Kynurenine Tryptophan Cycle in Addiction

The immune system is an important part of normal body functioning. It is constantly modulating a balance between tolerance to non-harmful antigens and responsiveness to some pathogens. The process that facilitates tolerance is not known. However, recent studies show that this tolerance is due to tryptophan catabolism via the kynurenine metabolic pathway. The breakdown of tryptophan requires several enzymes which. These enzymes are found in various cells which includes those of the immune system.

Some of these enzymes involved in the breakdown of tryptophan produced through activation of the immune system. This process involves among others limitation of enzymes that are present in the dendritic cells and macrophages, 3-dioxygenase and indoleamine 2. Recent studies have shown that inhibition of these enzymes can result in the body rejecting allogeneic fetuses. This means that breakdown of tryptophan is necessary in immune tolerance aspects.

Some theories have been invented to try and explain how catabolism of tryptophan facilitates tolerance to drugs like alcohol. One such theory holds it that breakdown of tryptophan ends up suppressing proliferation of T cells by greatly reducing the supply of this amino acid that is critical in body processes. The other theory states that the down streaming of the metabolites involved in catabolism of tryptophan act as suppressors of some immune cells mainly through mechanisms of pro-apoptotic processes.

Kynurenine Tryptophan Cycle

What is tryptophan?

It is an amino acid that is required by all processes of the body for the synthesis of proteins and other body metabolic functions. Tryptophan is synthesized mainly from molecules like phosphoenolpyruvate that are present in bacteria, plants and fungi. Such organisms activate the tryptophan throughout the food chain. Animals are incapable of synthesizing this amino acid and because of this it must be taken in the diet in form of proteins which are then broken down into the respective amino acids in the digestive tract. The tryptophan that results from diet is deposited in the liver via the hepatic portal system. The protein that is not broken down in the liver enters into any of the two metabolic processes.

Because animals are incapable of synthesizing tryptophan, they must take it in the form of proteins, which are then hydrolyzed into the constituent amino acids in the digestive system. Dietary tryptophan is delivered to the liver through the hepatic portal system, and that portion which is not used for protein synthesis in the liver can then follow one of two basic metabolic fates.

In the first place, the protein that does not undergo synthesis can enter into the blood stream to later be used for synthesis of proteins and other cell functions in the body. Secondly, it can undergo degradation in the liver via a number of steps of metabolism which is basically referred to as the kynurenine pathway. Besides being a building block for proteins in the body, tryptophan also acts as the only source of substrate used for the production of important molecules in the body. Tryptophan is used in the gut and nervous system for serotonin synthesis and on the other hand pineal gland is useful in melatonin synthesis.  In case the content of niacin in the body is not enough to carry out metabolic processes, tryptophan come in to facilitate cellular cofactor synthesis and nicotinamide adenine dinucleotide (NAD +) synthesis. NAD + synthesis as research shows take place mostly in the liver.

The kynurenine pathway

The kynurenine pathway results from proteins that are not synthesized in the liver. The enzymatic reactions take place proceeding from tryptophan. The main intermediates of the metabolic system include quinolinate, 3-hydroxyanthranilate and kynurenine. A catabolic reaction is completed in the liver and this result in the total oxidation of the amino acid tryptophan and in the process carbon dioxide and adenosine triphosphate are produced.

Tryptophan metabolism and addiction

Tryptophan metabolism and addiction

 

The three stages that take place in the kynurenine pathway include an intial stage that involves tryptophan being broken down into kynurenine. The second stage starts from the produced kynurenine all the way to production of quinolinate. The final stage of the process involves enzymes that translate into total oxidation. The other processes that occurs within the three major processes picolinate production, kynuretic acid synthesis and synthesis of NAD +.

Most cells in the body have some of the enzymes that are involved in the kynurenine pathway. However, only hepatocytes have been shown to contain each and every enzyme that is used in every stage of the kynurenine pathway.  Since the liver is the only tissue in the body that contains all thes enzymes of the pathway, the liver then acts as the major site in which NAD + is synthesized from tryptophan. Diet and intake of certain substances like alcohol can affect the flow of metabolisms in the kynurenine pathway. For more information about this topic visit www.awaremednetwork.com. At AwareMed you will also find other health and awareness tips that will benefit you.

Kynurenine Tryptophan Cycle in Addiction

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