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PubMed1997

Determination of p-hydroxymandelic acid enantiomers in urine by high-performance liquid chromatography with electrochemical detection.

High-performance liquid chromatography (HPLC) with electrochemical detection using a chiral ligand-exchange column was developed for the enantioselective determination of p-hydroxymandelic acid (HMA), a metabolite of synephrine, with high sensitivity. A good linear relationship between current ratio and amount was noted for 0.5-500 pmol HMA, with a correlation coefficient of 0.999 for each HMA enantiomer. The relative standard deviation (R.S.D.) was 1.6% at 100 pmol d-HMA and 2.2% at 100 pmol l-HMA. The detection limit of each HMA enantiomer was 0.5 pmol (signal to noise ratio, S/N = 3). By this method, HMA in Citrus unshiu and in urine following the ingestion of C. unshiu was determined. Although no HMA was found in c. unshiu, d- and l-HMA were present in urine after the ingestion of C. unshiu. The time courses of HMA and conjugated synephrine enantiomers excreted in urine following the ingestion of C. unshiu for 24 h could be monitored. This method should prove applicable to the study of synephrine metabolism.

Adult↗
PubMed1991

The influence of dietary restriction, germ-free status, and aging on adrenal catecholamines in Lobund-Wistar rats.

Adrenal catecholamines (CA) were measured in 6-, 18-, and 30-mo Lobund-Wistar rats (LWR) maintained under germ-free or conventional conditions and fed either ad libitum or a restricted (70% of adult ad libitum) diet. Levels of dopamine (DA), norepinephrine (NE), epinephrine (E), and dihydroxymandelic acid (DHMA) were determined by HPLC-EC. Compared with values from 6- and 18-mo rats, mean adrenal weight, DA and NE content and concentration, and E content were increased in the 30-mo rats; E concentration was not. The ratio of E:NE declined in the 30-mo group. Germ-free status and dietary restriction had little effect in modulating these age-related changes. Reanalysis of adrenal weights of 30-mo rats revealed two clear subgroups, hyperplastic and non-hyperplastic; the data from hyperplastic adrenals revealed an exaggerated form of the "aged" CA profile, whereas data from the nonhyperplastic adrenals more closely resembled that of younger rats. Thus, aging in LWR is associated with adrenal hyperplasia and a tendency toward elevated adrenomedullary stores of DA and NE, while E stores are maintained near levels found in young rats.

Adrenal Glands↗
PubMed1994

High-resolution two-part basic urea gels for analysis of venom phospholipase A2 isoforms.

The performance of acidic and basic urea polyacrylamide gels has been improved by adopting a two-part gel system with a concentration discontinuity to act as a stacking boundary and by increasing the urea concentration to 8 M. The contributions of primary amino-group and guanidino-group ionizations to mobility have been evaluated by acetylation and phenyl glyoxal treatment respectively. The chromogenic PLA2 detection method of Shier and Trotter (Analyt. Biochem. 87, 604, 1978) has been modified for use with basic urea PAGE. The results have confirmed the major findings of other workers, but have demonstrated the presence of many hitherto uncharacterised isoforms of PLA2 in a variety of whole snake venoms. The basic urea PAGE (BG) method is proposed as the basis of a simple and rapid method for the classification of PLA2 isoforms which should allow unambiguous identification of isoforms by referring bands for purified material to the isoform content of whole venoms.

Acetylation↗
PubMed1976

Metabolic demethylation of the insecticide dimethylvinphos in rats, in dogs, and in vitro.

1. The alkenyl phosphate insecticide, dimethylvinphos, is rapidly metabolized and eliminated by rats and dogs. 2. Metabolism proceeds via demethylation followed by the hydrolysis of desmethyl dimethylvinphos to 2,4-dichlorophenacyl chloride which is further metabolized mainly to 2,4-dichloromandelic acid, 1-(2,4-dichlorophenyl)ethanol (glucuronide) and 2,4-dichlorphenylethanediol (glucuronide). 3. The dechlorination of 2,4-dichlorophenacyl chloride to 2,4-dichloroacetophenone proceeds via the spontaneous formation of S-(2,4-dichlorophenacyl) glutathione which is converted to the ketone by an enzyme-catalysed glutathione-dependent reaction. 4. Demethylation of dimethylvinphos occurs in liver fractions via the action of two enzymes: glutathione S-methyl transferase in the cytosol, and microsomal mono-oxygenase. The relatively high activities of both enzymes in dog liver (compared with rat liver) partly account for the observed differences in metabolism and toxicity of dimethylvinphos in the two species. 5. The glutathione transferase is enhanced twofold by pre-treatment of rats with 0-1% phenobarbital in their drinking water. This treatment also induces the microsomal demethylation 45-fold and results in a greater than 13-fold protective effect against the acute toxic effects of dimethylvinphos.

Animals↗
PubMed1976

Synergy of mecillinam, a beta-amidinopenicillanic acid derivative, combined with beta-lactam antibiotics.

Mecillinam, a beta-amidinopenicillanic acid derivative, was combined with ampicillin, amoxicillin, carbenicillin, cephalothin, cefamandole, and cefoxitin and tested against most members of the Enterobacteriaceae and Pseudomonas. Synergy was demonstrated with selected isolates of most of the organisms tested. Isolates highly susceptible to mecillinam (minimum inhibitory concentration, <0.8 mug/ml) were not synergistically inhibited by addition of another beta-lactam antibiotic. Synergy of mecillinam and a beta-lactamase-resistant penicillin, cloxacillin, was demonstrated. In media of osmolality >10 mOsm or of conductivity >6 mS, mecillinam and beta-lactam antibiotics showed synergy in most instances, whereas at low osmolality and conductivity the activity of mecillinam is so great that synergy cannot be demonstrated. The proportion of mecillinam to beta-lactam antibiotic that will be synergistic ranged from 100:1 to 1:1 to 1:100. Mecillinam did not increase the activity, minimum inhibitory concentration or minimum bactericidal concentration values, of beta-lactam compounds against streptococci, staphylococci, clostridia, listeria, or bacteroides. Synergy was not demonstrated with combinations of mecillinam and aminoglycosides (kanamycin, gentamicin, tobramycin, amikacin), chloramphenicol, tetracycline, or polymyxins.

Azepines↗
PubMed2003

Sensitive determination of oxybutynin and desethyloxybutynin in dog plasma by LC-ESI/MS/MS.

A sensitive and selective liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed for the quantification of oxybutynin and desethyloxybutynin in dog plasma. Diazepam was used as internal standard, with plasma sample extracted using n-hexane and back-extracted using hydrochloric acid. A centrifuged lower layer (aqueous layer) was injected into a C(18) XTerra MS column (2.1 x 30 mm(2)) with 3.5 microm particle size. The analytical column lasted for at least 500 injections. The mobile phase was composed of 90% methanol, with flow rate at 200 microl/min. The mass spectrometer was operated in positive ion mode using electrospray ionization. Nitrogen was used as the nebulizer gas and argon was used as the collision gas. Using MS/MS with multiple reaction monitoring (MRM) mode, oxybutynin and desethyloxybutynin were detected without severe interferences from plasma matrix. Oxybutynin produced a protonated precursor ion ([M+H](+)) at m/z 358 and a corresponding product ion at m/z 142. Desethyloxybutynin produced a protonated precursor ion ([M+H](+)) at m/z 330 and a corresponding product ion at m/z 96. And internal standard (diazepam) produced a protonated precursor ion ([M+H](+)) at m/z 285 and a corresponding product ion at m/z 193. Detection of oxybutynin and desethyloxybutynin in dog plasma were accurate and precise, with detection limit at 0.1 ng/ml. This method has been successfully applied to a study of oxybutynin and desethyloxybutynin in dog plasma.

Animals↗
PubMed2002

Oxybutynin chloride: alterations in drug delivery and improved therapeutic index.

Oxybutynin chloride (Ditropan, Alza) is widely regarded as the most efficient antimuscarinic agent for the treatment of bladder detrusor dysfunction resulting in urinary urgency, frequency and urge incontinence. Oxybutynin metabolism occurs primarily in the proximal gastrointestinal tract and the hepatic circulation and is mediated by the cytochrome P450 3A4 isozyme. The major degradation products are desethyloxybutynin, which possesses pharmacological activity, and phenylcyclohexylglycolic acid, which is metabolically inert. A major limitation to long-term compliance with immediate-release oxybutynin remains the necessity for twice- or thrice-daily dosing regimens to provide sustained pharmacological efficacy. Side effects induced by cytochrome P450 metabolism of oxybutynin into the primary metabolite desethyloxybutynin within the gut wall substantially affect the tolerability of the compound within the individual. The oral osmotic delivery system provides unique advantages for drug delivery and substantially alters the tolerability profile of the oxybutynin chloride compound. This extended-release formulation consists of a two component core encapsulated by a semi-permeable membrane. The osmotic gradient between the surrounding environment and the inner core of the delivery system remains constant and water absorption within the capsule is controlled by the semipermeable membrane causing a controlled release of drug, which is sustained over 24 h. Herein are reviewed the various pre- and post-approval trials which have documented the overall therapeutic index of the oral osmotic oxybutynin (Ortho-McNeil Pharmaceuticals). Subsequent post-market surveillance issues are reviewed as are new developments in oxybutynin delivery.

Animals↗
PubMed1968

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs.

Intravenous administration of tritium-labeled 3,4-dihydroxyphenylalanine (dopa) to human subjects resulted in the labeling of endogenous catecholamines and vanillylmandelic acid (VMA). Determination of the changes in specific activity of these compounds with time in fractional collections of urine and in cardiac biopsies from patients undergoing corrective cardiac surgery permitted estimation of apparent turnover rates. The average half-time of the exponential decline in specific activity of labeled urinary norepinephrine was about 8 hr and that of VMA was 11-16 hr in five normal subjects. No significant differences from normal were observed in eight patients with essential hypertension. The average half-life of norepinephrine was only 5 hr in cardiac patients undergoing surgery, and the levels and rate of decline of cardiac norepinephrine specific activity correlated well with the exponential phase of the urinary disappearance curve. There were significant effects of treatment with alpha-methyltyrosine, reserpine, and pargyline hydrochloride on the labeling and apparent turnover rates of norepinephrine and VMA; the effects noted were consistent with known actions of these three drugs. It is suggested that the technique used is a suitable means of assessing "over-all" catecholamine metabolism in man, particulary if combined with quantitative assay of urinary catecholamine metabolites.

Adolescent↗
PubMed1987

The effect of cyclandelate on cholesterol metabolism in patients with familial hypercholesterolaemia.

Heterozygous familial hypercholesterolaemia (HtFH) is associated with an increased risk of coronary artery disease. Prevention is possible by increasing the number of functioning receptors of low density lipoproteins (LDLs) in the liver. This is partly achieved by treatment with bile acid sequestrants, such as cholestyramine, but the effect is limited because of a concomitant increase in cholesterol synthesis. It was the purpose of this study to determine whether the increase in cholesterol synthesis could be influenced by treatment with cyclandelate, since it is known that cyclandelate inhibits cholesterol synthesis in rats. Ten patients received cyclandelate (3.2 g daily in 2 doses) or placebo in a double-blind cross-over study, with each treatment period of 3 months' duration. During these periods, treatment with cholestyramine (16 g daily) was continued. No evidence was found of inhibition of cholesterol synthesis by cyclandelate, as indicated by the serum concentration of the cholesterol precursor, lanosterol, which remained unchanged. Neither the serum concentration of LDL, nor those of high density lipoprotein (HDL) cholesterol, apolipoprotein B, A-I or A-II, were affected. Thus, it can be concluded that treatment with cyclandelate was not effective in lowering serum cholesterol concentrations in patients with familial hypercholesterolaemia who received concomitant cholestyramine therapy.

Adult↗
PubMed1991

A continuous spectrophotometric method for the determination of diphenolase activity of tyrosinase using 3,4-dihydroxymandelic acid.

A continuous spectrophotometric method for the rapid determination of diphenolase activity of tyrosinase is described. It uses 3,4-dihydroxymandelic acid (DOMA) as the substrate of tyrosinase and measures the final product, 3,4-dihydroxybenzaldehyde (DOBA). The spectrum of this product shows a bathochromic displacement of its absorbance maximum when the pH increases. The optimization of the method is described by using tyrosinase from several biological sources, whose enzymatic activities show different optimal pH. Thus, the enzymatic activity of mushroom tyrosinase was assayed at pH 7.5 and monitored at 350 nm (epsilon 350 pH 7.5 (DOBA) = 15,200 M-1 cm-1), whereas the spectrophotometric experiments with grape tyrosinase were carried out at pH 3.0 and monitored at 310 nm (epsilon 310 pH 3.0 (DOBA) = 9200 M-1 cm-1). The method for mushroom tyrosinase was found to be 50-fold more sensitive than the commonly used dopachrome assay, whereas for grape tyrosinase the method was found to be threefold more sensitive than the commonly used o-quinone production assay. The great solubility and stability of the chromophoric product, DOBA, as well as its high molar absorptivities at any pH, enable the method to be employed to determine the diphenolase activity of tyrosinase from different biological sources.

Benzaldehydes↗
PubMed2006

Biantennary glycans as well as genetic variants of alpha1-acid glycoprotein control the enantioselectivity and binding affinity of oxybutynin.

PURPOSE: The purpose of this study was to investigate the role of biantennary branching glycans of alpha1-acid glycoprotein (AGP) and its genetic variants in the enantioselective binding of oxybutynin (OXY). METHOD: Human native AGP was separated using imminodiacetate-copper (II) affinity chromatography into two fractions, the A variant and a mixture of the F1 and S variants (F1-S). These fractionated AGPs were further separated by concanavalin A affinity chromatography into two fractions, with and without biantenarry glycans. An on-line high-performance liquid chromatography (HPLC) system consisting of a high-performance frontal analysis column, an extraction column, and an analytical HPLC column was developed to determine the binding affinities of OXY enantiomers for respective AGP species. RESULTS: The total binding affinity as well as the enantiomeric selectivity of OXY in the F1-S mixed variant was significantly higher than that for the A variant, indicating that the chiral recognition ability of native AGP for the OXY enantiomers highly depends on the F1-S mixed variant. Furthermore, not only the genetic variants but also bianntenary glycans of AGP affect the binding affinity of OXY and are also responsible for the enantioselectivity. CONCLUSIONS: Both genetic variants and glycan structures significantly contribute to the enantioselectivity and the binding affinity of OXY.

Carbohydrate Conformation↗
PubMed1984

Plasma levels of free and total catecholamines and two deaminated metabolites in man--rapid deconjugation by heat in acid.

We have described a procedure for deconjugation of plasma catecholamines, norepinephrine (NE), epinephrine (E) and dopamine (DA) and two catecholamine metabolites 3,4-dihydroxymandelic acid (DOMA) and 3,4-dihydroxyphenylglycol (DOPEG). Heat at 100 degrees C of the acidified specimen, pH 0.8, produced complete deconjugation of catecholamines in 7 minutes and of metabolites in 5-7 minutes. Subsequently all five products were simultaneously measured with a radioenzymatic assay. However, hydrolysis for 7 minutes produced approximately a loss of 5% in DA and E, 15% in NE and 50% in the metabolites. The percent of free compound in the plasma of 11 normotensive and healthy subjects was 23 +/- 16 for NE, 20 +/- 8 E, 0.8 +/- 1 DA, 20 +/- 7 DOMA and 42 +/- 12 for DOPEG. Similar results were obtained in a random specimen of six patients with primary hypertension. In a group of four patients with pheochromocytoma free levels of NE, DOPEG and DOMA were significantly greater than in the other two groups, whereas conjugates were not. The intravenous administration of NE or the activation of sympathetic nervous system by standing combined with exercise for 15 minutes did not produce a change in the levels of plasma conjugates. These findings suggest that short changes in plasma catecholamines are better reflected in the free than the conjugated part.

Catecholamines↗
PubMed2006

Skin permeation enhancement potential of Aloe Vera and a proposed mechanism of action based upon size exclusion and pull effect.

The aim of this study was to determine in vitro the potential of Aloe Vera juice as a skin permeation enhancer; a secondary aim was to probe the extent to which Aloe Vera itself permeates the skin. Saturated solutions of caffeine, colchicine, mefenamic acid, oxybutynin, and quinine were prepared at 32 degrees C in Aloe Vera juice and water (control) and used to dose porcine ear skin mounted in Franz diffusion cells with water as receptor phase. Receptor phase samples were taken over a 48 h period and permeants determined by reverse-phase HPLC. For caffeine and mefenamic acid no significant enhancements occurred between Aloe Vera and water as vehicles (p>0.05). However, for colchicine, oxybutynin and quinine the presence of Aloe Vera within the formulation provided enhancements (p < or = 0.05). Enhancement potential was dependent upon the molecular weight of the drug in formulation, with the enhancement effect attributable to as yet unidentified components within the Aloe Vera. Colchicine, with a molecular weight of 399.44, achieved the best enhancement with an enhancement ratio of 10.97. No correlation with lipophilicity was apparent. In a further experiment, where freeze-dried Aloe Vera was reconstituted at 200% residue level, permeation of quinine was 2.8 x that from normal Aloe Vera, providing further evidence for the presence of an enhancing factor within Aloe Vera. Certain, although unidentified, components of Aloe Vera readily permeated skin and the relative amount by which they permeated skin was inversely related to the molecular weight of the drug in solution, thus enhancement ratio. A new mechanistic rationale is proposed whereby larger drug solutes inhibit the permeation of Aloe Vera components, but also are then able to interact more effectively with the enhancing factor and be subject to the pull effect.

Aloe↗
PubMed2002

Plasma protein binding study of oxybutynin by high-performance frontal analysis.

Plasma protein binding of oxybutynin (OXY) was investigated quantitatively and enantioselectively using high-performance frontal analysis (HPFA). An on-line HPLC system which consists of HPFA column, extraction column and analytical column was developed to determine the unbound concentrations of OXY enantiomers in human plasma, in human serum albumin (HSA) solutions, and in human alpha1-acid glycoprotein (AGP) solutions. OXY is bound in human plasma strongly and enantioselectively. The bound drug fraction in human plasma containing 2-10 microM (R)- or (S)-OXY was higher than 99%, and the unbound fraction of (R)-OXY was 1.56 times higher than that of (S)-isomer. AGP plays the dominant role in this strong and enantioselective plasma protein binding. The total binding affinities (nK) of (R)- and (S)-OXY to AGP were 6.86 x 10(6) and 1.53 x 10(7) M(-1), respectively, while the nK values of (R)- and (S)-OXY to HSA were 2.64 x 10(4) and 2.19 x 10(-4) M(-1), respectively. The binding affinity of OXY to AGP is much higher than that to HSA, and shows high enantioselectivity (SIR ratio of nK values is 2.2). It was found that both enantiomers are bound competitively at the same binding site on an AGP molecule. The binding property between OXY and low density lipoprotein (LDL) was investigated by using the frontal analysis method incorporated in high-performance capillary electrophoresis (HPCE/FA). It was found the binding is non-saturable and non-enantioselective.

Blood Proteins↗
PubMed1985

Plasma noradrenaline and its deaminated metabolites in essential hypertension and pheochromocytoma.

Dihydroxyphenylglycol (DOPEG) is a metabolite of noradrenaline (NA) in the sympathetic nerve endings, and dihydroxymandelic acid (DOMA) is one in the extraneuronal tissues. The measurement of plasma DOPEG and DOMA were evaluated with NA as one of the clinical indices of sympathetic nerve activity. These were measured in essential hypertension and also applied for diagnosis of pheochromocytoma. Plasma DOPEG levels were correlated with NA. Plasma NA and DOPEG were decreased after oral administration of clonidine (150 micrograms) and plasma DOPEG levels were slowly increased after standing. Therefore, plasma DOPEG seemed to be useful as one of the rather stable indices of the sympathetic nerve activity. Plasma NA and DOPEG levels in WHO stage I essential hypertension were higher than those in normotensive controls. Observed normal plasma noradrenaline and DOPEG levels in stage II reflect the normalized sympathetic tone in this stage. The elevation of plasma NA and DOMA levels in stage III seemed to be at least partly explained by renal function disturbance. In patients with pheochromocytoma, despite of the marked elevation of plasma NA and DOMA, plasma DOPEG showed only three-fold elevation and the ratio DOPEG/NA was reduced. The simultaneous measurement of plasma NA, DOPEG and DOMA is useful to evaluate sympathetic nerve activity in essential hypertension and to differentiate pheochromocytoma in hypertension.

Adrenal Gland Neoplasms↗
PubMed1968

Present status of different mass screening procedures for phenylketonuria. Medical Research Council Working Party on phenylketonuria.

The Phenistix screening test for phenylketonuria in newborn infants, when used routinely at the recommended age of 4 to 6 weeks, passes as normal a substantial proportion-perhaps between a quarter and a half-of children with the disease, who are then diagnosed only after brain damage has occurred. Screening procedures based on three other tests-namely, the paper chromatography test for o-hydroxyphenylacetic acid in urine, the Guthrie test for phenylalanine in blood, and a modification of the Guthrie test for phenylalanine in urine-have been compared with each other and with the Phenistix test in a special field inquiry. Each of the three tests is more efficient than the Phenistix test for the detection of phenylketonuria at an early age.A full appraisal indicates that the Guthrie test on blood would be the most satisfactory of the three tests to replace the Phenistix test as a screening procedure. Routine use of this would involve comprehensive arrangements for obtaining a single specimen of blood by heel-prick from every newborn infant at the age of 6 days or more, but preferably not later than 14 days, and for the rapid and economical processing of the specimens and skilled interpretation of the results at a few laboratory centres. These requirements have not proved difficult to meet in practice in the area where this procedure has been studied.A positive screening test result does not signify a firm diagnosis of phenylketonuria, but is an indication for fuller investigation, most suitably at one of a small number of centres specializing in the management of phenylketonuria and other inborn errors of metabolism.

Age Factors↗
PubMed1972

Biological properties of three 3-heterocyclic-thiomethyl cephalosporin antibiotics.

Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties. All three compounds are active in vitro against a variety of gram-positive and gram-negative bacteria. Minimal inhibitory concentrations (MIC) of these bactericidal antibiotics were not significantly affected by changes in pH or NaCl content of nutrient broth, or by the use of different inoculum sizes. However, agar-dilution MIC values were generally two- to fourfold lower than the MIC values in comparable broth-dilution tests. Stability to cephalosporinase by two of the compounds extended their antibacterial spectra over cephalothin and cephaloridine to include strains of Enterobacter sp. and indole-positive Proteus sp. Binding to serum proteins of the new cephalosporins was intermediate between cephalothin and cephaloridine. Excellent concentrations of the antibiotics were attained in mouse blood, after subcutaneous administration of 20 mg per kg. In vitro biological characteristics of the antibiotics were verified by successful therapy of experimental mouse infections. Regression lines were calculated to show the correlation of agar-dilution MIC values with zones of inhibition by the disc testing procedure. Because each of the three new cephalosporins has certain advantageous properties over cephalothin and cephaloridine, additional toxicological and pharmacological data should be obtained for all three compounds.

Amidohydrolases↗
PubMed2002

Norepinephrine metabolism in neuron: dissociation between 3,4-dihydroxyphenylglycol and 3,4-dihydroxymandelic acid pathways.

AIM: To investigate the pre-synaptic metabolism of norepinephrine (NE), judged by variations in plasma concentration of 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxymandelic acid (DOMA). METHODS: Pithed and electrically stimulated (2.5 Hz) rats were given intravenous infusion of exogenous NE (6 nmol . kg-1 . min-1). Plasma NE, DHPG, DOMA, and the activities of mono- amine oxidases (MAO) were measured with the radio-enzymatic assay. RESULTS: Exogenous NE induces an about 100-fold increase in plasma NE concentration while blood pressure remained within normal limits. A 12-fold increase in plasma DHPG and 1.2-fold increase for DOMA were observed. When NE transportation across the pre-synaptic membrane was inhibited by desipramine (2 mg/kg, iv), a great reduction in plasma DHPG concentration (about 25 % of control) was observed while DOMA remained unchanged. When MAO-A activity was inhibited to 25 % of control by clorgyline (2 mg/kg, iv) and MAO-B to 30 % by deprenyl, the plasma DHPG and DOMA concentrations were reduced to 15 % and 70 % of controls, and to 26 % and 76 % of controls, respectively. When clorgyline and deprenyl were combined, plasma DHPG was vanished (less than 2 % of control) while plasma DOMA remained in the same range (72 % of control). CONCLUSION: The metabolizing system of NE in pre-synapse, associating with the pre-synaptic reuptake plus oxidative deamination on the external membrane of mitochondria, is predominant for the reduction to DHPG.

Animals↗