Glycogen is the polymeric of glucose. The reason this structure exists enables glucose to be stored in
the body. It is primary found in 2 stores within the body. These are the liver and skeletal muscle. 10%
of the livers weight is this glycogen. 1-2% of the muscle weight is glycogen. It is store in cytosolic
granules. It is an important store of energy in the body. In provide a quick source of energy for the
energy. This glycogen is a reservoir of energy, especially for neurons. Skeletal muscle glycogen can
be used for aerobic and anaerobic glycogen, this last one hour. When glucose levels within the
blood falls, glycogenolysis occurs to raise these glucose levels within the blood. Stored in the liver,
glycogen is found in a-1,4 glygocidic bond. This is the breakdown of glycogen, to glucose-1-
phosphate. This involves many enzymes, in particular glycogen phosphorylase, glycogen debranching
enzyme and phosphoglycomutase. Glycogen phospholoase, is a homodimeric enzyme subject to
allosteric control. Peridoxal phosphatase serves as a prosthetic group for glycogen phosphorylase.
its role is to break down the a-1,4 bonds from the non-reducing end, separating the chained
clycogen into separate glucose residues, until it reaches 4 away from a 1,6 glycocidic bond. This is
known as the branched portion of glycogen. Glycogen disbranching enzyme results in transferase
activity, that is transferring 3 glucose residues to the lower chain enabling glycogen phosphorylase
to act. Glycogen debranching enzyme then breaks this a-1,6 bond, freeing the last glucose molecule.
Glycogen phosphorylase continues its action. Phosphoglycomutase then acts to convert a glucose-1-
phospate into a glucose-6-phosphate, found in the lumen of the liver and kidney. This can enter the
glycolytic pathway and glycolysis. This is particularly active in skeletal muscle, supports muscle
contraction. However, in the liver, glucose is released in the blood. This enables the use of glucose-6-
phosphatase. Normal blood glucose levels range between 60-90mg/100ml, in cases where blood
glucose drops, this enzyme is required. It converts glucose-6-phostapte into glucose.
In the liver it is converted to glucose, by phosphoglycomutase. It is the main source of energy for the
brain and red blood cells. In the muscle in undergoes glycolysis/cac and etc or is stored as glycogen.
The Cori Cycle:
There is no glucose-6-pohsphatase present in skeletal muscle. ATP is produced by glycolysis (g-1-p
converted by phosphoglycomutase into g-6-p which enters glycolysis in the muscle) in this process
glycogen is converted into lactate and ATP for rapid contraction. In the skeletal muscle from glucose
to pyruvate to lactate. Pyruvate to lactate via lactate dehydrogenase, (NADH2 – NAD)
In the liver: lactate to pyruvate to glucose (lactate to pyruvate by ldh)
Also alanine cycle from pyruvate by gluatamate (alanine transferase) results with alpha
ketoglutarate & alanine, opposite in the liver.
Amino acid metabolism in the liver
This is the process of deamination and transamination of amino acids, followed by the conversion of
the non-nitrogenous parts of those molecules to glucose or lipids. Enzymes include alanine,
Transport across membranes:
plasma membrane – cytosolic different to extracellular side.
Glycolipids found on the outside of the cell
Mechanisims: osmosis, facilitated transport (down a concretion gradient via a specific transporter), active transport (against concentration gradient, through a specific transporter)
facilitated: glucose trasporter: GLUT1-5
Taken into the cell when glucose concentration manner. Intake into brain and rbc = insulin
independent. Muscle and adipose tissue, insulin dependent.
Different glucose transporter isoforms with variability in their kinetics and mechanisms of action
respond to the physiological demands of the body and maintain glucose levels within 4-5mM
Liver and pancreas GLUT2:
high km for glucose. Therefore when glucose levels within the blood is high, maximal uptake is
possible. In pancreatic beta cells, glucose uptake signals that blood glucose is high, this responds
with secretion of insulin.
When insulin reacts with its receptor, vesicles move to the surface and fuse with the plasma
membrane increasing no of glucose transporters in the plasma membrane. When glucose levels drop
transporters are removed from the membrane by forming small vesicles. Insulin stimulates glut4
expression on myocytes (synthesising glycogen) and adipocytes (synthesising triacylglycerols). This
results in an increase of glucose uptake by 15x or more. Type 1 diabetes, no insulin production, no
mobilisation of glut4, high blood glucose.
Regulation of Glucose metabolism:
After a meal, the liver converts glucose absorbed from the blood into glycogen. Between meals
the liver converts glycogen into glucose (glycogenolysis) to maintain a constant blood glucose
concentration. How are these two processes regulated? This is done via a process called
gluconeogenesis, which runs in parallel with glycolysis.
Strategies for metabolic control
Why does the body need to regulate pathways, how does the body regulate pathaways.
1. Regulation of enzyme concentration
2. Regulation of enzyme activity
Regulation of enzyme concentration (slow) , regulation of enzyme activity (fast)
regulation of enzyme concentration in cells and is role in the regulation of cellular metabolism.
Enzymes act as catalysts for chemical reactions within an organisms body, thereby dictating the
metabolism of an organism. Metabolic regulation is achieved through 2 controls. These are the
regulation of enzyme concentration, a slow way to increase or decrease action, or actual control of
the enzymes ability for action. This is modulated in two ways, inhibition and stimulation of classical
enzymes or modulation of an enzymes active site. This is achieved either be allosteric modulation of
activity, or covalent modulation of enzymes.
Certain enzymes are not expressed in certain tissues, therefore limiting the movement of various
substances in and out of a cell. For example skeletal muscle do not contain glucose-6-phosphotae,
and therefore glucose cannot exit the muscle. Concentration of certain enzymes are required to be
maintained at constant levels within some tissues to ensure continual function. Mitochondrial
enzymes use oxygen to enable constant production of ATP by mitochondria. These enzymes are termed constitutive proteins. The expression of enzymes that are needed under only specific
physiological states are regulated by the modulation of their synthesis. In times of need, enzyme
concentration can be increased via various cell signals that usually result in gene translation and
enzymatic production. Reducible enzymes are termed, due to repression of synthesis, most likely by
the end product of a metabolic pathway. In this situation, the product that relied on the enzyme to
be produced is not found in high concentrations, causing negative feedback on the enzyme action.
kinetic regulation of enzyme activity
Enzyme Kinetics is the rate at which enzymes act of their substrate to produce a reaction,
Modulation of this results in the regulation of enzyme activity. Classical Michaelis-Menten Kinetics
displays a hyperbola rate of enzyme reaction. It shows enzyme rate is proportional to the
concentration of substrates, however when enzyme activity approaches a limiting rate when s
substrate levels continual increase. This shows that under constant ezyme levels, enzymatic rection
increases, but will reach a maximum rate of reaction, regardless if substrate levels continue to
increase. Glucokinase is an enzyme that facilitates the conversion of glucose to g-6-p. It acts as a
glucose sensor, responding to falling or increasing glucose levels. Glucokinase (liver) had a stong
affity for glucose of 12mM and hexokinase (Glucokinase 1) has a lower affinity 0.04mM.
Activity of Glucokinase facilitates the conversion of glucose to g-6-p. Within skeletal muscle,
catalysis of the reaction occurs efficiently under normal conditions. It acts in combination with
GLUT4 to maintain a balance between glucose uptake and glucose phosphorylation. It is also
allosterically inhibited by g6p in order to prevent build up of gp6 within a cell. Km refers to the
substrate concentration at 50% of enzyme activity. Km of hexokinase 1 = 0.04M.
Within the liver however, hexokinase IV has a km of 10mM. Therefore it will only phosphorylate
glucose when levels are high, providing g6p for glycogen synthesis. It acts in combination with
GLUT2. Glucokinase and glut2 allow intracellular g6p to equal blood glucose concentrations of 5mM,
enabling beta cells to respond to elevated blood glucose levels. It is not inhibited be g6p
allosterically but by other intermediate metabolites. Therefore after ingestion of carbohydrates,
there is an increase of Glucokinase activity and reduction of g6phosotase, favouring g6p production.
When blood concentration is 5mM there the no ne flux