I'd like to bring the following article to your attention.
I like the "pure scottish wool (/scotch whisky?)" style...
I'm confident you will find a way to use it in Biochem/Physiol classes.
Claude
Claude Aflalo ########################## Phones: Office 972-7-6472118 ####
Unit for Science Teaching/Dept. of Life Sciences Lab 972-7-6472119
Ben Gurion University of the Negev Fax 972-7-6472890
P.O.Box 653 email: aflaloc at bgumail.bgu.ac.il
Beer Sheva 84105 Israel ### URL: http://www.bgu.ac.il/~aflaloc/aflalo.html
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J Physiol 2000 Oct 1;528(Pt 1):3
How to avoid running on empty.
Rennie MJ
Department of Anatomy and Physiology, University of Dundee, Dundee DD1
4HN, UK.
Energy production by skeletal muscle shows a range of output which is
unmatched by any other tissue. At rest, muscle oxygen consumption trickles
along at about 2 ml kg-1 min-1 using mainly fatty acids and a little bit
of carbohydrate, processed to lactate only. However, when the system is
activated (for example in a 5000 m runner), working muscle oxygen
consumption may be nearly 200-fold more. If ATP were not resynthesized
after its use by myosin ATPase a marathon runner would need over 20 kg to
finish! Even this power output is not maximal: the ultimate rate of ATP
utilization occurs during jumping and throwing events and it may be many
times higher than during maximal aerobic work.
In mechanical engines a single type of fuel (gas, diesel oil, petrol,
electricity) is used at all power outputs but in muscle a number of
different types of fuel are used (e.g. creatine phosphate, glucose,
glycogen, lactate, ketone bodies, free fatty acids and triglycerides) as
appropriate to the task. Some fuels are stored in muscle and some are
imported via the blood. Some are catabolized to produce ATP without the
involvement of oxygen and some are fully oxidized to CO2 and water. By and
large the processes which have the highest power output rely on fuels
stored in very small amounts (e.g. creatine phosphate) and those which
have the highest capacity (e.g. ATP production from fatty acid oxidation)
can sustain only moderate power outputs.
How all this is integrated and controlled remains a major mystery
but recent rapid advances in the field are allowing us to perceive the
outlines of some general control mechanisms. The linchpin appears to be a
protein kinase which is activated by adenosine monophosphate (AMP).
AMP-activated protein kinase (AMPK) was discovered by Graham Hardie's
group when working on the phosphorylation and inactivation of enzymes of
lipid metabolism (Carling et al. 1987). It has now been recognized that
AMPK phosphorylates enzymes in a wide range of other metabolic pathways
which show acute and chronic adaptation to various forms of cellular
stress including heat shock, contractile activity and nutrient
deprivation. Indeed, Hardie has christened the phosphorylation cascade
involving AMPK 'the cellular fuel gauge', conceiving it as monitoring the
energy status of the cell (Fig. 1). AMPK is allosterically activated by
5'-AMP which promotes its phosphorylation by an upstream kinase (AMPKK)
and inhibits its dephosphorylation. Because of the reaction of adenylate
kinase (2ADP ATP + AMP) the change in AMP concentration as a result of the
utilization of ATP is amplified, making the AMP concentration an acutely
sensitive indicator of the rate of ATP utilization (Hardie & Carling,
1997). The creatine kinase enzyme, which buffers sarcoplasmic ATP
concentrations during contractile activity, is phosphorylated in muscle
cells by AMPK, a change which is stimulated by creatine and low pH and
inhibited by phosphocreatine (Ponticos et al. 1998) - all characteristics
which would stimulate AMPK activity during muscular contraction.
Will Winder and his colleagues from Brigham Young University have been
very active in demonstrating the possible involvement of AMPK in the
regulation of muscle metabolism during exercise. They showed that in
electrically stimulated rat muscle and in running rats, AMPK was activated
with appropriate catabolic effects such as activation of fatty acid
oxidation (Rasmussen & Winder, 1997). The effect appeared to be dependent
upon exercise intensity and to occur mainly in red, rather than white,
muscle. The catalogue of metabolic processes involving activation of
5'-AMP is now said to include increases in the concentration of glycogen,
the glucose transporter GLUT4, hexokinase, and of mitochondrial enzymes in
skeletal muscle (Holmes et al. 1999; Winder et al. 2000). Until very
recently, all of the available information has come from work in non-human
tissues. It is therefore somewhat of a relief (as well as being a
harbinger of a likely flood of new work) to see that the phenomenon also
occurs in human muscle. Two groups have independently obtained almost
identical results showing this. Fujii and colleagues (Fujii et al. 2000)
of the Joslin Diabetes Center, Harvard Medical School, and Wojtaszewski
and co-workers from the Copenhagen Muscle Research Centre (this issue of
The Journal of Physiology) showed, by analysing AMPK activity in biopsies
from vastus lateralis muscle obtained before and immediately after bicycle
exercise (at 70% VO2, max for 20-60 min) that there was a substantial
covalent activation of the alpha2-subunit of AMPK. Exercise at a lower
intensity for a longer period did not activate the enzyme although the
stimulation was greater after 60 min of exercise than after 20 min
(Wojtaszewski et al. 2000; Fujii et al. 2000). Both groups showed that the
alpha1-subunit was never activated, but that the activation of the
alpha2-subunit persisted for at least 30 min post-exercise. These papers
document the logical next step in transferring the investigation of AMPK
into human physiology. I predict that this work will have an important
heuristic effect. It should stimulate physiologists to investigate the
role of AMPK in the control of many phenomena associated with muscle
metabolism and contractile activity, including the relationship between
fatty acid and glucose oxidation, the expression of particular genes
associated with specific modes of contractile activity and the utilization
of phosphocreatine during high intensity exercise.
However, one phenomenon which may not be associated (somewhat
surprisingly) with AMP activation is the stimulation of glucose transport
observed in rat skeletal muscle during electrically stimulated contraction
(Derave et al. 2000). But there again, the definitive experiment has not
been done - in human muscle!
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