Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 microM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 microM) and alanine + phenylacetate (79, 13-467 microM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first-order kinetics with t1/2S of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance. 309 49

A twenty year old female was referred to hospital by her GP, after he received the results of blood tests taken earlier in the day. She had presented to him complaining of malaise, nausea and anorexia over a 3 day period. On the day of referral she had also become jaundiced with dark urine, but normal stool colour. There was no abdominal pain. She had no significant past medical history with no history of jaundice, liver disease or autoimmune conditions, and no apparent risk factors for blood-borne hepatitis infection. There was no relevant family history. She was taking no prescribed medication, had not taken any over the counter medication or herbal remedies. She denied excessive alcohol use or use of intravenous drugs in the past, although she was not specifically questioned on the use of other recreational drugs. She was a single mother and admitted to being under considerable stress recently. On examination she appeared well, apart from marked jaundice. There were no signs of hepatic encephalopathy or chronic liver disease. Abdominal examination revealed mild left upper quadrant tenderness, but no significant hepatomegaly. Liver function tests (LFTs) taken by her GP are shown in Table 1, revealing marked elevation of the Alanine Transaminase (ALT) (Table 1), with a relatively preserved albumin. Unfortunately her International Normalised Ratio (INR) had not been measured. An Ultrasound of the abdomen demonstrated a normal size liver with normal contour and texture with no other abnormality.
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PMID:Ecstasy: an important cause of acute liver failure. 2161 22