Biomedical Engineering Reference
In-Depth Information
concentration of LCACoA would be in the low nM range when the acyl-
CoA/ACBP ratio is below one. As this ratio exceeds one, FABP starts
buffering and the level of unbound acyl-CoA was calculated to be less than
0.2µM (Faergeman and Knudsen, 1997). However, FABP may bind
LCACoA esters with higher affinity than assumed in these calculations.
Therefore, it is likely that the free concentration of LCACoA is even lower
than described in Faergeman and Knudsen (1997).
LCACoA esters can also bind to a number of other proteins in the
cell including the high affinity binding site on acyl-CoA synthetase and acyl-
CoA utilizing enzymes. Webb
et al.
(1987) have identified an open reading
frame in a bovine brain cDNA library which encodes a 533 amino acid
protein containing an ACBP-like domain, termed bovine brain factor
(bBF). Based on the amino acid sequence, it was suggested that bBF could
be associated to either cell surface- or mitochondrial membrane (Todaro
et
al.
,
1991). It is tempting to speculate that membrane-associated bBF binds
fatty acyl-CoA with high affinity, and thus by competing with the cytosolic
ACBP is able to create a local pool of membrane bound acyl-CoA esters.
In addition, LCACoA esters readily partition into membranes. The associ-
ation constant of palmitoyl-CoA for the interaction with phospholipid
membranes
10
5
M-1
(Requero
et al.,
1995a; Peitzsch and McLaughlin, 1993). Applying these
values to
in vivo
conditions the calculated free concentration of acyl-CoA
in a liver cell in the absence of binding proteins would be about 1 µM The
in vivo
cytosolic concentration of LCACoA in a liver cell can therefore be
expected to be well below 0.2 µM and never exceed 1 µM
The size of the different acyl-CoA pools has also been postulated to
be regulated by acyl-CoA hydrolases (Berge and Aarsland, 1985). Acyl-
CoA hydrolases are found in most subcellular compartments and include
short-, medium-, and LCACoA hydrolases (Lindquist
et al.
,
1998; Svensson
et al.,
1998; Yamada
et al.,
1998; Engberg
et al.,
1997; Yamada
et al.,
1997;
Waku, 1992; Berge
et al.,
1984; Berge, 1979; Berge and Farstad, 1979). Acyl-
CoA hydrolases usually display K
m
values ranging from 0.1-6 µM for
LCACoA esters (Yamada
et al.,
1996; Broustas and Hajra, 1995; Berge,
1979). Some acyl-CoA hydrolases have been shown to respond to meta-
bolic stresses, i.e. increasing by ingestion of hypolipidemic drugs (Lindquist
et al.,
1998; Svensson
et al.,
1998; Yamada
et al.,
1998; Engberg
et al.,
1997;
Yamada
et al.,
1997), which also results in an increase in the total acyl-CoA
level in rat liver (Berge and Bakke, 1981). Moore
et al.
(1992) have shown
that acyl-CoA hydrolase activity in rat adipocytes was decreased upon star-
vation, while the acyl-CoA level increased. Whether the intracellular acyl-
CoA concentration is regulated by acyl-CoA hydrolase activity is not
known. Nevertheless, it is very likely that acyl-CoA hydrolases could act as
has
been
determined
to
be
approximately
1.5-5
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