Publicação
CoQ0 0 hysteresis and inhibition of the cytochrome b5 reductase activity of human Cb5R by CoQ0 and CoQ10.
| Resumo: | BACKGROUND: In this study, the effect of ubiquinone (CoQ 10) and its soluble analogue (CoQ 0) was measured on the NADH:Cb 5 reductase activity of recombinant human membrane and soluble Cb 5R, respectively using soluble Cb 5 as a substrate. The aim of this study was to determine whether quinones are inhibitors and can induce a hysteretic modulation of the activity, similar to that described for Cb 5 reduction in microsomal systems. RESULTS: CoQ 0 and CoQ 10 inhibit the NADH:cytochrome b 5 reductase activity of soluble and membrane Cb 5R respectively, using soluble Cb 5 as an electron acceptor. However, only CoQ 0 induced hysteresis of the soluble Cb 5R isoform. The addition of CoQ 0 induced the appearance of a lag phase, whose duration increased with the concentration of CoQ 0 and decreased with higher concentrations of soluble Cb 5 or Cb 5R. Additionally, a concentration-dependent decrease in the maximum rate of reduction and the appearance of positive cooperativity was observed in the presence of CoQ 0 which resulted in lower K M values for Cb 5. This suggests the formation of a CoQ 0:Cb 5R complex altering the interaction between the reductase and Cb 5 which increases the affinity for Cb 5. Cyclic voltammetry data support the formation of CoQ 0/protein complex that could be responsible for the hysteretic behavior. CONCLUSIONS: Both quinones inhibit the NADH: cytochrome b 5 reductase activity of human Cb 5R isoforms, but only CoQ 0 triggers hysteresis in the soluble Cb 5R isoform. Our data support the use of fully soluble components for studying hysteresis in this system, as they recapitulate key features of the behavior observed in biological membranes. |
|---|---|
| Autores principais: | Valerio, Gabriel N |
| Outros Autores: | Martinez-Costa, Oscar H; Sanchez-Cabeza, Carlos; Cordas, Cristina M; Samhan-Arias, Alejandro K |
| Assunto: | Cb CbR CoQ Hysteresis Ubiquinone Biochemistry Physiology (medical) SDG 3 - Good Health and Well-being |
| Ano: | 2026 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | BACKGROUND: In this study, the effect of ubiquinone (CoQ 10) and its soluble analogue (CoQ 0) was measured on the NADH:Cb 5 reductase activity of recombinant human membrane and soluble Cb 5R, respectively using soluble Cb 5 as a substrate. The aim of this study was to determine whether quinones are inhibitors and can induce a hysteretic modulation of the activity, similar to that described for Cb 5 reduction in microsomal systems. RESULTS: CoQ 0 and CoQ 10 inhibit the NADH:cytochrome b 5 reductase activity of soluble and membrane Cb 5R respectively, using soluble Cb 5 as an electron acceptor. However, only CoQ 0 induced hysteresis of the soluble Cb 5R isoform. The addition of CoQ 0 induced the appearance of a lag phase, whose duration increased with the concentration of CoQ 0 and decreased with higher concentrations of soluble Cb 5 or Cb 5R. Additionally, a concentration-dependent decrease in the maximum rate of reduction and the appearance of positive cooperativity was observed in the presence of CoQ 0 which resulted in lower K M values for Cb 5. This suggests the formation of a CoQ 0:Cb 5R complex altering the interaction between the reductase and Cb 5 which increases the affinity for Cb 5. Cyclic voltammetry data support the formation of CoQ 0/protein complex that could be responsible for the hysteretic behavior. CONCLUSIONS: Both quinones inhibit the NADH: cytochrome b 5 reductase activity of human Cb 5R isoforms, but only CoQ 0 triggers hysteresis in the soluble Cb 5R isoform. Our data support the use of fully soluble components for studying hysteresis in this system, as they recapitulate key features of the behavior observed in biological membranes. |
|---|