Professional Documents
Culture Documents
SCHOOL OF MEDICINE
DEPARTMENT OF PHYSIOLOGICAL SCIENCES
BIOCHEMISTRY
GLUCONEOGENESIS
Mr Mwale Nicholas K.
Email: mwalenicholask@unza.zm/ mwalenicholask@yahoo.com
OBJECTIVES
Gluconeogenesis
Precursors of gluconeogenesis
Regulation of gluconeogenesis
RESOURCES
All images and notes are taken from the
following unless otherwise stated;
Nelson, D. L & Cox, M. M; Lehninger Principles
of Biochemistry Fifth Edition (2008). W.H.
Freeman & Co. Pp 551-558, 583-590.
Introduction
o Sugar- almost a universal energy source
Introduction cont.
Blood glucose and glycogen stores are easily
depleted after periods of fasting or vigorous
exercise.
During these periods, organisms (plants, animals
fungi and microorganisms) need to synthesize
glucose from NON CARBOHYDRATE sources.
GLUCONEOGENESIS
Important gluconeogenic precursors include;
Lactate
Pyruvate
Glycerol
Certain amino acids
Generally three and four carbon compounds
serve as precursors.
Gluconeogenesis in mammals occurs mainly in the
liver (to lesser extent in kidney and intestinal
wall cells).
GLUCONEOGENESIS cont
New glucose produced goes via blood to supply
tissues
Lactate from skeletal muscle goes via blood to
liver.
In liver this get converted back to glucose and in
muscle will be stored as glycogen.
This cycle is called the Cori Cycle.
Cori Cycle
Active muscles use up
glycogen for energy.
Lactate is generated
during anaerobic
respiration.
Lactate
liver
(generates glucose).
Glucose stored as
glycogen in muscle.
Gluconeogenesis cont.
Occurs in opposite direction to glycolysis (but steps
not completely identical).
7 of 10 reactions use the same enzymes but 3
reactions are irreversible (high negative free
energy change) in glycolysis and use unique enzymes
during the gluconeogenetic pathway;
1. Conversion of phosphoenolpyruvate to pyruvate
2. Conversion of Fructose-6-phosphate to
fructose 1,6-phosphate.
3. Conversion of Glucose to Glucose-6-phosphate
Opposing pathways
of glycolysis and
gluconeogenesis
Gluconeogenesis cont
Pyruvate
from
cytosol
is
transported
mitochondria.
Pyruvate can be obtained from alanine
transamination.
Alanine
to
by
Overview of gluconeogenesis
Gluconeogenesis is expensive but highly necessary
for maintenance of blood sugar.
Overall energy expenditure is;
Precursors of gluconeogenesis
4,5,6 carbon molecules from the citric acid cycle
can be oxidized to oxaloacetate.
Precursors of gluconeogenesis
cont
Carbon atoms of many amino acids can
be
catabolized to pyruvate or intermediates of the
citric acid cycle (which are then oxidized to
oxaloacetate).
Precursors of gluconeogenesis
cont..
Acetyl CoA from fatty acid catabolism
in
contrast does not serve as a precursor for
gluconeogenesis.
Amino acids, glycerol and other compounds that
can be catabolized into components for
gluconeogenesis are called glucogenic compounds.
REGULATION OF GLUCONEOGENESIS
Both
glycolysis
(sugar
breakdown)
and
gluconeogenesis (making sugar from non carb
sources) occur in cell cytosol.
Means these two processes are regulated in a
coordinated manner so when glycolysis is
favored, gluconeogenesis is hindered.
The three irreversible reactions serve as a
regulatory point.
Other substrates and by products such as ATP,
AMP, reaction intermediates have an effect on
the enzymes.
Hormones also regulate enzyme activity.
opposite)
Effects of F-2,6-BP on
glycolysis and gluconeogenesis
FBPase-2
PFK-2= Phosphofructokinase 2
FBPase = F-2,6 bisphosphatase
ACTIVATION/INACTIVATION OF ENZYMES BY
MODIFICATION OF RESIDUES
In muscle,
cAMP.
epinephrine
(adrenalin)
enhances
33