Bacterial phenylalanine and phenylacetate catabolic pathway revealed

Aromatic compounds constitute the second most abundant class of organic substrates and environmental pollutants, a substantial part of which (e.g., phenylalanine or styrene) is metabolized by bacteria via phenylacetate. Surprisingly, the bacterial catabolism of phenylalanine and phenylacetate remained an unsolved problem. Although a phenylacetate metabolic gene cluster had been identified, the underlying biochemistry remained largely unknown. Here we elucidate the catabolic pathway functioning in 16% of all bacteria whose genome has been sequenced, including Escherichia coli and Pseudomonas putida. This strategy is exceptional in several aspects. Intermediates are processed as CoA thioesters, and the aromatic ring of phenylacetyl-CoA becomes activated to a ring 1,2-epoxide by a distinct multicomponent oxygenase. The reactive nonaromatic epoxide is isomerized to a seven-member O-heterocyclic enol ether, an oxepin. This isomerization is followed by hydrolytic ring cleavage and β-oxidation steps, leading to acetyl-CoA and succinyl-CoA. This widespread paradigm differs significantly from the established chemistry of aerobic aromatic catabolism, thus widening our view of how organisms exploit such inert substrates. It provides insight into the natural remediation of man-made environmental contaminants such as styrene. Furthermore, this pathway occurs in various pathogens, where its reactive early intermediates may contribute to virulence.     

Ornithine transcarbamylase deficiency in pregnancy

Summary Women heterozygous for mutations at the ornithine transcarbamylase (OTC) locus may be at risk for hyperammonaemia and its untoward effects including coma and death in the postpartum period. We present the case of a pregnant woman heterozygous for OTC deficiency (McKusick 311250) whose past medical history was significant for two prior pregnancies complicated by postpartum hyperammonaemic coma. In the index pregnancy, increased levels of serum ammonium were noted during labour. Postpartum hyperammonaemia was averted by administration of oral sodium benzoate. Our experience demonstrates that in women at risk, perilous hyperammonaemia can be prevented through appropriate medical management. An erratum to this article is availale at .     

Ornithine decarboxylase in perfused rat heart

In the isolated perfused rat hearts, the activity of tissue ornithine decarboxylase gradually decreases over 90 min. In contrast, the activity of S-adenosylmethionine decarboxylase, lactate dehydrogenase, and glutamate-oxalacetate transaminase stays unchanged after a small decrease during the first 10 min. Ornithine decarboxylase is released from the perfused heart under conditions in which neither the lower molecular weight S-adenosylmethionine decarboxylase nor polyamines leak out. Ten minutes of ischaemia did not change the rate of release of ornithine decarboxylase. Ischaemia followed by reperfusion (20 min) increased release of ornithine decarboxylase.     

门冬氨酸鸟氨酸对肝纤维化大鼠的实验研究

目的通过大鼠肝纤维化动物模型，研究门冬氨酸鸟氨酸防止肝纤维化的作用。方法采用0．03％的硫代乙酰胺溶液腹腔注射制备大鼠肝纤维化模型，观察门冬氨酸鸟氨酸对大鼠肝功能指标、组织病理学改变和脯氨酸羟化酶表达的影响。结果门冬氨酸鸟氨酸能降低大鼠AST，ALT水平（P〈0．05），减轻肝纤维化的病理改变进程。结论门冬氨酸鸟氨酸具有一定的抗肝纤维化作用。     

Ornithine decarboxylase gene is overexpressed in colorectal carcinoma

AIM: To investigate the ornithine decarboxylase (ODC) gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology. METHODS: Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR. ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay. RESULTS: A cell line, which could steadily secrete anti-ODC mAb, was selected through subcloning four times. Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P<0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6±1.03% vs5.26±5%,P<0.01). CONCLUSION: ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.     

Ornithine transcarbamylase deficiency unmasked because of gastrointestinal bleeding

Ornithine transcarbamylase (OTC) is a mitochondrial-matrix enzyme that catalyzes conversion of ornithine and carbamyl phosphate to citrulline, the second step in the urea cycle. The urea cycle is the most important pathway to detoxification of ammonia in human beings. Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, inherited as an X-linked disorder that can cause fatal hyperammonemia in male newborns. Women with OTCD have a variable expression of their disease, the variability being determined by lyonization (random inactivation) of the X chromosome. We report a case of a 28-year-old woman who presented with hyperammonemic encephalopathy that was precipitated by a gastrointestinal bleed unmasking OTCD.     

Ornithine transcarbamylase deficiency: adult onset of severe symptoms

Deficiency of ornithine transcarbamylase, an enzyme in the urea cycle, results in hyperammonemia. The X-linked recessive inheritance results in neonatal death of affected males but a variable symptomatic pattern in females, with onset of symptoms in childhood. We report the cases of two heterozygous women with onset of severe symptoms (encephalopathy and focal neurologic deficits) in adulthood.     

Glycolysis revisited

Summary Glycolysis is usually considered as a paradigm metabolic pathway, due to the fact that it is present in most organisms, and also because it is the pathway by which an important nutrient, glucose, is consumed. Far from being completely understood, the regulation of this pathway witnessed several important progresses during the last few years. One of these is the discovery of fructose 2,6-bisphosphate, a potent stimulator of phosphofructokinase and inhibitor of fructose-1,6-bisphosphatase. Originally found in the liver during the course of a study on the mechanism by which glucagon acts on gluconeogenesis, this compound is now recognized as a major element in the control of glycolysis and/or gluconeogenesis in many cell types and in various organisms. The other finding is that of a regulatory protein that modulates the activity of glucokinase, the enzyme that phosphorylates glucose in the liver and in the beta cells of pancreatic islets.Presented as the Minkowski Lecture, EASD Meeting Prague, Czechoslovakia 1992     

Trimethoprim-sulfamethoxazole revisited

During the past 3 decades, the combination of trimethoprim and sulfamethoxazole has occupied a central role in the treatment of various commonly encountered infections and has also been particularly useful for several specific clinical conditions. However, changing resistance patterns and the introduction of newer broad-spectrum antibiotics have led to the need to carefully redefine the appropriate use of this agent in clinical practice. While trimethoprim-sulfamethoxazole's traditional role as empirical therapy for several infections has been modified by increasing resistance, it remains a highly useful alternative to the new generation of expanded-spectrum agents if resistance patterns and other clinical variables are carefully considered. It also seems to have an increasing role as a cost-effective pathogen-directed therapy with the potential to decrease or delay development of resistance to newer antibiotics used for empirical treatment. In addition, trimethoprim-sulfamethoxazole continues to be the drug of choice for several clinical indications.     

Pre-excitation revisited

Epicardial excitation mapping and the introduction of electrical stimulation of the heart have brought new techniques to the study of pre-excitation. The concept of three anomalous atrioventricular connections (Kent bundle, James bundle and Mahaim fibers) seems at present to be the most attractive means of explaining different electrocardiographic patterns found in this syndrome. The possible pathways and the mode of initiation of the frequently found tachycardias in such cases are outlined. An evaluation of our current knowledge on the pre-excitation syndrome confronts us with the many gaps in our knowledge of electrophysiology of the human heart.     

Haemochromatosis revisited

Haemochromatosis is a genetic disease caused by hepcidin deficiency, responsible for an increase in intestinal iron absorption. Haemochromatosis is associated with homozygosity for the HFE p.Cys282Tyr mutation. However, rare cases of haemochromatosis (non-HFE haemochromatosis) can also be caused by pathogenic variants in other genes (such as HJV, HAMP, TFR2 and SLC40A1). A working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society) has concluded that the classification based in different molecular subtypes is difficult to be adopted in clinical practice and has proposed a new classification approaching clinical questions and molecular complexity. The aim of the present review is to provide an update on classification, pathophysiology and therapeutic recommendations.