Localization and hormonal control of serine dehydratase during metabolic acidosis differ markedly from those of phosphoenolpyruvate carboxykinase in rat kidney.
Serine dehydratase (SDH) is abundant in the rat liver but scarce in the kidney. When administrated with dexamethasone, the renal SDH activity was augmented 20-fold, whereas the hepatic SDH activity was affected little. In situ hybridization and immunohistochemistry revealed that SDH was localized to the proximal straight tubule of the nephron. To address the role of this hormone, rats were made acidotic by gavage of NH(4)Cl. Twenty-two hours later, the SDH activity was increased three-fold along with a six-fold increment in the phosphoenolpyruvate carboxykinase (PEPCK) activity, a rate-limiting enzyme of gluconeogenesis. PEPCK, which is localized to the proximal tubules under the normal condition, spreads throughout the entire cortex to the outer medullary rays by acidosis, whereas SDH does not change regardless of treatment with dexamethasone or NH(4)Cl. When NH(4)Cl was given to adrenalectomized rats, in contrast to the SDH activity no longer increasing, the PEPCK activity responded to acidosis to the same extent as in the intact rats. A simultaneous administration of dexamethasone and NH(4)Cl into the adrenalectomized rats fully restored the SDH activity, demonstrating that the rise in the SDH activity during acidosis is primarily controlled by glucocorticoids. The present findings clearly indicate that the localization of SDH and its hormonal regulation during acidosis are strikingly different from those of PEPCK.
Masuda
Tohru
T
Department of Biochemistry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Japan.
Ogawa
Hirofumi
H
Matsushima
Takako
T
Kawamata
Seiichi
S
Sasahara
Masakiyo
M
Kuroda
Kazunari
K
Suzuki
Yasuhiro
Y
Takata
Yoshimi
Y
Yamazaki
Mitsuaki
M
Takusagawa
Fusao
F
Pitot
Henry C
HC
D000138:Acidosis / Q000139:chemically induced / Q000201:enzymology*; D000315:Adrenalectomy; D000643:Ammonium Chloride / Q000633:toxicity; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D005215:Fasting; D005943:Gluconeogenesis / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D012695:L-Serine Dehydratase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000643:Ammonium Chloride; D003907:Dexamethasone; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D012695:L-Serine Dehydratase