Term Paper on Cori Cycle | Carbohydrates | Biomolecules | Biology

Here is a term paper on ‘Cori Cycle’ especially written for school and college students.

Under the limiting oxygen conditions experienced during vigorous exercise, the formation of NADH by glycolysis exceeds the ability of the respiratory chain to oxidize it back to NAD⁺.

The pyruvate produced by glycolysis in muscle is then converted to lactate by lactate dehydrogenase, a reaction that regenerates NAD⁺ and so allows glycolysis to continue to produce ATP. However, lactate is a metabolic dead-end in that it cannot be metabolized further until it is converted back to pyruvate. Lactate diffuses out of the muscle and is carried in the bloodstream to the liver.

Here it diffuses into liver cells and is converted back to pyruvate by lactate dehydrogenase. The pyruvate is then converted to glucose by gluconeogenesis and the glucose is released back into the bloodstream ready to be taken up by skeletal muscle (and brain). This cycle of reactions is called the Cori cycle.

Reducing power is available in a cell both as NADH and NADPH but these have quite distinct roles. NADH is oxidized by the respiratory chain to generate ATP via oxidative phosphorylation. NADPH is used for biosynthetic reactions that require reducing power. Despite their similar structures, NADH and NADPH are not metabolically interchangeable and so the cell must carry out a set of reactions that specifically create NADPH.

This set of reactions is the pentose phosphate pathway (also known as the hexose monophosphate shunt or the phosphogluconate pathway). It takes place in the cytosol and is particularly important in tissues such as adipose tissue, mammary gland and the adrenal cortex that synthesizes fatty acids and steroids from acetyl CoA. The activity of the pathway is very low in skeletal muscle, for example, which does not synthesize fatty acids or steroids.

The core set of reactions of the pathway oxidize glucose 6-phosphate to ribose 5-phosphate and generate NADPH. Thus, as well as generating NADPH, the pathway has a second important role in converting hexoses into pentose’s, in particular ribose 5- phosphate. Ribose 5-phosphate or derivatives of it are required for the synthesis of RNA, DNA, NAD+, flavine adenine dinucleotide (FAD), ATP, coenzyme A (CoA) and other important molecules. Thus the two main products of the pathway are NADPH and ribose 5-phosphate.

Main Reactions of the Pathway:

The core reactions of the pathway can be summarized as:

The pathway has three stages:

Stage 1. Oxidative Reactions That Convert Glucose 6-Phosphate into Ribulose 5-Phosphate, Generating Two NADPH Molecules:

Glucose 6-phosphate is oxidized by glucose 6-phosphate dehydrogenase to 6-phosphoglucono-8-lactone (producing NADPH) and this is then hydrolyzed by lactonase to 6-phosphogluconate. The 6-phosphogluconate is subsequently converted by 6-phospho­gluconate dehydrogenase to ribulose 5-phosphate. This is an oxidative decarboxylation (i.e. the 6-phosphogluconate is oxidized and a carbon is removed as CO₂).

These reactions are shown below:

Stage 2. Isomerization of Ribulose 5-Phosphate to Ribose 5-Phosphate:

The ribulose 5-phosphate is now converted to ribose 5-phosphate by isomerization, a reaction analyzed by phosphopentose isomerase – 

Stage 3. Linkage of the Pentose Phosphate Pathway to Glycolysis via Transketolase and Transaldolase:

If at any time only a little ribose 5-phosphate is required for nucleic acid synthesis and other synthetic reactions, it will tend to accumulate and is then converted to fructose 6-phosphate and glyceraldehyde 3-phosphate by the enzymes transketolase and transaldolase. These two products are intermediates of glycolysis. Therefore, these reactions provide a link between the pentose phosphate pathway and glycolysis.

The outline reactions are shown below:

Details of these reactions, showing the structures of the molecules involved. These reactions require xylulose 5-phosphate as well as ribose 5-phosphate. Xylulose 5-phosphate is an epimer of ribulose 5-phosphate and is made by phosphopentose epimerase – 

Overall the reactions in this stage can be summarized as –  

Control of the Pathway:

The transketolase and transaldolase reactions are reversible, so the final products of the pentose phosphate pathway can change depending on the metabolic needs of the cell. Thus when the cell needs NADPH but not ribose 5-phosphate, the latter is converted to glycolytic intermediates and enters glycolysis.

At the other extreme, when the need for ribose 5-phosphate exceeds that for NADPH, fructose 6-phosphate and glyceraldehyde 3-phosphate can be taken from glycolysis and converted into ribose 5-phosphate by reversal of the transketolase and transaldolase reactions.

The first reaction of the pathway, the oxidation of glucose 6- phosphate by glucose 6-phosphate dehydrogenase, is rate limiting and irreversible. The enzyme is regulated by NADP⁺. As the cell uses NADPH, the concentration of NADP⁺ rises, stimulating glucose 6-phosphate dehydrogenase and so increasing the rate of the pathway and NADPH regeneration.