Competency 208: Carbohydrate Metabolism

Competency 208.5.4: Enzymology and Catalytic Mechanism
Competency 208.5.5: Carbohydrate Metabolism, Adenosine

Hadassah Backman, RN

Western Governor’s University

Enzymes, are macromolecules which serve as catalysts. Catalysts are a chemical that can increase the rate of a chemical reaction or slow it down, without being changed by the reaction itself. The enzyme as a catalyst promotes the activity of the reactant which subsequently produces the product.
Enzymes have the ability to work under milder conditions, as they do not require the same level of energy, force or heat that other chemical catalysts may require to produce a biochemical reaction.
Enzymes bind temporarily to their substrates, to carry out the

catalysis. The part of the enzyme that binds directly to the substrate is called the active site. The enzyme’s active site will adjust to bind and fit the substrate to form a “lock and key” like model, which is an induced fit. Once catalysis occurs, the enzyme releases the product, which goes on to carry out its specific function, this frees up the enzyme to be recycled and to go on and facilitate a new reaction.

Fructose is a hexose sugar that is found in fruit and honey that can be used as a source of energy. Fructose requires the use of specific enzymes to break it down, to a simple, more readably available form of energy.
The steps are as follows: Catabolism of fructose begins when we ingest it by eating a fruit, the actual break down begins in the liver, with the assistance of fructokinase, an enzyme which serves as a catalyst that produces fructose 1- phosphate. Still in the liver, Aldolase B, another enzyme converts the fructose 1-phosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde. Glyceraldehyde kinase (another enzyme) can convert glyceraldehyde to glyceraldehyde 3-phosphate dehydrogenase, which at this point can be converted to pyruvate through oxidation, and which can then be converted to additional energy visa vis the Krebs Cycle in the mitochondria, resulting in ATP, i.e. energy.
Hereditary Fructose Intolerance occurs when a baby is born without the enzyme called aldolase B, which as mentioned previously, is necessary for the catabolism of fructose. Aldolase B is not present in the liver in patients with Hereditary Fructose Intolerance due to a genetic mutation. When patients with HFI ingest fructose, it will be converted to 1-phosphate with the assistance of fructokinase, however the 1-phosphate begins to accumulate in the body, causing symptoms of nausea, vomiting, diarrhea, abdominal pain, and conditions that can be fatal such as liver failure, caused by toxicity, because there is not enough free phosphate to facilitate the electron transport change, causing liver cellular activity to slow down, as the fructose-1-phosphate continues to build up. In addition to liver toxicity, the accumulation of fructose-1-phosphate also inhibits glycogen breakdown in the liver and glucose synthesis, thereby causing severe hypoglycemia.
Management of HFI requires strict adherence to a fructose, sucrose and sorbitol free diet.

The Cori Cycle is a metabolic pathway (also known as the lactic acid cycle), that encompasses both glycogenesis and gluconeogenesis.

This occurs when the muscle is undergoing rigorous exercise without sufficient oxygen supply. Anaerobic respiration takes place to support the muscles energy need. After this occurs, lactate is brought back to liver to be converted back to glucose. In the muscles, when glucose is converted to lactate it produces 2 ATP, rather than allow lactate to build up in the muscles, the second half of the Cori Cycle occurs, gluconeogenesis takes place, and reverses the both glycolysis and the fermentation, by using 6 ATP to convert lactate, to pyruvate, which can then proceed to the Krebs (citric acid cycle). If there is a mitochondrial defect present that prevents the lactate from being converted to pyruvate, limiting the Cori Cycle to the muscle cell, then the lactic acid will accumulate within the muscle cell and will result in a decreased amount of ATP production. The Cori cycle is self-limiting and will consume ATP without the ability to “re-stock” through the Krebs cycle, which produces more ATP molecules than the Cori

Cycle.
Phosphorylation of glucose to glucose-6-phosphate uses 1 molecule ATP.
Phosphorylation of fructose-6-phosphate to fructose-1, 6-bisphosphate uses 1 molecule of ATP.
Should the process remain limited to the glycolytic pathway, the following amount of ATPs will be produced at the end of glycolysis:
2 molecules of NADH are produced in the reaction when glyceraldehyde phosphate is catalyzed to s 1, 3-bisphosphoglycerate. These 2 molecules of NADH enter the electron transfer chain and produce 6 ATP.
When 1, 3-bisphosphoglycerate is phosphorylated to 3-phosphoglycerate, 2 ATP are produced.
When both PEP molecules are dephosphorylated to two pyruvates, 2 ATP are produced.

Ultimately only 10 ATP would be produced should a mitochondrial defect be present, which limits the Cori Cycle to a muscle cell.
A hypothetical defect of the enzyme succinic coenzyme A synthetase, would have catastrophic effects, as it is one of the central catalysts involved in the Citric Acid Cycle. It is the only enzyme in the citric acid cycle that produces GTP or ATP through substrate level phosphorylation. The rest of the enzymes produce products that go on to the electron carrier chain, and ultimately produce ATP, but in the Citric Acid Cycle Succinyl Coenzyme synthetase is the only enzyme responsible for producing GTP.
Without this enzyme, cells would resort to producing lactic acid in order to obtain ATP, this would ultimately result in acidosis and death. The Citric Acid cycle would cease to function because there would be no ATP present in the mitochondria to support oxidative phosphorylation, which yields the most ATP by converting the NADH and FADH produced in the citric acid cycle to

ATP.
A proton gradient is established in the mitochondria when electons from NADH and FADH2 that was produced in the citric acid cycle, flow through the electron transport chain, during oxidative phosphorylation, towards the inner mitochondrial membrane. This leaves behind a collection of H+ to accumulate within the inner membrane. The surplus of H+ is called a proton gradient, which forces hydrogen back through the membrane, causing the ions to interact with the enzyme ATP synthase which subsequently synthesizes ATP from ADP.

References:
Ahern, K., Ahern, K., & Rajagopal, I. (2012). Biochemistry Free and Easy. (pp 63–75)
Baynes, J., & Dominiczak, M. H. (2014). Medical biochemistry. Elsevier Health Sciences.
Huynen, M. A., Dandekar, T., & Bork, P. (1999). Variation and evolution of the citric-acid cycle: a genomic perspective. Trends in microbiology, 7(7), 281-291.
What is the “Cori Cycle”?. Retrieved September 26, 2016 from http://gluconeogenesis.org/what-is-the-