Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria

L.A. Sazanov, J.B. Jackson

Результат исследований: Научные публикации в периодических изданияхстатья

162 Цитирования (Scopus)

Выдержка

H(+)-transhydrogenase (H(+)-Thase) and NADP-linked isocitrate dehydrogenase (NADP-ICDH) are very active in animal mitochondria but their physiological function is only poorly understood. This is especially so in the case of the heart and muscle, where there are no major consumers of NADPH. We propose here that H(+)-Thase and NADP-ICDH have a combined function in the fine regulation of the activity of the tricarboxylic acid (TCA) cycle, providing enhanced sensitivity to changes in energy demand. This is achieved through cycling of substrates by NAD-linked ICDH, NADP-linked ICDH and H(+)-Thase. It is proposed that NAD-ICDH operates in the forward direction of the TCA cycle, but NADP-ICDH is driven in reverse by elevated levels of NADPH resulting from the action of the transmembrane proton electrochemical potential gradient (delta p) on H(+)-Thase. This has the effect of increasing the sensitivity to allosteric modifiers of NAD-ICDH (NADH, ADP, ATP, Ca2+ etc), potentially giving rise to large changes in the net
Язык оригиналаанглийский
Страницы (с-по)109-116
ЖурналFEBS Letters
Том344
Номер выпуска2-3
DOI
СостояниеОпубликовано - 1994
Опубликовано для внешнего пользованияДа

Отпечаток

NADP Transhydrogenases
Isocitrate Dehydrogenase
Mitochondria
Citric Acid Cycle
NADP
NAD
Protons
Substrates
Substrate Cycling
Adenosine Diphosphate
Muscle
Myocardium
Animals
Adenosine Triphosphate
isocitrate dehydrogenase (NADP+)

Цитировать

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title = "Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria",
abstract = "H(+)-transhydrogenase (H(+)-Thase) and NADP-linked isocitrate dehydrogenase (NADP-ICDH) are very active in animal mitochondria but their physiological function is only poorly understood. This is especially so in the case of the heart and muscle, where there are no major consumers of NADPH. We propose here that H(+)-Thase and NADP-ICDH have a combined function in the fine regulation of the activity of the tricarboxylic acid (TCA) cycle, providing enhanced sensitivity to changes in energy demand. This is achieved through cycling of substrates by NAD-linked ICDH, NADP-linked ICDH and H(+)-Thase. It is proposed that NAD-ICDH operates in the forward direction of the TCA cycle, but NADP-ICDH is driven in reverse by elevated levels of NADPH resulting from the action of the transmembrane proton electrochemical potential gradient (delta p) on H(+)-Thase. This has the effect of increasing the sensitivity to allosteric modifiers of NAD-ICDH (NADH, ADP, ATP, Ca2+ etc), potentially giving rise to large changes in the net",
keywords = "Mitochondrion, Tricarboxylic acid cycle, Regulation, Futile cycle",
author = "L.A. Sazanov and J.B. Jackson",
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doi = "10.1016/0014-5793(94)00370-X",
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Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria. / Sazanov, L.A.; Jackson, J.B.

В: FEBS Letters, Том 344, № 2-3, 1994, стр. 109-116.

Результат исследований: Научные публикации в периодических изданияхстатья

TY - JOUR

T1 - Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria

AU - Sazanov, L.A.

AU - Jackson, J.B.

PY - 1994

Y1 - 1994

N2 - H(+)-transhydrogenase (H(+)-Thase) and NADP-linked isocitrate dehydrogenase (NADP-ICDH) are very active in animal mitochondria but their physiological function is only poorly understood. This is especially so in the case of the heart and muscle, where there are no major consumers of NADPH. We propose here that H(+)-Thase and NADP-ICDH have a combined function in the fine regulation of the activity of the tricarboxylic acid (TCA) cycle, providing enhanced sensitivity to changes in energy demand. This is achieved through cycling of substrates by NAD-linked ICDH, NADP-linked ICDH and H(+)-Thase. It is proposed that NAD-ICDH operates in the forward direction of the TCA cycle, but NADP-ICDH is driven in reverse by elevated levels of NADPH resulting from the action of the transmembrane proton electrochemical potential gradient (delta p) on H(+)-Thase. This has the effect of increasing the sensitivity to allosteric modifiers of NAD-ICDH (NADH, ADP, ATP, Ca2+ etc), potentially giving rise to large changes in the net

AB - H(+)-transhydrogenase (H(+)-Thase) and NADP-linked isocitrate dehydrogenase (NADP-ICDH) are very active in animal mitochondria but their physiological function is only poorly understood. This is especially so in the case of the heart and muscle, where there are no major consumers of NADPH. We propose here that H(+)-Thase and NADP-ICDH have a combined function in the fine regulation of the activity of the tricarboxylic acid (TCA) cycle, providing enhanced sensitivity to changes in energy demand. This is achieved through cycling of substrates by NAD-linked ICDH, NADP-linked ICDH and H(+)-Thase. It is proposed that NAD-ICDH operates in the forward direction of the TCA cycle, but NADP-ICDH is driven in reverse by elevated levels of NADPH resulting from the action of the transmembrane proton electrochemical potential gradient (delta p) on H(+)-Thase. This has the effect of increasing the sensitivity to allosteric modifiers of NAD-ICDH (NADH, ADP, ATP, Ca2+ etc), potentially giving rise to large changes in the net

KW - Mitochondrion

KW - Tricarboxylic acid cycle

KW - Regulation

KW - Futile cycle

U2 - 10.1016/0014-5793(94)00370-X

DO - 10.1016/0014-5793(94)00370-X

M3 - Article

VL - 344

SP - 109

EP - 116

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 2-3

ER -