Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supplement of the deficient neurotransmitters is one of the most effective therapies for neurodegenerative disorders. For the treatment of Parkinson's disease, L-DOPA therapy has been applied to replace dopamine, and droxidopa (L-threo-3,4-dihydroxyphenylserine) therapy to supply noradrenaline (NA). Droxidopa, an artificial amino acid, is decarboxylated by aromatic L-amino acid decarboxylase (AADC) into NA. By application for Parkinson's disease, it alleviated neurological symptoms such as freezing phenomenon, which are refractory to L-DOPA. However, as a precursor of a monoamine, droxidopa was found to be not so effective as L-DOPA; and the clinical efficiency of droxidopa is variable among patients. The metabolic pathway of droxidopa in the brain was examined using human materials. The intraventricular fluid of patients treated with droxidopa, and of control was analyzed by high-performance liquid chromatography with multi-eletrochemical detection (Neurochem). In the intraventricular fluid of the patients treated, free NA concentration increased to be 5.67 +/- 3.40 nM from non-detectable level in the control patients. The patients with higher free NA levels clinically responded better to droxidopa. However, free NA levels varied among patients; and the mechanism of the individual variance should be clarified. In the intraventricular fluid, in addition to NA, a large amount of a metabolite of droxidopa by catechol-O-methyltransferase (COMT), 3-O-methoxy-droxidopa (3OMD), was detected, followed by the metabolites by DOPS-aldolase (DOPS-ALD), protocatechualdehyde and protocatechuic acid. It indicates that considerable parts of administered droxidopa are catabolized by COMT and DOPS-ALD, but not by AADC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study on the metabolism of droxidopa in humans]. 783 60

We examined the kinetics study of serum enzyme after the administration of beta-blocking agents or alpha-stimulator in the experimental rats. Following the administration of beta-blocking agents, propranolol and pindolol, the serum levels of adenylate kinase, aldolase, lactate dehydrogenase and aspartate aminotransferase as well as that of creatine kinase increased in rats. The same was observed following the administration of noradrenaline (an alpha-stimulator). Isoenzyme pattern indicated that most of these enzymes were considered to be released from muscular tissues. There were also changes in serum calcium, inorganic phosphorus and magnesium, concurrently with the release of the enzymes into the serum.
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PMID:Effects of beta-blocking agents on the release of various enzymes in muscular tissues. 796 81

The monoamines and their metabolites were analyzed in the intraventricular fluid of parkinsonian patients treated with L-DOPA alone or together with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), the precursor amino acids of dopamine and noradrenaline, respectively. In the intraventricular fluid of the patients administered with L-DOPA, the level of dopamine metabolites were higher than control, suggesting enhanced turnover of dopamine in the brain. However, L-DOPA administration increased free noradrenaline only slightly, and did not affect serotonin and its metabolite. On the other hand, by administration of L-DOPA combined with L-threo-DOPS, the levels of monoamines increased in general, whereas the monoamine metabolites by catechol-O-methyltransferase were reduced compared with those in the patients treated with L-DOPA alone. Only a minor part of L-threo-DOPS was metabolized into noradrenaline by aromatic L-amino acid decarboxylase, and it was metabolized mainly by two other enzymes, catechol-O-methyltransferase and DOPS-aldolase in the brain. An overview of the metabolism of neurotransmitters in the brain proved to be useful to evaluate the therapeutic effects of these precursor amino acids.
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PMID:The metabolism of L-DOPA and L-threo-3,4-dihydroxyphenylserine and their effects on monoamines in the human brain: analysis of the intraventricular fluid from parkinsonian patients. 883 86

A 72-year-old woman with von Recklinghausen's disease was referred to our hospital because of pain and muscle weakness in her thighs. She had elevated serum values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a diagnosis of polymyositis was made. Treatment with prednisolone improved muscle strength, and laboratory values returned to normal. Computed tomography, magnetic resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left adrenal gland. Endocrinologic investigation disclosed elevation of serum and urine catecholamines. Since the blood pressure was normal, nonfunctioning pheochromocytoma was diagnosed clinically. The nonhypertensive course was attributed to reduced vascular response to noradrenaline. Serum lactate dehydrogenase. alkaline phosphatase. and asparate aminotransferase became elevated, and abdominal computed tomography showed a well-defined mass measuring 13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of elongated spindle-shaped atypical cells arranged in intersecting bundles. Immunohistochemically, the cells of this tumor were reactive for alpha-smooth muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the liver. Eight months after onset of symptom, the patient developed hepatic coma and died. The mean age at presentation with pheochromocytoma in von Recklinghausen's disease patients age is 42 years. Our patient was considerably older. To the best of our knowledge this is the first report of a patient with von Recklinghausen's disease developing polymyositis. asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to remain aware of the possibility of cancer in von Recklinghausen's disease.
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PMID:[A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma]. 1523 55