Transcript Adenylate Energy Charge

Adenylate Energy Charge
Some enzymes respond to absolute
concentration, but most respond to ratios.
Dan Atkinson introduced the concept of
ENERGY CHARGE in 1968 to summarize
the energy status of a cell.
It is a measure of the relative concentration of
high-energy phospho - anhydride bonds
available
in
the
adenylate
pool .
The adenylate energy charge, or AEC, has the
range 0 to 1.0. If all the adenylate is in the form of
ATP, AEC = 1.0, and the potential for phosphoryl
transfer is maximal.
At the other extreme, if AMP is the only adenylate
form present, AEC = 0.
Then the relative amounts of the three adenine
nucleotides are fixed by the energy charge. The
following figure shows the relative changes in the
concentrations of the adenylates as energy charge
varies from 0 to 1.0.
Regulatory enzymes in energy-producing
catabolic pathways show greater activity at
low energy charge, but the activity falls off
sharbly as AEC approaches 1.0.
In contrast, regulatory enzymes of anabolic
sequences are not very active at low energy
charge, but their activities increase as AEC
nears 1.0 .
These contrasting responses are termed R, for
ATP-regenerating, and U, for ATP-utilizing.
Regulatory enzymes such as PFK and
pyrvuate kinase in glycolysis follow the R
response curve as AEC is varied.
Note that PFK itself is an ATP-utilizing
enzyme, using ATP to phosphorylate fructose6-phosphate
to
yield
fructose-1,6bisphosphate. Nevertheless, because PFK acts
physiologically as the valve controlling the
flux of carbohydrate down the catabolic
pathways of cellular respiration that lead to
ATP regeneration, it responds as an “R”
Regulatory enzymes
in anabolic
pathways,
such
as
acetyl-CoA
carboxylase, which initiates fatty acid
biosynthesis, respond as “U” enzymes.
Cellular energy homoeostasis: maintenance of
energy state by creatine kinase (CK) and
adenylate kinase (AK) isoenzymes
A fundamental principle in multicellular
organisms is the strict maintenance of
stable concentrations of intracellular
oxygen and ATP as the universal energy
currency of biological systems, as well as
the tight regulation of energy utilization
with energy supply.
Upon activation of excitable cells, such as skeletal
and cardiac muscle, or brain and nerve cells, ATP
turnover rates may increase by several orders of
magnitude within seconds, but [ATP] remains
remarkably stable and ATP/ADP ratios, as well as
ATP/AMP ratios, are maintained as high as possible
to guarantee optimal efficiency for cellular ATPases
that are at work to perform a multitude of energydependent cellular activities, such as muscle
contraction, cell motility and ion pumping.
concerted action of kinases involved in
energy homoeostasis
ATP homoeostasis and maintenance of high
ATP/ADP and ATP/AMP ratios are facilitated by
the action of two well-known enzyme systems,
working as very fast and efficient energy
safeguards. First, CKs, efficiently regenerating
ATP at the expense of phosphocreatine (PCr)
by the following reaction.
PCr+ADP
ATP+Cr
Second,
Adenylate
kinase
(AK),
reconverting two ADP molecules into one
ATP and one AMP.
These two enzymes, working together in
an subcellular energy distribution network
or circuit temporally and, due to their
subcellular microcompartmentation, to
buffer subcellular ATP level.
A common cause of many diseases, like
cardiac insufficiency, cardiac hypertrophy as
well as most of the neurodegenerative
pathologies, is a generally lowered cellular
PCr/ATP ratio, indicating a lowered energy
state of cells and tissues.
This is often accompanied by elevated calcium
levels, leading to chronic calcium overload with
its host of negative consequences on cell
function and viability.