Abstract
Extract: Mature human renal cortex contains γ-aminobutyric acid (GABA) at concentrations on the order of 0.2 μmol/g wet wt and about half of that concentration in fetal kidney.
The pyridoxal-5′-phosphate (PLP)-dependent enzyme, L-glutamic acid decarboxylase (GAD), catalyzes the conversion of L-glutamate to GABA. The PLP-saturated GAD activity in post-term (1 day–9 years) renal cortex homogenate is 0.94 ± 0.38 μmol CO2 formed/g wet wt/hr (Table 1). The corresponding GAD activity in fetal renal cortex, in the midtrimester and early third trimester, is 0.28 ± 0.19 μmol CO2 formed/g wet wt/hr (P < 0.01 vs. post-term activity). GAD activity increases during gestation to reach levels at birth equivalent to mature kidney. When corrections are made for the difference in tissue water between fetal and mature kidney, they do not ablate the post-term increase in GAD activity.
Renal GAD was undersaturated with PLP in 12 of 21 specimens examined; 8 of these specimens were of fetal origin (Table 1 and Fig. 2). Undersaturation was revealed when addition of PLP (0.24 mM) to the homogenate stimulated activity by 25 300% in the 12 specimens. GAD activity in rat kidney binds PLP avidly and is always saturated with PLP under the normal laboratory conditions of vitamin B6 nutrition. Undersaturation of renal GAD in man may imply inadequate endogenous availability of vitamin B6 coenzyme.
Speculation: The GABA pathway in mammalian kidney has been implicated in the maintenance of normal acid-base balance. Renal GAD is increased in the postnatal subject relative to fetal GAD activity in support of this hypothesis. Undersaturation of fetal GAD with its PLP-coenzyme in two-thirds of the fetal specimens may have implications concerning intrauterine nutrition and renal development.
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Lancaster, G., Mohyuddin, F. & Scriver, C. Ontogeny of L-Glutamic Acid Decarboxylase and γ-Aminobutyric Acid Concentration in Human Kidney. Pediatr Res 9, 484–487 (1975). https://doi.org/10.1203/00006450-197505000-00005
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DOI: https://doi.org/10.1203/00006450-197505000-00005