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B Wermuth

Publications and source records attributed to B Wermuth.

87 records · Page 5Linked to original sources
PubMed1980

Multiple aldehyde reductases of human brain.

Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC 1.1.1.2. The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme ("SSA reductase") differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of gamma-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles.

Aldehyde Oxidoreductases↗
PubMed1980

Human brain aldehyde reductases: relationship to succinic semialdehyde reductase and aldose reductase.

Human brain contains multiple forms of aldehyde-reducing enzymes. One major form (AR3), as previously shown, has properties that indicate its identity with NADPH-dependent aldehyde reductase isolated from brain and other organs of various species; i.e., low molecular weight, use of NADPH as the preferred cofactor, and sensitivity to inhibition by barbiturates. A second form of aldehyde reductase ("SSA reductase") specifically reduces succinic semialdehyde (SSA) to produce gamma-hydroxybutyrate. This enzyme form has a higher molecular weight than AR3, and uses NADH as well as NADPH as cofactor. SSA reductase was not inhibited by pyrazole, oxalate, or barbiturates, and the only effective inhibitor found was the flavonoid quercetine. Although AR3 can also reduce SSA, the relative specificity of SSA reductase may enhance its in vivo role. A third form of human brain aldehyde reductase, AR2, appears to be comparable to aldose reductases characterized in several species, on the basis of its activity pattern with various sugar aldehydes and its response to characteristic inhibitors and activators, as well as kinetic parameters. This enzyme is also the most active in reducing the aldehyde derivatives of biogenic amines. These studies suggest that the various forms of human brain aldehyde reductases may have specific physiological functions.

Alcohol Oxidoreductases↗
PubMed1979

Amidination of amino groups of aldehyde reductase from human liver.

Amidination of human liver aldehyde reductase (alcohol:NADP+ oxidoreductase, EC 1.1.1.2) with monofunctional n-alkane methylimidates increased the enzymic activity by 10--30%, whereas analogous bifunctional imidoesters caused a loss of activity of about 80%. Both effects were prevented in the presence of the coenzyme NADPH or NADP+, but not of the substrate 4-nitrobenzaldehyde. Amidination increased the apparent Michaelis constant of both the coenzyme (up to 20-fold) and the substrate (about 5-fold). Bifunctional imidoesters with at least 4 carbon atoms between the functional groups (approx. 0.7 nm) crosslinked the enzyme intramolecularly. This reaction was retarded in the presence of the coenzyme, whereas 4-nitrobenzaldehyde had no effect. The results suggest the presence of reactive amino groups at the coenzyme binding site of aldehyde reductase.

Alcohol Oxidoreductases↗
PubMed1978

Kinetics of chlormethiazole in patients with alcohol withdrawal manifestations.

Chlormethiazole administered orally to patients in mild degrees of alcohol withdrawal was generally rapidly absorbed, showed a rapid distributive phase, and had an elimination phase 1 1/2 of 2.6 to 4.7 hr. The plasma concentrations of drug attained following higher oral doses were greater than is usually the case with augmentation of dose. Intravenously infused chlormethiazole in similar patients produced relatively high plasma concentrations of the drug, with distributive and eliminative 1 1/2 similar to those of oral doses. These pharmacokinetic patterns in alcoholic patients more closely resemble those previously reported for normal young subjects than they do for normal aged subjects.

Administration, Oral↗
PubMed1978

A rapid behavioral treatment for needle phobics.

A morbid fear of injections and injection paraphernalia can on occasion seriously compromise both the inpatient and outpatient treatment of medical illnesses. Two individuals with a severe needle phobia were treated using participant modeling. In both cases, this very rapid treatment resulted in a remission of symptoms, that in one case persisted at 1 year follow-up post-treatment.

Adult↗
PubMed1977

Purification and properties of NADPH-dependent aldehyde reductase from human liver.

An aldehyde reductase (EC 1.1.1.2) from human liver has been purified to homogeneity. The enzyme is NADPH-dependent, prefers aromatic to aliphatic aldehydes as substrates, and is inhibited by barbiturates and hydantoins. The following physicochemical parameters were determined: molecular weight, 36,200; sedimentation coefficient, 2.9 S; Stokes radius, 2.65 nm; isoelectric point, pH 5.3; extinction coefficient at 280 nm, 54,300 M-1 cm-1. Results from polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, gel filtration, and ultracentrifugation suggest a monomeric structure. On molecule of NADPH binds to the enzyme causing a red shift of the coenzyme absorption maximum from 340 to 352 nm. The amino acid composition has been determined and a partial specific volume of 0.74 was computed from these data. An alpha-helicity of 7 and 18% was estimated from the ellipticities at 208 and 222 nm, respectively. Combination of the most reactive thiol group with p-mercuribenzoate does not cause loss of catalytic activity. Inactivation occurs when more than one thiol group is modified. The presence of NADPH or NADP+ prevents loss of activity by thiol modification. The comparison of structural features of aldehyde reductase with other monomeric and oligomeric dehydrogenases suggest similarities of aldehyde reductase with octopine dehydrogenase.

Alcohol Oxidoreductases↗
PubMedDate not supplied

[Variants of inborn errors of metabolism with late onset but nevertheless life threatening course].

BACKGROUND: There is a growing number of inborn errors of metabolism (IEM) with late onset but nevertheless life threatening course. PATIENTS: Patients with late onset variants of urea cycle defects, fatty acid oxidation defects and organic acidurias are demonstrated. METHODS: Biochemical, enzymatic, molecular methods and especially tandem mass spectrometry (TMS) are used for diagnostic purposes. RESULTS: IEM variants with late onset are difficult to be detected. TMS has some advantages as the simple sampling of dried blood on filter paper cards and the simultaneous detection of a broad spectrum of disturbances in amino acids and acylcarnitines. This may facilitate a prompt diagnosis. Asymptomatic persons not only carry an unrecognized risk for severe metabolic decompensation but also pass on their mutation of IEM and the associated disease risk to the next generation (Non-disease). CONCLUSION: TMS, which is used in newborn screening centers is very convenient to establish a prompt diagnosis in some unexpected late onset metabolic crisis following surgeries, infections or other catabolic stress. Furthermore TMS may be a suitable and rapid adjunct method to improve transplantation management.

Adult↗
PubMedDate not supplied

[Carnitine deficiency and carnitine therapy in a patient with Rett syndrome].

BACKGROUND: Rett syndrome can be diagnosed only clinically. Several biochemical abnormalities are known, but none of them is characteristic. To our knowledge only one study on carnitine deficiency and one case of successful carnitine therapy have been reported. PATIENT: A five years old girl with normal milestones in the first months of life became retarded in the second year with muscle hypotonia of unknown cause and loss of known abilities. Later on recurrent washing movements of the hands, hyperventilation and microcephaly were observed and the diagnosis of Rett syndrome was established. METHOD: A muscle biopsy was performed for the determination of enzymes of the respiratory chain and polarographic respirometry in permeabilized muscle fibres at the age of 3 1/2 years. Carnitine in plasma and urine was determined before and during a therapy with carnitine. RESULTS: The activities of some enzymes of the respiratory chain were slightly decreased as was oxygen consumption in the permeabilized muscle fibres. However muscle morphology and histochemistry were normal. With normal carnitine in the muscle plasma carnitine was clearly decreased but showed a normal ratio of acylcarnitine to free carnitine. Carnitine substitution was started at the age of 3 1/2 years with 75 mg/kg/day and was later increased to 150 mg/kg/day. The treatment showed not only a normalisation of plasma carnitine but also an improvement of physical activity, muscle hypotonia, communication and sleep time. A wash out for one month and resumption of therapy confirmed the efficacy of this regime. CONCLUSIONS: The reason for the carnitine deficiency in the patient with Rett syndrome is not known. A primary carnitine deficiency is excluded by normal muscle carnitine. An explanation for the efficacy of the carnitine therapy is not known, although one could speculate that carnitine provides a transport system for acetyl groups, stimulates acetylcholine formation in the brain and in this way improves the disturbance of the cholinergic system.

Biopsy↗