Introduction: Accumulation of 5-oxoproline (pyroglutamic acid) is a rare cause of severe, high anion gap metabolic acidosis in adults. Case: A 21 year old lady presented at 39 weeks gestation in her first pregnancy wi...Introduction: Accumulation of 5-oxoproline (pyroglutamic acid) is a rare cause of severe, high anion gap metabolic acidosis in adults. Case: A 21 year old lady presented at 39 weeks gestation in her first pregnancy with 2 weeks history of shortness of breath. She suffered from ear ache and had been taking Paracetamol on regular basis for a year. She was admitted to having regular alcohol intake until the pregnancy when she stopped. She was not in acute distress and all her observations were stable. The laboratory analysis of renal function was normal. Arterial blood gas showed metabolic acidosis. The anion gap 34 mEq/l which was consistent with metabolic acidosis. Plasma aminoacid screen revealed no abnormality. Chest X-rays showed patchy consolidation keeping with a chest infection. Emergency caesarean section was carried out for fetal distress in first stage of labour. Urine and serum samples were taken which showed an increase in the serum level five Oxoproline to creatinine ratio indicating pyroglutamic metabolic acidosis. Polyglutamate was found in the urine She was admitted to intensive care unit;cardiovascular stable, had no signs of sepsis. She underwent ventilation and haemofiltration. On second day of admission metabolic acidosis was corrected. During the 48 hours treatment with supportive therapy produced general overall improvement. Discussion: Metabolic acidosis that caused by 5-oxoproline results from disruption of the gamma glutamyl cycle. Glutamile synthetase (GS) deficiency is an autosomol recessive disorder. With GS deficiency, reduced glutathione levels increase gamma glutamile synthetase activity, and the resulting gamma—glutamile cystine levels are particularly converted to 5-oxoproline. Intoxication of organic acids is a differential diagnosis of high anion gap metabolic acidosis with no renal impairment, there was no evidence of ethanol, methanol or ethylene glycol ingestion. Suspicion for 5-oxoproline-associated high anion gap metabolic acidosis should be entertained when the cause of high anion gap metabolic acidosis remains poorly defined, the anion gap cannot be explained reasonably by measured organic acids, and there is concomitant acetaminophen use. Conclusion: Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N-acetylcysteine could be beneficial.展开更多
Seven new 4-hydroxyben l-substituted amino acid derivatives (1-7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Go,arodia data Blume. Their structures were determined by s...Seven new 4-hydroxyben l-substituted amino acid derivatives (1-7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Go,arodia data Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1-3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4-7 are the first examples of natural products with the 4-hydroxybenzyl unit linked vici a thioether bond to 2-hydroxy-3mercaptopropanoic acid (4-6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified hi synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher 's method based on the MPA determination rule of A5Rs values. The known compound 4-(hydroxymethy0-5-nifrobenzene1,2-diol (8) exhibited activity against Fe2 r--cysteine induced rat liver microsomal lipid peroxidation with 1050 values of 9.99 x 10 6 mon. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.'s/. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
文摘Introduction: Accumulation of 5-oxoproline (pyroglutamic acid) is a rare cause of severe, high anion gap metabolic acidosis in adults. Case: A 21 year old lady presented at 39 weeks gestation in her first pregnancy with 2 weeks history of shortness of breath. She suffered from ear ache and had been taking Paracetamol on regular basis for a year. She was admitted to having regular alcohol intake until the pregnancy when she stopped. She was not in acute distress and all her observations were stable. The laboratory analysis of renal function was normal. Arterial blood gas showed metabolic acidosis. The anion gap 34 mEq/l which was consistent with metabolic acidosis. Plasma aminoacid screen revealed no abnormality. Chest X-rays showed patchy consolidation keeping with a chest infection. Emergency caesarean section was carried out for fetal distress in first stage of labour. Urine and serum samples were taken which showed an increase in the serum level five Oxoproline to creatinine ratio indicating pyroglutamic metabolic acidosis. Polyglutamate was found in the urine She was admitted to intensive care unit;cardiovascular stable, had no signs of sepsis. She underwent ventilation and haemofiltration. On second day of admission metabolic acidosis was corrected. During the 48 hours treatment with supportive therapy produced general overall improvement. Discussion: Metabolic acidosis that caused by 5-oxoproline results from disruption of the gamma glutamyl cycle. Glutamile synthetase (GS) deficiency is an autosomol recessive disorder. With GS deficiency, reduced glutathione levels increase gamma glutamile synthetase activity, and the resulting gamma—glutamile cystine levels are particularly converted to 5-oxoproline. Intoxication of organic acids is a differential diagnosis of high anion gap metabolic acidosis with no renal impairment, there was no evidence of ethanol, methanol or ethylene glycol ingestion. Suspicion for 5-oxoproline-associated high anion gap metabolic acidosis should be entertained when the cause of high anion gap metabolic acidosis remains poorly defined, the anion gap cannot be explained reasonably by measured organic acids, and there is concomitant acetaminophen use. Conclusion: Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N-acetylcysteine could be beneficial.
基金the National Natural Science Foundation of China (NNSFC Nos. 30825044 and 20932007)+1 种基金the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, No. IRT1007)the National Science and Technology Project of China (Nos. 2012ZX09301002-002 and 2011ZX09307002-01) is acknowledged
文摘Seven new 4-hydroxyben l-substituted amino acid derivatives (1-7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Go,arodia data Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1-3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4-7 are the first examples of natural products with the 4-hydroxybenzyl unit linked vici a thioether bond to 2-hydroxy-3mercaptopropanoic acid (4-6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified hi synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher 's method based on the MPA determination rule of A5Rs values. The known compound 4-(hydroxymethy0-5-nifrobenzene1,2-diol (8) exhibited activity against Fe2 r--cysteine induced rat liver microsomal lipid peroxidation with 1050 values of 9.99 x 10 6 mon. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.'s/. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).