Functional differences between dimeric and octameric mitochondrial creatine kinase
Kaldis, P. LU
and Wallimann, T.
(1995)
In Biochemical Journal
308(2).
p.623-627
- Abstract
Mitochondrial creatine kinase (Mi-CK) consists of octameric and dimeric molecules that are interconvertible. In the present study, the kinetic properties of purified chicken heart Mi-CK (Mi(b)-CK) dimers and octamers were investigated separately under highly controlled conditions. Gel-permeation chromatography was performed before and after kinetic measurements in order to clearly define the proportions of octamers and dimers. 'Dimeric' Mi-CK solutions consisted of ≥90% dimers throughout the experiment whereas 'octameric' Mi-CK solutions consisted in the beginning of 90% octamers, but upon measuring with the highest concentrations of creatine (Cr) and ATP approximately one-third of the octamers dissociated into dimers. These proper... (More)
Mitochondrial creatine kinase (Mi-CK) consists of octameric and dimeric molecules that are interconvertible. In the present study, the kinetic properties of purified chicken heart Mi-CK (Mi(b)-CK) dimers and octamers were investigated separately under highly controlled conditions. Gel-permeation chromatography was performed before and after kinetic measurements in order to clearly define the proportions of octamers and dimers. 'Dimeric' Mi-CK solutions consisted of ≥90% dimers throughout the experiment whereas 'octameric' Mi-CK solutions consisted in the beginning of 90% octamers, but upon measuring with the highest concentrations of creatine (Cr) and ATP approximately one-third of the octamers dissociated into dimers. These proper controls enabled us to pinpoint the observed kinetic differences between dimers and octamers solely to the oligomeric state of Mi(b)-CK. Both dimeric and octameric Mi-CK displayed synergism in substrate binding (K(d) values are higher than K(m) values), meaning that binding of the first substrate facilitates subsequent binding of the second substrate. Most interestingly, K(m)(Cr) and K(d)(Cr) values are both 2-3 times higher for octameric than for dimeric Mi-CK. Thus, at low Cr concentrations, the dimer is kinetically favoured for the forward direction of the reaction (phosphorylcreatine synthesis) compared with the octamer. The possible physiological significance of the lower K(d)(Cr) value of dimeric versus octameric Mi(b)-CK, as well as the apparent negative cooperativity of ATP binding at higher [Cr], are discussed within the context of a possible functional role for dimeric Mi(b)-CK in vivo.
(Less)
- author
- Kaldis, P.
LU
and Wallimann, T.
- publishing date
- 1995-01-01
- type
- Contribution to journal
- publication status
- published
- in
- Biochemical Journal
- volume
- 308
- issue
- 2
- pages
- 623 - 627
- publisher
- Portland Press
- external identifiers
-
- pmid:7772050
- scopus:0029043818
- ISSN
- 0264-6021
- DOI
- 10.1042/bj3080623
- language
- English
- LU publication?
- no
- id
- b60223cc-03d0-4219-8c59-f5ead809529c
- date added to LUP
- 2019-09-18 14:38:23
- date last changed
- 2024-01-01 20:51:53
@article{b60223cc-03d0-4219-8c59-f5ead809529c,
abstract = {{<p>Mitochondrial creatine kinase (Mi-CK) consists of octameric and dimeric molecules that are interconvertible. In the present study, the kinetic properties of purified chicken heart Mi-CK (Mi(b)-CK) dimers and octamers were investigated separately under highly controlled conditions. Gel-permeation chromatography was performed before and after kinetic measurements in order to clearly define the proportions of octamers and dimers. 'Dimeric' Mi-CK solutions consisted of ≥90% dimers throughout the experiment whereas 'octameric' Mi-CK solutions consisted in the beginning of 90% octamers, but upon measuring with the highest concentrations of creatine (Cr) and ATP approximately one-third of the octamers dissociated into dimers. These proper controls enabled us to pinpoint the observed kinetic differences between dimers and octamers solely to the oligomeric state of Mi(b)-CK. Both dimeric and octameric Mi-CK displayed synergism in substrate binding (K(d) values are higher than K(m) values), meaning that binding of the first substrate facilitates subsequent binding of the second substrate. Most interestingly, K(m)(Cr) and K(d)(Cr) values are both 2-3 times higher for octameric than for dimeric Mi-CK. Thus, at low Cr concentrations, the dimer is kinetically favoured for the forward direction of the reaction (phosphorylcreatine synthesis) compared with the octamer. The possible physiological significance of the lower K(d)(Cr) value of dimeric versus octameric Mi(b)-CK, as well as the apparent negative cooperativity of ATP binding at higher [Cr], are discussed within the context of a possible functional role for dimeric Mi(b)-CK in vivo.</p>}},
author = {{Kaldis, P. and Wallimann, T.}},
issn = {{0264-6021}},
language = {{eng}},
month = {{01}},
number = {{2}},
pages = {{623--627}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{Functional differences between dimeric and octameric mitochondrial creatine kinase}},
url = {{http://dx.doi.org/10.1042/bj3080623}},
doi = {{10.1042/bj3080623}},
volume = {{308}},
year = {{1995}},
}