Download Regulation on Cellular respiration

Regulation of Cellular respiration
and
Related pathways
Allosteric regulation:
Hexokinase is inhibited by
glucose-6-P. If glucose 6
phosphate accumulates
because the rate of glycolysis
is low, then hexokinase is
inhibited and the conversion
of glucose to G6P slows. This
is a very important regulatory
step, since it prevents the
consumption of too much
cellular ATP to form G6P
PFK is the ‘valve’
controlling the rate of
glycolysis.
-ATP inhibits the
phosphofructokinase reaction.
AMP activates the reaction.
Thus, when energy is required,
glycolysis is activated. When
energy is plentiful, the reaction
is slowed down.
• Phosphofructokinase is inhibited by
citrate. A large number of compounds—
for example, fatty acids and amino acids—
can be metabolized to TCA cycle
intermediates. High concentrations of
citrate indicate a plentiful supply of
intermediates for energy production;
therefore, high activity of the glycolytic
pathway is not required.
• This allows regulation between glycolysis
and the Kreb’s cycle.
-ATP
inhibits pyruvate
kinase; similar to the
inhibition of PFK.
-Pyruvate kinase is also
inhibited by acetylCoenzyme A.
-Fatty acids also
allosterically inhibit pyruvate
kinase, serving as an
indicator that alternative
energy sources are
available for the cell.
• Pyruvate kinase is also activated by
fructose-1,6-bisphosphate. This is an
example of feed-forward activation. If
glycolysis is activated, then the activity of
pyruvate kinase must also be increased in
order to allow overall carbon flow through
the pathway. Feed-forward activation
ensures that the enzymes act together.
Krebs cycle
Pyruvate oxidation
-Pyruvate dehydrogenase is allosterically
inhibited by NADH and activated by high
concentrations of NAD+.
-A high concentration of NADH in the cell
means that the Electron Transport Chain
is full of electrons and that ATP
production is high.
-Inhibition of this enzyme reduces the
amount of Acetyl Co-A that enters into
the Kreb’s cycle.
•
•
•
Citrate synthase is inhibited by ATP and
NADH.
Isocitrate dehydrogenase (ICDH)*:
allosterically activated by ADP and
NAD+; inhibited by ATP and NADH.
Also, citrate accumulation and transport
into the cytosol leads to activation of fatty
acid biosynthesis (storage of acetyl-CoA
as fat).
Metabolic
Pathways
 Glucose is not the only fuel on which cells
depend. Other carbohydrates, fats, even
proteins may in certain cells or at certain times
be used as a source of ATP.
 One of the great advantages of the step-by-step
oxidation of glucose into CO2 and H2O is that
several of the intermediate compounds formed
in the process link glucose metabolism to the
metabolism of other food molecules.
• Fats are stored in adipose tissue.
• When needed as an energy source, the fat
reserves are moved out of adipose tissue,
and broken down into glycerol and fatty
acids in the liver
• The glycerol portion of the molecule may be converted
into DHAP and then to G3P and enters the glycolytic
pathway.
• The glycerol may also be converted into glucose. This
process is called gluconeogenesis.
• Fatty acids are converted into molecules of acetyl-CoA ,
in a process called b-oxidation, and are oxidized in the
Kreb’s cycle of the mitochondria.
• B oxidation involves the successive removal
of two-carbon acetyl groups from the fatty
acid. Each cleavage requires one ATP, but
produces 1 NADH and 1 FADH2.
• The result is that Palmitic Acid, a 16-carbon
fatty acid, produces 131 ATP molecules,
whereas 2 glucose molecules produce 73
ATPs.
• By mass, lipids produce about twice the
energy yield of carbohydrates
• When fats are being used as the
primary energy source such as in
starvation, fasting or untreated
diabetes, an excess amount of acetyl
CoA is produced, and is converted into
acetone and ketone bodies. This
produces the sweet smell of acetone on
the breath, noticeable in a diabetic
state.
• The amino acids liberated by the hydrolysis of
proteins can also serve as fuel. First, the
nitrogen is removed, a process called
deamination. The remaining fragments then
enter the respiratory pathway at several points.
• For example: the amino acids Gly, Ser, Ala, and
Cys are converted into pyruvic acid and enter
the mitochondria to be respired.
• Acetyl-CoA and several intermediates in the
Kreb’s cycle serve as entry points for most of the
other amino acids.
• These links permit the respiration of excess fats and
proteins in the diet.
• No special mechanism of cellular respiration is needed
by those animals that depend largely on ingested fats
(e.g., many birds) or proteins (e.g., carnivores) for their
energy supply.
• Many of the points that connect carbohydrate
metabolism to the catabolism of fats and proteins serve
as two-way valves. They provide points of entry not only
for the catabolism (cellular respiration) of fatty acids,
glycerol, and amino acids, but for their synthesis
(anabolism) as well. Thus the catabolic breakdown of
starches can lead (through acetyl-CoA and PGAL) to the
synthesis of fat.