CMLS, Cell. Mol. Life Sci. 57 (2000) 1360–1372
1420-682X/00/101360-13 $ 1.50+0.20/0
© Birkha¨user Verlag, Basel, 2000
Cellular uptake of long-chain fatty acids: role of
membrane-associated fatty-acid-binding/transport proteins
A. K. Dutta-Roy
Rowett Research Institute, Aberdeen AB21 9SB, Scotland (United Kingdom), Fax +44 1224 716629,
e-mail: adr@rri.sari.ac.uk
Abstract. The critical importance of long-chain fatty hexaenoic acids across the placenta is of critical impor-
acids in cellular homeostasis demands an efficient up- tance for fetal growth and development. Our studies
have shown that arachidonic and docosahexaenoictake system for these fatty acids and their metabolism
acids are preferentially taken up by placental tro-in tissues. Increasing evidence suggests that the plasma-
membrane-associated and cytoplasmic fatty-acid-bind- phoblasts for fetal transport. The existence of a fatty-
acid-transport system comprising multiple membrane-ing proteins are involved in cellular fatty acid uptake,
binding proteins (FAT, FATP and FABP
pm
) in humantransport and metabolism in tissues. These binding
placenta may be essential to facilitate the preferentialproteins may also function in the fine tuning of cellular
events by modulating the metabolism of long-chain transport of maternal plasma fatty acids in order to
fatty acids implicated in the regulation of cell growth meet the requirements of the growing fetus. The prefer-
ential uptake of arachidonic and docosahexaenoic acidsand various cellular functions. Several membrane-asso-
ciated fatty-acid-binding/transport proteins such as by the human placenta has the net effect of shunting
these maternal plasma fatty acids towards the fetus.plasma membrane fatty-acid-binding protein (FABP
pm
,
43 kDa), fatty acid translocase (FAT, 88 kDa) and The roles of plasma membrane-associated binding/
fatty acid transporter protein (FATP, 63 kDa) have transport proteins (FABP
pm
, FAT and FATP) in tis-
sue-specific fatty acid uptake and metabolism arebeen identified. In the feto-placental unit, preferential
transport of maternal plasma arachidonic and docosa- discussed.
Key words. Plasma membrane fatty-acid-binding protein (FABP
pm
); fatty acid translocase (FAT); fatty acid
transporter protein (FATP); free fatty acid (FFA); fatty acid uptake; long-chain polyunsaturated fatty acids
(LCPUFAs); long-chain fatty acids (LCFAs).
Introduction
Long-chain fatty acids (LCFAs) play important roles in
cell homeostasis [1 –4]. Fatty acids serve as a metabolic
energy source, building blocks for membrane lipids and
cellular signalling molecules such as eicosanoids [2–6].
In addition, fatty acids may directly or indirectly inter-
act with membranes, transporters, ion channels, en-
zymes or hormone receptors and thus regulate various
cell functions [2–6]. Essential fatty acids (EFAs) and
their long-chain polyunsaturated fatty acid (LCPUFA)
derivatives are of critical importance in cell growth and
development [2–6]. They are also increasingly being
recognised as important intracellular mediators of gene
expression [7]. Because of the fundamental role of EFA
and LCPUFA as structural elements and functional
modulators, it has been hypothesised that the EFA/
LCPUFA status of tissue or cells is an important deter-
minant of health and disease [2 –6]. The multiple roles
of fatty acids suggest that careful regulation of all
aspects of their disposition, including cellular uptake
and subsequent intracellular transport, are critical for
the maintenance of cellular integrity. However, the very
property that makes LCFAs well suited to be compo-
nents of membranes, i.e. their acyl chain hydrophobic-
ity, complicates the process of transporting them from
sites of intestinal absorption, hepatic synthesis and
lipolysis to sites of utilisation. The insolubility of fatty
acids in the aqueous environment requires specific