Accumulation of lysine dipeptides in the brain in hyperpipecolatemia

Gatfield, P. D.; Taller, E.

doi:10.1016/0006-8993(71)90432-x

Cited by 14 publications

(3 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two defects of the pipecolic acid pathway are known. They are the hyperlysinaemia with periodic hyperammonaemia probably caused by a defect of the lysine oxidoreductase [16,17] and a hyperpipecolataemia in which the metabolic defect is unknown [13,19].…”

Section: Introductionmentioning

confidence: 99%

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Przyrembel¹,

Bachmann²,

Lombeck³

et al. 1975

Clinica Chimica Acta

View full text Add to dashboard Cite

SummaryInvestigation of a psychomotodcally retardcd girl showed excretion of abnormal amounts of alpha-ketoadipic acid, alpha-hydroxyadipic acid, alphaaminoadipic acid, 1,2-butenedicarboxylic acid and elevation of plasma alphaaminoadipic acid levels. T}-e identity of these metabolites was established by various methods. The excretion oi alpha-aminoadipic acid correlated to the lysine intake. Degradation studies with cultured fibroblasts indicate a defect in the oxidative decarboxyla:ion of alpha-ketoadipic acid (see Clin. Chim. Acta, 58 (1975) 271).

show abstract

Section: Introductionmentioning

confidence: 99%

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Przyrembel¹,

Bachmann²,

Lombeck³

et al. 1975

Clinica Chimica Acta

View full text Add to dashboard Cite

show abstract

“…We can, therefore, assume that in the adult mouse most pipecolic acid is leaving the brain unaltered and only a small amount is metabolized [Nishio et al, 19811. With regard to the developmental period, Nishio et al [1982b] have found that access of pipecolic acid to the brain is easier in the newborn mouse than in the adult and that this compound is actively metabolized in the newborn animal. This difference between neonate and adult could help us to explain the high levels of pipecolic acid found in brain, serum, and urine that have been associated with severe mental retardation and extensive degeneration of the CNS in infants [Gatfield and Taller, 1971 ;Thomas et al, 19751. In conclusion, our present results, together with our previous findings [Schmidt-Glenewinkel et al, 1977;Nomura et al, 1978;Nishio et al, 19811 do not support the view of other authors [KasC et al, 1967[KasC et al, , 1974Stepita-Klauco and Dolezalova, 19741 on a brain endogenous synthesis of piperidine and cadaverine. The hypothesis of a brain metabolic activity for piperidine seems also to be questioned by our findings.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of cadaverine and pipecolic acid in brain and other organs of the mouse

Nomura

Schmidt-Glenewinkel

Giacobini

et al. 1983

J of Neuroscience Research

View full text Add to dashboard Cite

Cadaverine and pipecolic acid metabolism was investigated in vitro in several organs of the mouse by measuring 14CO2 formation from labeled precursors. The liver showed the highest formation of 14CO2 from [1,5-14C]-cadaverine, whereas brain demonstrated a much lower formation. Anaerobiosis or inhibition of monoamineoxidase (MAO) activity significantly reduced 14CO2 formation in every organ, but inhibition of diamine oxidase (DAO) activity had no effect in brain and kidney. Piperidine was formed from cadaverine in vitro only in the large intestine and its content. This formation is probably of bacterial origin. Under a variety of experimental conditions we were unable to demonstrate any formation of piperidine in brain from cadaverine. Biosynthesis in vitro of [3H]-piperidine from D,L-[3H]-pipecolic acid was very low in brain and kidney. With the exception of brain and kidney, no other organs showed any formation of [3H]-piperidine. Neither MAO nor DAO inhibition influenced [3H]-piperidine formation in the large intestine with its content. Following 1 hr incubation at 37 degrees C under aerobic conditions, the levels of [14C]-pipecolic acid and [3H]-piperidine recovered from mouse brain homogenate did not indicate any significant degradation of these two substances. Our results suggest that under in vitro conditions, cadaverine is not a precursor of piperidine in brain, liver, heart, and kidney and that only very low levels of piperidine can be formed from pipecolic acid in brain. Outside the brain, formation of piperidine from pipecolic acid is detectable only in kidney and in the content of the large intestine. The latter is probably of bacterial origin. Our results do not support previous findings from other authors on an endogenous origin of piperidine in brain from cadaverine and pipecolic acid, and they suggest that a) cadaverine is not a precursor of piperidine in brain, b) the conversion of pipecolic acid into piperidine in the brain does not constitute a major metabolic pathway, and c) the main source of piperidine in the CNS may be of nonneural origin.

show abstract

“…The authors proposed that the increased levels of serum pipecolic acid resulted from an inherited inborn error of lysine metabolism. The metabolic abnormality was believed to have had a causative relation-ship with the severe clinical problems which resulted in death at 2 % years of age (Gatfield et al 1968, Gatfield & Taller 1971.…”

mentioning

confidence: 99%

Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease

et al. 1975

View full text Add to dashboard Cite

A male infant with hyperpipecolic acidemia is described. To our knowledge this is only the second report of this disorder. As with the previous case, our patient's course was characterized by persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones and diminished visual acuity associated with nystagmus, abnormal discs and retinal changes. Death occurred at 2 years of age, following a progressive loss of neurological function.Pipecolic acid was repeatedly present in the serum at a concentration of 4-5 mg %. Trace amounts of this compound were also detected in the urine.In addition, an adaption of the method of Piez et al. (1956) for the direct quantitation of pipecolic acid in serum was evaluated and found to be very useful for the biochemical diagnosis of this disorder.

show abstract

Accumulation of lysine dipeptides in the brain in hyperpipecolatemia

Cited by 14 publications

References 4 publications

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Metabolism of cadaverine and pipecolic acid in brain and other organs of the mouse

Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease

Contact Info

Product

Resources

About