The effect of univalent cations of activities catalyzed bovine-liver propionyl-CoA carboxylase

Giorgio, Anthony J.; Plaut, G.W.E.

doi:10.1016/0005-2744(67)90052-6

Cited by 28 publications

(9 citation statements)

References 16 publications

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“…Secondly, Landman (12) demonstrated that biotin is covalently attached to the carboxylases after the protomers have been assembled and suggested that two holocarboxylase forms may exist, an active and inactive form. This activation, as shown previously for PCC and other carboxylases, may be due to direct interaction of affector molecules with holocarboxylase (6,8,13,17,21,22) or to enzymatic modification of holocarboxylase, such as by phosphorylation (14). Biotin, therefore, may act directly, by stabilizing PCC, or indirectly, by interacting with other metabolic pathways, producing substances or stimulating enzymes which activate preexisting inactive holocarboxylase.…”

Section: Discussionsupporting

confidence: 59%

Stimulation of Propionyl CoA and β-Methylcrotonyl CoA Carboxylase Activities in Human Leukocytes and Cultured Fibroblasts by Biotin

Wolf

Rosenberg

1979

Pediatr Res

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SummaryInitially, it was observed that whereas the propionyl CoA carboxylase (PCC) activity in peripheral blood leukocytes of a 13-month-old girl with isolated PCC deficiency who had been given biotin supplements (4.5 &day) for 6 months was only 3% of control, her BMCC activity was greatly elevated at 20 times control activity. After biotin supplements were discontinued, BMCC activity in leukocyte extracts declined over 3 wk to values just above the normal range with no associated change in PCC activity; readministration of biotin caused her BMCC activity to rise in 3 days to the initial elevated values. These results prompted measurement of PCC and BMCC activities in leukocyte extracts of three normal adults given 20 mg biotin orally per day. Their PCC and BMCC activities increased 2-to Ifold and 4-to 9-fold, respectively, within 7-10 days. After biotin was discontinued, both enzyme activities returned to normal in 4-5 wk. The effect of high concentrations of biotin and BMCC activities was also investigated in cultured fibroblasts from three control subjects. PCC activity increased only 11% in normal fibroblasts grown in medium containing fetal bovine serum and high concentrations of biotin (900 pg/ml). However, PCC and BMCC activities were increased 70-75% and 120-la%, respectively, when confluent normal fibroblasts were incubated in medium containing 10% human serum and 0.1-1.0 pg/ml biotin. This stimulation was independent of the fibroblast growth cycle. Furthermore, cycloheximide failed to inhibit the increase in PCC activity caused by biotin, suggesting that the enhanced activity in fibroblasts was not due to & novo carboxylase synthesis. These studies demonstrate that high concentrations of biotin can stimulate biotin-dependent carboxylases in human tissues, possibly by converting apocarboxylase to holocarboxylase or by activating preexisting inactive holocarboxylase. SpeculationThe stimulation of human propionyl CoA and 8-methylcrotonyl CoA carboxylase activities in peripheral blood leukocytes in vivo and in cultured skin fibroblasts by high concentrations of biotin represents a promising model for investigating the cellular metabolism of biotin in man.pionate, and decreased urinary propionate metabolites after biotin therapy. Deficiencies of two closely related biotin dependent enzymes, PCC and P-methylcrotonyl CoA carboxylase (PMCC; EC 6.4.1.4), were demonstrated in fibroblast extracts from one of these patients (23). Both carboxylase activities returned to normal when these fibroblasts were grown in biotin-supplemented medium (3, 23). PCC deficiency was shown in fibroblasts from a second patient, but PMCC activity before and after biotin administration was not reported (2). The third patient had isolated PCC deficiency with normal PMCC activity in peripheral blood leukocytes and in fibroblast extracts (9). When biotin was added to the fibroblast growth medium, an increase in PCC activity towards the normal range was observed. Although the PCC activity of isolated peripheral blood leukocytes was also s...

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Section: Discussionsupporting

confidence: 59%

Stimulation of Propionyl CoA and β-Methylcrotonyl CoA Carboxylase Activities in Human Leukocytes and Cultured Fibroblasts by Biotin

Wolf

Rosenberg

1979

Pediatr Res

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“…3). Mammalian PCC is localized in the mitochondrial matrix, and is activated by mono-valent cations (K + , NH 4 + , Cs + ) [179–181]. PCC activity is also important for CO 2 fixation in some archaeal organisms [5,6], methanol assimilation in Methylobacterium extorquens [7], acetyl-CoA assimilation in α-proteobacteria [10], 3-hydroxypropionate assimilation in Rhodobacter sphaeroides [11], mycolic acid and methyl-branched long-chain fatty acid biosynthesis in M. tuberculosis [12], and polyketide biosynthesis in Streptomyces and other organisms [13].…”

Section: Propionyl-coa Carboxylase (Pcc)mentioning

confidence: 99%

Structure and function of biotin-dependent carboxylases

Tong

2012

Cell. Mol. Life Sci.

362

338

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Biotin-dependent carboxylases include acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC), geranyl-CoA carboxylase (GCC), pyruvate carboxylase (PC), and urea carboxylase (UC). They contain biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) components. These enzymes are widely distributed in nature and have important functions in fatty acid metabolism, amino acid metabolism, carbohydrate metabolism, polyketide biosynthesis, urea utilization, and other cellular processes. ACCs are also attractive targets for drug discovery against type 2 diabetes, obesity, cancer, microbial infections, and other diseases, and the plastid ACC of grasses is the target of action of three classes of commercial herbicides. Deficiencies in the activities of PCC, MCC or PC are linked to serious diseases in humans. Our understanding of these enzymes has been greatly enhanced over the past few years by the crystal structures of the holoenzymes of PCC, MCC, PC, and UC. The structures reveal unanticipated features in the architectures of the holoenzymes, including the presence of previously unrecognized domains, and provide a molecular basis for understanding their catalytic mechanism as well as the large collection of disease-causing mutations in PCC, MCC and PC. This review will summarize the recent advances in our knowledge on the structure and function of these important metabolic enzymes.

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“…Rather, the occurrence of reaction 7a is supported by the fact that the carboxylases, where investigated, catalyze ATP-32Pi exchange and that maximal rates of exchange are achieved only in the presence of ADP, Me2+, and bicarbonate (Section VI.) (81,(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136). 'Furthermore, the reciprocal ATP-I4C or s2Pi-ADP exchange catalyzed by acyl CoA carboxylases exhibits a requirement for Pi, Mez+, and bicarbonate (81,126,128,133,134).…”

Section: Partial Reactionsmentioning

confidence: 99%

“…Propionyl CoA carboxylases from pig heart (564,565), bovine liver (134,566), and rat liver (549) are activated by certain monovalent cations. Edwards and Keech (565) demonstrated with the enzyme from pig heart that potassium ion reduced the K , for bicarbonate from 8 to 3 mM.…”

Section: Reaction and Mechanismmentioning

confidence: 99%