Pediat. Res. 4: 89-95 (1970) ExtractPipecolic acid has been found in urine from normal infants and from children with hyperlysinemia. The reaction of pipecolic acid with ninhydrin reagent, using separation procedures in automated ion-exchange systems for amino acid analysis, produced a color constant of low value (1.21 compared with 27.6 for leucine) that could be overlooked in routine analyses of physiological fluids. Pipecolic acid was present in the urine from: four premature infants (6-23 days old) 1.2-8.1 ,«g/ m g creatinine; two of four term infants (3-5 days old) 1.3 and 2.1 ,«g/mg creatinine; and one of four infants (4-11 months old) 2.1 /jg/mg. No pipecolic acid was found in the urines of four infants 14-30 months old. In patients with hyperlysinemia, the amounts of pipecolic acid excreted in the urine were: 3.1 ^g/mg creatinine (4-year-old girl); 5.2 //g/rng creatinine (6-year-old boy); 6.2 /"g/mg creatinine (9-year-old girl); and 4.8 ,ug/mg creatinine (12-year-old girl). SpeculationThe low color yield of pipecolic acid, when separated by standard automated ion-exchange analysis methods, may account for past failures to detect small amounts of this substance in physiological fluids. Amounts of pipecolic acid excreted by young infants and by children with hyperlysinemia indicate that a degradation pathway for lysine, via pipecolic acid to a-aminoadipic acid, is operative in man. Introductionamino acids by infants, children, and adults [2,4,8-10, 14, 16, 19, 21-23, 25, 26, 28, 30, 36, 39, 41-45, 47, 48] Pipecolic acid has been shown to be a product of lysine make no mention of pipecolic acid as a normal urinary metabolism in rats [31][32][33], guinea pigs [5,20,34], constituent, but JAGENBURG [18] detected pipecolic and turkeys [6,7]. It has been detected in plants [53] acid in urine from infants less than 1 year old; however, and is derived from lysine in some of them [15,24]. he was unable to find it in urine of adults. Pipecolic Certain microorganisms form pipecolic acid from a-acid also has been found in the urine of a child with aminoadipic acid [3]; others derive it from lysine by hyperlysinemia [49] and in urine of patients with pathways similar to those described for mammals [20, hyperthyroidism [38]. GHADIMI et al. [13], however,35].attempting to detect pipecolic acid in urine from norReports of the presence of pipecolic acid in human mal premature infants, infants, and adults, and from urine are conflicting. Numerous studies of excretion of patients with hyperlysinemia were unsuccessful, and

ExtractThree children with familial hyperlysinemia were found to excrete, respectively, 1,934 nmol/24 hr, 730 nmol/24 hr, and 1,121 nmol/24 hr hypusine and 16.1 mmol/24 hr, 7.0 mmol/24 hr, and 16.6 mmol/24 hr lysine. Ten juvenile control subjects excreted 35-253 nmol/24 hr (mean 156 nmol/24 hr) hypusine and 0.2-1.5 mmol/24 hr (mean 0.7 mmol/24 hr) lysine. Three infant control subjects were found to excrete 156 nmol/24 hr, 60 nmol/24 hr, and 77 nmol/24 hr hypusine. Serum levels of hypusine for subjects with hyperlysinemia were normal (less than 20 nmol/100 ml). SpeculationPatients with familial hyperlysinemia excrete both hypusine and lysine at levels 7-10 times higher than those observed for control subjects, while serum levels of hypusine in patients with hyperlysinemia are not elevated. These findings suggest that hypusine may be an endometabolite of lysine and not further metabolized or utilized.

Normal children and children with familial hyperlysinemia were given L-(U-14 C)-lysine by intramuscular injection. Labeled pipecolic acid and A'-a-acetyllysine were found in the urines, indicating derivation of these substances from lysine. The percentage of administered radioactivity excreted as 14 CO 2 and as urinary lysine varied markedly between controls and those with hyperlysinemia, but the percentage excreted in the urine in the form of various metabolites of lysine was about the same for controls (1.7-2.4) and those with hyperlysinemia (1.9-2.2). The proportion of these urinary lysine metabolites comprising pipecolic acid, homocitrulline, homoarginine, iV-e-acetyllysine and jV-a-acetyllysine was two to seven times greater for children with hyperlysinemia than for controls. These findings suggest that these pathways for lysine degradation are being maximally utilized by patients with familial hyperlysinemia who cannot degrade lysine by way of the saccharopine pathway. Speculation