Glycolysis Regulation

Red blood cells

1. Rely solely on glycolysis to produce ATP

2. Approximately 25% of glucose in RBCs is used to produce the RBC specific metabolite 2,3-bisphosphoglycerate for haemoglobin O2 affinity modulation

3. RBCs depend on the oxidative branch of Pentose phosphate pathway (ppp) to generate reducing equivalents (NADPH) to preserve glutathione homeostasis and counteract oxidative stress

2,3-bisphosphoglycerate

An allosteric effector that promotes the release of oxygen from haemoglobin. Which than interacts with the subunits of haemoglobin thereby decreasing its affinity for oxygen.

RBCs contain the enzyme bisphosphoglycerate mutase that catalyses the transfer of a phosphoryl group from C1 to C2 of 1,3-BPG to form 2,3-BPG.

2,3-bisphosphoglycerate phosphatase than converts 2,3-BPG to 3-PG which can re-enter the glycolytic pathway and be converted to pyruvate. Bypass ATP production step but regulating supply for 2,3-BPG that is crucial for release of O2 from hemoglobin.

Aresenate poisoning

Arsenic and phosphorus are in group V of the periodic table. Arsenate is an analogue of inorganic phosphate and can replace it in 1,3-BPG to give 1-Arseno-3-Phosphoglycerate. 1-Arseno-3-PG can be rapidly hydrolysed in water to produce 3-PG.

Step 7 of glycolysis is by-passed = no net yield of ATP

Glucose transport

Into the cells via glucose transporters, Is the first step of regulation.

Intestinal and kidney cells have Na+ dependent co-transporters called SGLT1 - glucose moves in by passive transport via facilitated diffusion.

The GLUT family makes up the other hexose transporters

GLUT family

1. GLUT 1 & 3: present in nearly all mammalian cells, continually transports glucose at a constant rate

2. GLUT 2: present in liver cells

3. GLUT 4: present in skeletal muscle cells and adipocytes. Insulin promotes rapid uptake of glucose by increasing the number of GLUT 4 receptors on the cell membrane

4. GLUT 5: transport glucose in the small intestines

5. GLUT 7: transports glucose-6-phosphate from cytosine to the ER

Regulation of glycolysis

3 enzymes:

1. Hexokinase

2. Phosphofructokinase

3. Pyruvate kinase

Hexokinase

Inhibited by glucose-6-phosphate

Phosphofructokinase

Inhibited by ATP and citrate

Activated by AMP and fructose-2,6-bisphosphate

When present in high amounts fructose-6-phosphate can be converted to fructose-2,6-bisphosphate. Thus the presence of fructose-2,6-bisphosphate indicates that lots of fructose-6-phosphate is present and thus glycolysis must occur.

Pyruvate Kinase

Inhibited by ATP

Activated by fructose-2,6-bisphosphate