glucose