Biochemical studies on Mycobacterium leprae.

Very little information is available on the basic biology of Mycobacterium leprae. It is not known why the organism fails to grow in bacteriological media or in cell cultures and why it has an unusual predilection for certain tissues in the human host where cells derived from the neural crest occur (e.g. skin, peripheral nerves, adrenal medulla). Biochemical studies have revealed that M. leprae contains an unusual form of the enzyme diphenoloxidase which has not been detected in other mycobacteria. The presence of a specific glutamic acid decarboxylase in the organism has been demonstrated. Although a few enzymes of glycolysis and tricarboxylic acid cycle have been investigated, nothing characteristic of the bacterium has been discovered, and how M. leprae derives energy for its survival and proliferation still remains obscure.

Glutamic acid decarboxylase in Mycobacterium leprae.

Suspensions of Mycobacterium leprae purified from the organs (mostly spleen) of experimentally-infected armadillos (Dasypus novemcinctus, Linn) decarboxylated 1-(14C) glutamic acid liberating 14CO2. The reaction was pyridoxal phosphate-dependent and was inhibited by hydroxylamine, suggesting that it is a true amino acid decarboxylase. Loss of the activity at higher temperatures indicated the enzymatic nature of the reaction. Excess substrate or substrate analogs inhibited the decarboxylase whereas alpha-ketoglutarate and glutarate stimulated it. The activity was four times higher at pH 4.5 than at pH 6.8, suggesting that the enzyme is of microbial origin and not derived form the host cells. Armadillo spleen did not decarboxylate the amino acid. The Km value of the enzyme in the organisms was similar to that in Escherichia coli. The results reported here show that glutamate decarboxylase (EC 4.1.1.15) is an inherent metabolic activity of M. leprae, and might explain its unusual neural affinity. Glutamic acid is the most abundant amino acid occurring in the nerve tissue.