Lactate, labelled

The ability of the rat to use lactate, pyruvate, and D-glucose to equal extents in the synthesis of 1-naphthyl D-glucosiduronic acid was demonstrated by Packham and Butler.158 The lactate and pyruvate were labeled with C14 at the carboxyl carbon lactate labeled at Cl and C2 was also used and the D-glucose was uniformly labeled. D-Glucuronate-C14 was utilized for D-glucuronic conjugation on oral administration, but was twenty times as effective after intraperitoneal injection. 

The enzyme Candida utilis 6-phosphogluconate dehydrogenase with carbon-13 enriched to 90 atom% has been obtained by growing the yeast with Relabelled acetic acid as the sole carbon source [186]. Carbon-13 composition had very little, if any, effect on the catalytic properties of the enzyme. Sodium [ RC]lactate has been used to study the conversion of lactate to liver glycogen in the rat. Lactate labelled with C at position 2 and C at position 3 was also used. Carbon-13 was measured by mass spectrometry [187]. Similar experiments were carried out with RC-labelled propionate and C- and C-labelled propionate [188]. 

Some work has been done on the formation of glucuronic acid from smaller fragments (67). Glycerol, labeled at carbon 1, when fed to rats gave a glucuronide with a distribution of radioactivity that would be predicted by a condensation of C3 units. However, lactate labeled at carbon 3 gave a glucosiduronic acid with all the radioactivity at carbon 6. 

Isolated hepatocytes were incubated with lactate labelled with in carbon-2 ([ C-2]lactate) or palmitate labelled with C in all carbon atoms ([U- Qpalmitate) in each case the specific radioactivity of the labelled substrate in the incubation medium was 10 dpm/ imol. In a further series of incubations with [U- Qpalmitate, non-radioactive glutamate was also added. The results are shown in Table 5.11. 

Fig. 2. Identification of fMet on subunit 9 of oligomycin-sensitive ATPase. Sac-charomyces cerevisiae, strain 4D, was grown on SSA 3% lactate, labeled with PH]formate for 6 h, and mitochondria prepared as previously described. Preparation of chloroform-methanol (CM) fractions was done as described by Sierra and Tzagoloff. Sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis was done by the method of Weber and Osborn, with 8% acrylamide for 11 h at 5 mA per gel. The 12-cm gels were cut into 1-mm slices and counted. Different patterns were normalized thru mobility of protein standards and tracking dye. (A) Final purified CM fraction after several ether...

The results of metabolism studies with laboratory animals and livestock indicate that endosulfan does not bioconcentrate in fatty tissues and milk. Lactating sheep administered radiolabeled endosulfan produced milk containing less than 2% of the label. Endosulfan sulfate was the major metabolite in milk (Gorbach et al. 1968). A half-life of about 4 days was reported for endosulfan metabolites in milk from survivors of a dairy herd accidentally exposed to acutely toxic concentrations of endosulfan endosulfan sulfate accounted for the bulk of the residues detected in the milk (Braun and Lobb 1976). No endosulfan residues were detected in the fatty tissue of beef cattle grazed on endosulfan-treated pastures for 31-36 days (detection limits of 10 ppm for endosulfan, 40 ppm for endosulfan diol) the animals began grazing 7 days after treatment of the pastures. Some residues were detected in the fatty tissue of one animal administered 1.1 mg/kg/day of endosulfan in the diet for 60 days. No endosulfan residues were... 

Plasma levels of diisopropyl methylphosphonate were measured in a single lactating Jersey cow after the sixth day of diisopropyl methylphosphonate oral administration (10 mg/kg/day) by gelatin capsule (Ivie 1980). For the first 5 days the cow was given unlabeled compound and fed hay ad libitum. The diisopropyl methylphosphonate administered on the 6th day was labeled with carbon 14. Based on measurements of label in the plasma, absorption in the cow paralleled that in rats and dogs, with the highest concentration detected in the plasma at 2 hours after administration. 

The study of diisopropyl methylphosphonate distribution in a lactating Jersey cow was the only study that used multiple doses of diisopropyl methylphosphonate (Ivie 1980). In this single cow, radioactivity was detected in the blood 2 hours after dosing with [14C]-radiolabeled compound but not in the tissues. The animal had received diisopropyl methylphosphonate in one gelatin capsule for 5 days before the radiolabeled dose was administered. If tissue uptake in the cow was similar to that in dogs, measurements made 2 hours after dosing may not have provided an opportunity to measure tissue uptake of label. After 24 hours, 0.1% of the administered label was found in the cow s milk (Ivie 1980). 

In a single lactating Jersey cow, 30% of a [14C]-radiolabeled dose of 10 mg/kg/day was excreted in the urine 4 hours after dosing, and 84% was excreted in a 96-hour period (Ivie 1980). The amount of label after 96 hours was 7% in the feces and less than 1% in the cow s milk. Before being given the radiolabeled material, the cow had been administered unlabelled diisopropyl methylphosphonate in a gelatin capsule for 5 consecutive days. 

They observed abrupt changes in the slope of Arrhenius plots for reactions catalyzed by NADH oxidase and p-lactate oxidase that correlate well with phase transitions detected by the ESR spectra of the nitroxide spin labels bound covalently to the enzymes (Table 5.4). 

Hydroxylated metabolites are conjugated as glucuronides and sulfates. The balance of products in this last step and their distribution between urine and feces distinguishes the metabolism between humans, rats, and rabbits (Baldwin and Hutson 1980 Bedford et al. 1975b Hutson 1981 Hutson et al. 1975), as discussed in Section 2.3.4. Similarly, studies in lactating cows ingesting radio-labeled endrin in the diet for 21 days suggest metabolic pathways similar to those in rats and rabbits with apparent differences between the 3 species attributed more to differences in biliary versus renal excretion (Baldwin et al. 1976). 

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