Lecture 9 - Glucose Metabolism

Question 1

Describe the main fule sources in animal cells.

Answer 1

Most cells can derive energy from three fuel sources: Carbohydrates, amino acids and fatty acids
The major source of energy are the fatty acids which are degraded in the mitochondria to acetyl-CoA which then enters the citric acid cycle. Cells that don’t have mitochondria such as red blood cells or have relatively few such as the skeletal muscle either cannot or have a reduced ability to use fatty acids as fuels. These cells rely on glucose as their source of energy.
(The brain relies solely on glucose as its source of energy as fatty acids cant cross the blood brain barrier)

Question 2

Describe the digestion of dietry carbon.

Answer 2

Appx. 300g of carbohydrate is consumed per day, 20g of this are cellulase which aren’t digested as we don’t have the correct enzymes. Most is starch which consists of a mixture of amylose (linear chains 1,4 glycosidic bond) and amylopectin (branched wit 1,4 and 1,6 glycosidic bonds).
* Digestion begins in the mouth with salivary amylase
* Pancreatic juice contains two α-amylases
The absorbative cells of the intestinal villi secrete several CHO-degrading enzymes

Question 3

Describe the absorption of dietary carbon.

Answer 3

The monosaccharides are absorbed into the body by the enterocytes (absorbative cells) of the intestinal mucosa. The monosaccharides are transported across the lipid bilayer by specific transport proteins.
* Glucose is co-transported along with Na+ through SGLT1
* The concentration gradient of sodium is maintained by the Na+/K+ pump which maintains a low Na+ conc in the cytoplasm of absorptive cells.
Fructose is transported By the GLUT-5 into the cell and is transported out by GLUT 2 into the blood down its concentration gradient.

Question 4

Describe the role of the liver in glucose metabolism.

Answer 4

Absorbed sugars are passed to the capillaries of the villi and eventually join the bloodstream in the hepatic portal vein which leads to the liver.
Glucose uptake into the liver cells (hepatocytes) is facilitated by GLUT2 and is determined by the relative concentrations inside and outside the cells.
Within the hepatocyte glucose is phosphorylated by glucokinase which effectively traps the glucose inside the cell. It can then be stored (as glycogen) or metabolised to produce ATP (by glycolysis)

Question 5

How does glucose phosphorylation occour and why is it important?

Answer 5

Glucose is phosphorylated to form glucose-6-phophate for two reasons:
1. To prevent it from passing out of the cell
2. To prepare it for storage by glycogenesis or breakdown by glycolysis

Glucose is converted to glucose-6-phosphate by two different isoenzymes glucokinase and hexokinase which means it can’t be transported by GLUT.
* Glucokinase activity is tightly regulated and is only found in the liver. It has a low affinity but a high capacity so it can work quickly if the glucose concentration is high. Takes up more at high glucose concentrations so can take up excess.
* Hexokinase is not found in the liver but instead in muscle and other tissues. It has a high affinity so takes up glucose at low concentrations providing for the immediate requirement.
Isoenzymes are enzymes that catalyse the same chemical reaction but display different chemical and physical properties.

Regulation method 1
Enzyme kinetics/isoenzymes -the enzymes are regulated by enzyme kinetics

Question 6

What is the average glucose repquirement for humans

Answer 6

• About 12g of free glucose are present in blood and tissue fluid
  
  • The brain needs about 5-6g of glucose per hour (over 70% of total glucose usage by the body)
    Therefore, our circulating glucose would support us for about 2 hours if it wasn’t continually replaced from the glycogen and the diet.

Question 7

What is glycogenesis

Answer 7

Glycogen is composed of chains with alpha-1-4-glucosidic bonds (with alpha-1-6 branches). It has a protein core (glycogenin) which forms the start of the glycogen molecule.
Glycogen is highly branched and has a helical structure and is semi-soluble
* It is synthesised from glucose-6-phosphate
* It is stored within tissues as glycogen granules
It can be rapidly broken down to give glucose-6-phosphate

Glycogen synthesis:

1. Glucose 6-phosphate has the phosphate group moved to Glucose 1-phophate by phosphoglucomutase 
2. Glucose 1-phosphate and UTP react to form UDP glucose and 2Pi. The reaction is catalysed by UDP-glucose pyrophosphorylase
3. The high energy bond between the phosphates and the glucose is broken and glucose is then added to a glycogen chain. The reaction is catalysed by glycogen synthase
4. Branching is catalysed by amylo(1,4-->1,6)transglycosylase "the branching enzyme" A 7 glucose unit is removed and transferred to form a 1,6 bon in a position further down the chain.