While on a fasted state, the organs and tissues are on a high necessity for energy. In this
scenario the liver will go through the steps of glycogenolysis. There is a non-reducing
end at every end of every branch in glycogen and this sugar along with the others in its
chain are connected through a 1-4 glycosidic bond. This bond is then sequentially cleaved
by glycogen phosphorylase, and that is going to add an inorganic phosphate at the end of
the alpha 1-4 position. To make glucose 1-phosphate. This enzyme cannot cleave past
that alpha 1-6 branch point. An enzyme known as Glucan Transferase will remove three
glucose residues from the non-reducing end of a branch and it is going to transfer them to
another nearby non-reducing end. This is going to leave one glucose remaining from the
original branch and that’s going to be connected through a 1-6 glycosidic bond. The
single glucose 1-6 bond is going to be hydrolyzed by the alpha 1-6 glucosidase activity of
the debranching enzyme. Glycogen phosphorylases are going to keep on cleaving
individual non-reducing glucoses from other branches. They reduce to four glucoses of
the branching point and this will trigger transferase activity. The individual glucoses can
undergo isomerization, which transfers it from a glucose-1-phosphate to a glucose-6-
phosphate allowing these molecules to now enter into glycolysis. Glycolysis, a series of
enzymatic actions, Takes glucose and breaks it down to NADH and ATP. Can be
considered an anaerobic cytoplasmic pathway organized into three phases. Investment,
cleavage and energy harvest. Invest two ATPs, which act as an activation energy yield.
Enzymes take phosphates from ATPs, moving them to glucose and causing a fructose
rearrangement (This leaves Fructose 1-6 bisphosphate along with two phosphates, which
makes it highly unstable). Then we have the cleaving of fructose bisphosphate. Cleaving
leaves two Glyceraldehyde 3-phosphate, G3P. During energy harvest, G3P is rearranged
and oxidized by an enzymatic assembly line that harvests energy from each G3P. One
NADH and two ATPs double this yield per G3P to two NADH and four ATPs. Two
ATPs were invested in phase one so you net just two. Put two in get four as a result for a
net gain of two ATPs. Pyruvate has different fates depending on the metabolic pathway it
is sent to. If it is anaerobic, it will be fermented. In aerobic cells, pyruvate’s termination
will be the Krebs cycle and total oxidation. Glycolysis will work most optimally on a fed
state preferably with a good consumption of carbohydrates. During gluconeogenesis, we
make new glucose and it is the reserve of glycolysis. An amino acid can convert to
pyruvate to initiate gluconeogenesis. Glycerol from fat tissues such as adipose tissues can
also be a source for gluconeogenesis. Starting with the conversion of
phosphoenolpyruvate to pyruvate by pyruvate kinase. To yield PEP from pyruvate from
gluconeogenesis we need enzymes pyruvate carboxylase, and PEP carboxykinase.
Pyruvate carboxylase carboxylates pyruvate in the mitochondria to form oxaloacetate.
Oxaloacetate, a TCA cycle intermediate cannot pass through the mitochondrial
membrane into the cytoplasm. It is reduced to malate, which leaves the mitochondria
through the malate shuttle, and enters the cytoplasm, where it becomes reoxidized back to
oxaloacetate. Oxaloacetate is then decarboxylated and phosphorylated by PEP carboxyl
kinase to form PEP. PEP is then acted on by the reactions of glycolysis going in the
opposite direction until it becomes fructose 1,6-biphosphate. Then we have the
phosphorylation of fructose-6-phosphate into fructose-1,6-bisphosphate. We are just
adding another phosphate to the molecule. It is good to note that this is an irreversible
step catalyzed by the enzyme phosphofructosekinase-1 in glycolysis. In gluconeogenesis,
phosphofructokinase 1 (PKF1) is replaced by fructose 1,6-bisphosphatase. This will
hydrolyze fructose 1,6-bisphosphate to form fructose-6-phosphate. Which is then
converted to glucose-6-phosphate. Glucose 6-phosphatase replaces hexokinase. Glucose
6-phosphate is transported from the cytosol into the endoplasmic reticulum, where it is
hydrolyzed by glucose-6-phosphatase to create free glucose. This free glucose will re-
enter the cytosol from which it leaves the cell. Glucose-6-phosphatase is a hepatic
enzyme, meaning you can only really find it in the liver. The absence of this enzyme
from skeletal muscle accounts for the fact that muscle glycogen cannot serve as a source
of blood glucose. It is also important to note that once the liver forms glucose through
gluconeogenesis, this cannot really be used as an energy source for the liver.