Intracellular Distribution of Phosphate in the Underfed Rat Developing Weakness and Coma Following Total Parenteral Nutrition

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Abstract
Underfed rats infused intravenously with a glucose-amino acid solution at the rate of 390 kcal/kg/day developed a syndrome of muscular weakness, neuropathy, lethargy and precoma or coma associated with severe hypophosphatemia. The movement of phosphate into the cells was studied to determine where it went and into which organic compounds it was incorporated. All but 8% of the labeled phosphate was found in liver, muscle, bone, and carcass residue. Liver cells took up as much phosphate as bone and twice as much as muscle, on a weight basis. About 90% of the labeled phosphate entering liver was found in the acid-soluble fraction. The specific activity of liver phosphate increased in the infused underfed rats compared to uninfused underfed rats. Infusion of the underfed rat until signs of the syndrome appeared was associated with a 2.7- to 5-fold increase over the correspondingly infused normal rat in the labeling of glucose-6-phosphate, glucose-1-phosphate, and 6-phosphogluconate. No increase over the infused normal rat was observed in most of the other sugar phosphate compounds nor in the non-sugar phosphate compounds such as phospholipids, nucleic acids or proteins. The changes in sugar phosphates observed in the underfed rats probably reflect the enzymatic atrophy associated with underfeeding and the consequent inability to respond to the huge glucose load.