Glycolysis

Glycolysis

Catabolic reactions serve to capture energy during the degradative pathways in the form of ATP. These pathways are usually oxidative and requires coenzymes such as NAD+.

Three stages in catabolism

·         Hydrolysis of complex molecules

·         Conversion of building blocks to simple intermediates like acetyl CoA

·         Oxidation of acetyl CoA

Glycolysis is a catabolic pathway for the oxidation of glucose to 2 molecules of pyruvate. Here a six carbon compound is broken down to 2 three carbon compounds. It occurs in 2 stages. Energy utilizing phase and pay off phase of energy. In most kinds of cells, the enzymes that catalyze glycolytic reactions are present in the cytosol. One common characteristic in all the enzymes involved in glycolysis is that nearly all of them require Mg2+ 

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https://bio.libretexts.org/Bookshelves/Biochemistry/Book%3A_Biochemistry_Free_and_Easy_(Ahern_and_Rajagopal)/06%3A_Metabolism_I_-_Oxidative%2F%2FReductive_Processes/6.03%3A_Glycolysis

 

Enzymes Involved in Glycolysis

  1. Hexokinase (Regulatory enzyme)
  2. Phosphoglucoisomerase
  3. Phosphofructokinase (Regulatory enzyme)
  4. Aldolase
  5. Phosphotriose isomerase
  6. Glyceraldehyde 3-phosphate dehydrogenase - Requires cofactor NAD+
  7. Phosphoglycerate kinase
  8. Phosphoglycerate mutase
  9. Enolase
  10. Pyruvate kinase (Regulatory enzyme)

 

Among the 10 reactions in glycolysis only three reactions are irreversible and are the regulatory reactions in glycolysis.

 

Regulation of glycolysis

Hexokinase

In most tissues phosphorylation of glucose is catalyzed by hexokinase. It is inhibited by its own product glucose 6 phosphate. This enzyme has broad specificity and has low Km for glucose. This enzyme permits phosphorylation of glucose even at low concentrations. This enzyme has an isoform called glucokinase and is present in liver cells and pancreas. It has high Km than hexokinase and this enzyme function as glucose-sensor in β cells for insulin secretion. This enzyme function only in liver cells and effectively remove flood of glucose delivered by the portal blood. Controls hyperglycemia during absorption of food.

Phosphofructokinase ( PFK-1)

Most important control point in glycolysis. Rate limiting step.

PFK-I is allosterically inhibited by elevated levels of ATP, citrate (energy rich conditions) and is activated by high concentration of AMP.

Fructose 2,6 bisphosphate is the most potent activator of PFK-I and are able to activate even in high concentration of ATP. Fructose 2,6 bisphosphate is formed by the action of PFK-2 which is a bifunctional enzyme having both kinase and phosphatase activity and catalase both forward and reverse reactions. Decrease levels of glucagon and elevated levels of insulin cause an increase in fructose 2,6,bisphosphate.(Well fed state)and ( reverse in starvation.)

Pyruvate kinase

Pyruvate kinase is allosterically activated by fructose 1,6 bisphosphate

Covalent modification of pyruvate kinase

Phosphorylation of cAMP dependent protein kinase leads to inactivation of pyruvate kinase in liver. During low glucose levels, elevated levels of glucagon increases cAMP and causes phosphorylation and inactivation of pyruvate kinase. 

Arsenic poisoning            

It is due to the inhibition of enzymes such as pyruvate dehydrogenase, which requires lipoic acid as cofactor. Arsenate also prevent net ATP and NADH production in glycolysis. Poison competes with inorganic phosphate as a substrate for Gly-3 PO4 dehydrogenase and form a complex and hydrolyses to 3 phosphoglycerate. Here the energy producing steps are bypassed.

The overall process of glycolysis results in the following events:

  1. Glucose is oxidized into pyruvate.
  2. NAD+ is reduced to NADH.
  3. ADP is phosphorylated into ATP.
            1. Energetics of Glycolysis 
  4. In anaerobic glycolysis energy yield is 2ATP. Total 2 are produced and 2 are used in the first phase of the reaction. In aerobic glycolysis NADH formed is utilized in oxidative phosphorylation for the production of ATP.

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