“Liver is a glucose source. Muscle is a glucose sink”. Discuss.

The transport of glucose around the body is vital to normal functioning as glucose is the
key metabolite of respiration, which is necessary for life. In animals, glucose is mainly
stored as glycogen. There needs to be regulation of glucose and glycogen proportions
according to the body’s needs. This essay will only be discussing skeletal muscle.

Glycogen is primarily stored in the liver but is also found in muscle cells. The
degradation of glycogen in each of the cell types differs based on the organs’ functions.
The liver is responsible for maintaining blood glucose concentration, and so conducts
glycogenolysis when the blood glucose concentration has dropped. It then follows that
hepatocytes respond to glucagon, which triggers glycogenolysis in order to raise the
blood glucose concentration. The glucose in the blood is then transported to other
organs which need it for respiration. Gluconeogenesis is another process occurring in
the liver that raises blood glucose concentration. This is essentially the reverse of
glycolysis; starting with pyruvate, it is combined with acetyl CoA to form oxaloacetate
which is then converted to glucose through a series of enzymatic reactions. Crucially,
muscles do not have the enzymes required for gluconeogenesis. Through these two
methods, the liver can be seen as a glucose source as it is producing glucose for other
parts of the body to use.

The purpose of glycogenolysis in muscle cells is to create a respiratory metabolite to

supply energy for muscle contraction. Glucose is not technically made in this process as
it is more energetically efficient to skip glucose in the degradation pathway. From
glycogen, glucose-1-phosphate and then glucose-6-phosphate is made. In the liver, this
would then be converted into glucose. This is not done in muscle cells as glucose-6-
phosphate can be inserted directly into glycolysis to create pyruvate and then acetyl
CoA. This produces 1 more ATP than glycolysis from glucose because there is no need
for the first step of glycolysis, which is the phosphorylation of glucose to form glucose-
1-phosphate using ATP. Because of this, during rapid muscle contraction, e.g. in exercise
or chasing prey, glycogenolysis is favoured. This regulation is done so by utilising the
influx of Ca²⁺ that comes with muscle contraction. Glycogen phosphorylase, which
catalyses glycogen breakdown, is activated by Ca²⁺.

Despite this, muscle cells still take up glucose from the blood. This is because the
glycogen stores in muscle cells are insufficient for the energy requirements of muscle
contraction. Additionally, muscle cells also have a role in maintaining blood glucose
concentration. The presence of insulin, which is released due to increasing glucose
levels, causes the insertion of GLUT4 proteins in the plasma membrane, allowing
muscle cells to take up glucose. Thus we see that muscle cells are a very important
glucose sink.

The regulation of blood glucose concentrations requires both release and uptake, and
so liver cells are capable of both. Liver cells also respond to insulin, except it triggers
glycogenesis. This process can begin with glucose that has been taken up by the liver
cells, or from pyruvate. The initial steps when starting with pyruvate are identical to
gluconeogenesis, except glucose-6-phosphate is converted to glucose-1-phosphate,
which is then added onto the end of a glycogen branch by glycogen synthase.
Hence the liver can act as both a glucose source and sink depending on the conditions of
the body. Muscle cells are always a glucose sink – although they also conduct
glycogenolysis, the product is used intrinsically and not transported out of the cells. The
liver and muscles work closely together, such as in the Cori cycle during anaerobic
respiration, where the liver carries out gluconeogenesis on the lactate produced by the
muscle through pyruvate.