The evil villain Dr Gruose has developed a toxin that target

The evil villain, Dr. Gruose, has developed a toxin that targets carbohydrate transporters. However, there are 5 carbohydrate transporters and his toxin only targets GLUT 4.

1- Explain whether or not this toxin would be devastating to human targets?

2- Would GLUT 5 been a better target?

3- How about GLUT 1?

Solution

1- Yes this toxin will be devastating for the human targets as it targets the Glucose transporter type 4 (GLUT-4).

Glucose transporter type 4 also known as GLUT-4 is a very important insulin-regulated glucose transporter. It is found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle). It has high affinity for Glucose and is also responsible for insulin-regulated glucose storage.

GLUT4 present at cell surface, allows the facilitated diffusion of circulating glucose down its concentration gradient into muscle and fat cells. Glucose is then rapidly phosphorylated by glucokinase in the liver and hexokinase in other tissues to form glucose-6-phosphate, which in turn enters glycolysis or is converted to glycogen. Glucose-6-phosphate cannot diffuse back out of cells, which also serves to maintain the concentration gradient for glucose to passively enter cells

The binding of the toxin can thus result in impairment in insulin-stimulated trafficking of GLUT4 in the hippocampus leading to decreased metabolic activities and plasticity of hippocampal neurons, which further results in depressive like behavior and cognitive dysfunctioning.

2- No, GLUT 5 will not be a better target, as the toxin targets the transporter specific to Glucose, whereas GLUT 5 is a fructose transporter. GLUT 5 is expressed on apical border of enterocytes in the small intestine.

3- GLUT 1 can be potential target as it also transports glucose (high affinity) across the plasma membrane and galactose, not fructose. The major site of expression for GLUT 1 includes brain, endothelial cells , fetal tissues and highest level of expression is found in erythrocytes. Glucose enters the erythrocytes by facilitated diffusion through GLUT 1. The expression of GLUT1 in cell membrane is increased by reduced glucose level and vice versa.