[Normal values for the concentrations of porphyrins and porphyrin precursors].
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A study was carried out among 1414 workers in 14 industries in Singapore to determine the extent of their exposure to lead and their lead absorption. High-level exposure situations found included secondary lead smelting, followed by mixing of lead salt stabilizers and lead storage battery manufacture. Other exposure situations included those relating to lead welding, print shop, wire splicing, leaded paint manufacture, fire-fighting and soldering. Early cases of lead absorption could not be detected by clinical signs alone. Other parameters such as blood lead and delta-aminolaevulinic acid dehydratase had to be used. There was good correlation between a rise in blood lead and a fall in delta-aminolaevulinic acid dehydratase levels.
Delta-aminolaevulinic acid dehydrogenase is a key enzyme in porphyrin synthesis which catalyses the formation of porphobilinogens from two molecules of delta-aminolaevulinic acid. Delta-aminolaevulinic acid dehydratase is a sulphhydryl group enzyme which is inhibited by lead ions and other heavy metal ions. A method has been devised on that basis to determine industrial and ecological lead intoxication. While correlations have been statistically secured between airborne lead concentration, biochemical reactions, inhibition of delta-aminolaevulinic acid dehydratase, and increased discharge of delta-aminolaevulinic acid, determination of enzyme activity cannot be used in situations of high exposure to lead, because inhibition was found to be too strong, and dose-action relationship between actual exposure and biological response were found to provide no information with relevance to industrial medicine. A method less sensitive than determination of delta-aminolaevulinic acid should be preferred for monitoring of higher lead concentrations. Determination of delta-aminolaevulinic acid dehydratase activity is applicable only to low or usual lead exposure.
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Pharmacological properties of 2-amino-4-oxo-5-phosphonopentanoic acid (AOPA) on excitatory amino acids mediated responses have been tested in CA1 rat hippocampal neurones, using intracellular recordings and current and voltage clamp techniques. These properties were compared with those of the well-known NMDA antagonist, D(-)2-amino-5-phosphonopentanoic acid (AP-5). AOPA completely abolished the response to NMDA but had no effects on the responses to AMPA, quisqualate and kainate. In voltage clamp experiments AOPA antagonized NMDA-induced currents and produced a parallel shift of the NMDA concentration-response curve. Schild analysis gave a Kd value of 26 microM. AP-5 also produced a similar shift in this curve with a Kd of 6.9 mu.
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A 7-year follow-up survey on 53 workers was carried out in a lead storage battery factory to evaluate the significance of urinary delta-aminolevulinic acid (ALA) and blood lead in a work environment where lead in the air was considered to be about or less than the current occupational exposure limit. While lead in the blood and ALA in the urine had a good correlation to each other cross-sectionally as well as longitudinally, geometric means of lead concentrations in the workroom air samples which were collected following grid sampling strategy, did not correlate with ALA in urine significantly. On the contrary, the semiannual production of batteries significantly correlated with changes in mean ALA in urine. The questionnaire survey proved that the prolongation in work hours, lead to an increase in the mean ALA in urine as well as a higher incidence of higher-than-normal urinary ALA. The results clearly demonstrated the importance of the biological indicators, such as lead in blood and urinary ALA, as well as the necessity of paying attention to non-industrial hygiene factors, such as the production rate of batteries and the length of the daily shift, for the protection of the workers' health when lead in the air is moderate.
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Cell-free preparations from the unicellular green alga, Chlorella vulgaris, catalyze the conversion of glutamate to delta-aminolevulinate, which is the first committed step in heme and chlorophyll biosynthesis. Most activity remains in the supernatant fraction after centrifugation at 264,000g. Additional activity can be solubilized from the high-speed pellet by treatment with 0.5 M NaCl. After gel filtration through Sephadex G-25, the reaction catalyzed by the high-speed supernatant requires glutamate, ATP, Mg2+, and NADPH. Boiled extract is inactive. The pH optimum is between 7.8 and 7.9 and the temperature optimum is 30 degrees C. Concentrations required for half-maximal activity are 0.05 mM glutamate, 0.4 mM ATP, 6 mM MgCl2, and 0.4 mM NADPH or 0.7 mM NADH. The reaction requires no additional amino donor. Involvement of pyridoxal phosphate in the catalytic mechanism is suggested by sensitivity to pyridoxal antagonists; 50% inhibition is achieved with 5 microM gabaculine or 0.4 mM aminooxyacetate. Involvement of two or more enzymes is suggested by the nonlinear reaction rate dependence on protein concentration. Evidence for the involvement of an activated glutamate intermediate was obtained by product formation after sequential addition and removal of substrates, and by inhibition (80%) with 1 mM hydroxylamine. Protoheme inhibits the activity by 50% at 1.2 microM. Preincubation of the extract with ATP causes stimulation and/or stabilization of the activity compared to preincubation without ATP or no preincubation. In preparations obtained from C. vulgaris strain C-10, which requires light for greening, dark-grown cells yield one-third as much activity as 4-h-greened cells.