Glycolysis

Hello :) In this post we'll be discussing glycolysis. I'll outline the glycolytic pathway and list where in the cell they occur. I'll also discuss some of the major enzymes involved in glycolysis and how they can regulate this pathway.

Glycolysis

The main function of glycolysis is the catabolism (break down) of carbohydrates as glucose to produce energy in the form of ATP. Glycolysis occurs in the cytosol of all cells and may occur in the presence or absence of oxygen. In this unit we have been told to not focus on remembering the specifics of this pathway, instead we have been told to know the outline of the pathway as follows:

• Glucose, which is a 6 carbon molecule, is broken down into two 3 carbon molecules. This process involves the consumption of 2ATP molecules per molecule of glucose and is known as the investment phase.
• The two 3 carbon molecules are gradually converted to pyruvate. This involves the production of 4 ATP molecules and is known as the pay-off phase.
• In an aerobic environment, pyruvate is fed into the Tricarboxylic Acid Cycle (TCA cycle). Under anaerobic conditions pyruvate is converted to lactate which releases NAD+. This is because glycolysis is NAD+ dependent and so NAD+ needs to be recycled. 

The Regulation of Glycolysis

When we talk about enzymes, it is helpful to understand some terminology as there are different types of enzymes. A Kinase (eg.protein kinase) is any enzyme that adds a phosphate to a molecule using ATP as the phosphate donor. A phosphorylase (eg. glycogen phosphorylase) is any enzyme which adds a phosphate to a molecule using inorganic phosphate (Pi) as the phosphate donor. A Phosphatase (eg. protein phosphatase) is any enzyme that removes a phosphate from  a molecule as inorganic phosphate.

Glycolysis is regulated mainly by three different enzymes which each catalyse a particular reaction in the pathway:

1. Hexokinase: this catalyses the conversion of Glucose to Glucose-6-Phosphate which also requires the input of 1 ATP molecule which is converted to ADP. This makes glucose impermeable to the cell membrane so that it can't leak out of the cell.
2. Phosphofructokinase: this is the most important rate regulator, it catalyses the conversion of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate which requires the conversion of ATP to ADP. This enzyme is inhibited by an increase in ATP, citrate and hydrogen ions. It is stimulated by Fructose-2,6-bisphosphate and AMP. 
3. Pyruvate Kinase: this inhibits the conversion of Phosphoenolpyruvate to Pyruvate which also requires the conversion of ADP to ATP. This enzyme is inhibited allosterically by ATP and alanine and covalently by glucagon. This makes sense because glucagon is released when blood glucose levels are low and its actions try to increase blood glucose leves - glucagon acts to conserve glucose. By inhibiting pyruvate kinase, glycolysis is inhibited and glucose is spared. Pyruvate Kinase is stimulated allosterically by Fructose-1,6-bisphosphate.

Pyruvate Dehydrogenase

As I mentioned earlier, under aerobic conditions the product of glycolysis (pyruvate) is fed into the TCA cycle. During this cycle, pyruvate is converted to Acetyl Coenzyme A (Acetyl CoA) and this reaction is catalysed by Pyruvate Dehydrogenase. Pyruvate Dehydrogenase needs to be regulated because pyruvate is gluconeogenic. This means that it can be used to make glucose during starvation and thus it needs to be conserved. Pyruvate Dehydrogenase is inhibited by its reaction products - Acetyl CoA and NADH. β-oxidation (which is involved in the breakdown of fats) produces these two products, high levels of these products are found during starvation.

Pyruvate Dehydrogenase (PDH) may also be regulated by covalent modulation:

•  PDH can be phosphorylated by PDH kinase which inhibits the enzyme. 
• This is reaction is stimulated by NADH, Acetyl CoA, and ATP
• This reaction is inhibited by Calcium, pyruvate and dichloroacetate.
• PDH can be dephosphorylated by PDH Phosphatase which will activate the enzyme.
• This reaction is stimulated by insulin, calcium ions and magnesium ions. This occurs when the animal is well fed and can afford to use up some pyruvate. Calcium levels may increase due to muscle contraction during exercise, this makes sense because the animal would need extra glucose which can be obtained through the gluconeogenesis of pyruvate.

That's it for this post, if you have any questions please feel free to ask :)