Download Regulation of fatty acid synthesis and degradation by the AMP

A I02
Biochemical Society Transactions (2002) Volume 30, Part 6
B6 Regulation of fatty acid synthesis and degradation by the
88 Altering specificity of a Ricinus communis cytochrome b5
AMP-activated Drotein kinase
fusion desaturase
L.V. Michaelson and J.A. Napier
IACR-Long Ashton Research Station, Long Ashton, Bristol,
BS41 9AE UK.
D.G. Hardie
Division of Molecular Physiology, School of Life Sciences,
Wellcome Trust Biocentre, University of Dundee, DOWStreet,
Dundee, DD1 JEH, Scotland, UK
The AMP-activated protein kinase (AMPK) is the downstream
component of a kinase cascade that is activated by rising AMP and
falling ATP, which together signal a fall in cellular energy status.
Although it probably has many targets, two key targets are acetylCoA carboxylase-1 and -2 (ACCI and ACCZ), both of which are
inactivated by AMPK. A C C l catalyzes the key regulated step in
fatty acid synthesis in liver and other tissues. ACCZ, which is
expressed at high levels in skeletal and cardiac muscle, appears not
to be involved in fatty acid synthesis but instead produces malonylCoA that regulates fat oxidation by inhibiting fatty acid entry into
mitochondria. AMPK is activated by contraction in skeletal muscle
and is responsible, at least in part, for the increased glucose uptake
and fat oxidation that occurs during endurance exercise. AMPK
also regulates gene expression, and inhibits the expression of A C C l
and fatty acid synthase in liver, while stimulating expression of
mitochondria1 oxidative enzymes in muscle. AMPK is also activated
in muscle by leptin, a signal signifying abundant fat depots. In
terms of fat metabolism, activation of AMPK switches the body
from anabolic to catabolic mode. The AMPK system is activated by
two of the three major classes of drugs used to treat Type 2 diabetes
(biguanides and thiazolidine diones), and may be responsible for the
lipid lowering effects of these agents.
87 Transcription factors acting on the promoter of the fatty acid
synthase gene.
M. Schweizer, K. Roderl, L. Zhang, S.S. Wolf2
Department of Biological Sciences, Heriot- Watt University,
Edinburgh, UK; IDepartment of Nutritional Sciences,
University of California, Berkeley; 2Jenapharm, Germany
Please refer t o abstract number 20. This abstract was originally
submitted as a poster, and on the basis of its scientific interest and
merit, was chosen by the colloquium organizers to be presented as
an oral communication, as well as a poster.
0 2002 Biochemical Society
Please refer to abstract number 24. This abstract was originally
submitted as a poster, and on the basis of its scientific interest and
merit, was chosen by the colloquium organizers to be presented as
an oral communication, as well as a poster.
B9
Gene regulation of mammalian desaturases
M.T. Nakamura
University of Illinois, FSHN, 905 S.Goodwin Ave, Urbana,
I L 61801, USA
Highly unsaturated fatty acids (HUFA) such as arachidonic acid
(20:4 n-6) and docosahexaenoic acid (22:6 n-3) are essential for a
variety of physiological functions including eicosanoid signaling,
pinocytosis, ion channel modulation, and gene regulation. Mammals
are capable of synthesizing HUFA from precursor fatty acids.
Delta-6 desaturase (D6D) and delta-5 desaturase (D5D) are the key
enzymes for this endogenous synthesis of both n-6 and n-3 HUFA.
The mRNA of D 6 D and D 5 D were expressed in many extrahepatic
tissues, suggesting an active synthesis of HUFA in multiple organs.
In liver, activities of both D6D and D 5 D are increased by insulin,
growth hormone and peroxisome proliferators (PP), whereas dietary
polyunsaturated fatty acids (PUFA) decrease the activities. D 6 D
activity is largely regulated at the transcriptional level. O n e of the
key regulators is sterol regulatory element binding protein-lc,
which, at least in part, mediates transcriptional activation by insulin
and inhibition by PUFA. PP strongly activate transcription of the
D 6 D gene. However, it is yet to be determined whether peroxisome
proliferator activated receptor-alpha directly mediates the process.
Alternatively, PP may induce D 6 D by increasing oxidation and/or
demand of HUFA through proliferation of peroxisomes. Stearoyl
CoA desaturase (SCD), another well-characterized mammalian
desaturase, catalyzes the synthesis of non-essential, monounsaturated fatty acids. SCD is also regulated at the transcriptional level,
induced by insulin and PP, and suppressed by PUFA in liver. These
regulations of SCD are similar to those of D 6 D and D5D although
SCD is considered as a lipogenic enzyme and has apparently a
different physiological role.