Kynurenine Tryptophan Cycle in Addiction

February 16, 2015

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

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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GABA Metabolism in the CNS in Addiction

February 14, 2015

GABA Metabolism in the CNS in Addiction

What is GABA?

Known as Gamma-Amino Butyric acid, it is an amino acid that performs functions of neurotransmitters in the brain.it is the most abundant neurotransmitters occurring in the central nervous system (CNS).it acts as an inhibitor of transmissions in the brain thus in the process calming down activities in the nervous system. It is found as a supplement in which it acts as a natural tranquilizer. It has been shown to increase levels of human growth hormones thus is very popular among body builders.

The Neurotransmitters Question

The brain is made up of millions of cells. Communication takes place from one brain region to another through neurotransmitters. Neurons are individual cells of the nerves that make up the nervous system. They serve as the wiring for the body to transmit information form one region to another. The electrical signals generated are transported through the neurons as a single impulse. Ones the impulses reaches the end of the neurons, it is transmitted to the other cell through neurotransmitters.

The central nervous system consists of the spinal cord and the brain. The two consist of neurotransmitters which pass from one end of the neuron to another. The peripheral nervous system which is made up of nerves that run to the rest of the body. The nerves transmit chemical signals from one neuron t adjacent gland cells and muscles.

GABA and glutamate are the most abundantly occurring neurotransmitters in the nervous system. The two are in abundance in the cerebral cortex which is the region where interpretation of sensation takes place and thinking occurs. The ending of the neurons are made up of sac like structures which are filled with neurotransmitters.

GABA

When the chemical and electrical signals reach the end of the neurons, they trigger the sacs to release neurotransmitters to act as a bridge between one nerve cell and another. The spaces called synapses act as a bridge through which signals pass to the other cells. On reaching the other neuron, the neurotransmitters attach to the cell receptors. This triggers the electric impulse to move from the end of the nerve cell neuron to the other cell completing the message transmission and triggering and effect.

Role of GABA In the Brain

It is formed in the cells of the brain from glutamate. GABA acts as an inhibitory neurotransmitter which simply means that it blocks nerve impulses in the brain. On the other hand, glutamate from which GABA is formed is an excitatory neurotransmitter. When it binds to cells adjacent to it, it activates them to send impulses throughout the brain from one cell to another. GABA instead of telling the brain to activate and send impulses, it tells it he opposite. It stimulates the brain not to send nerve impulses from one cell to another.

In the absence of GABA nerve cells tend to activate more often sending signals regularly. Disorders associated with anxiety such as headaches, addiction, panic attacks, Parkinson syndrome, cognitive impairment and seizures are all linked to low activity of GABA.

It naturally hinders nerve impulses transmission from one cell to another. It brings about a calming effect in the process. The best way to understand the significance of GABA is by understanding the effects of caffeine on the brain. Caffeine acts as an inhibitor of the release of GABA. When the levels of GABA are low in the brain, more nerve transmissions take place. This leads to the sensational feeling that one gets when they takes coffee. This feeling is as a result of activity of glutamate with less GABA.

The reason why, caffeine does this is simply because other molecules tend to bind with the neurons near the site where GABA binds with these neurons. This is exactly the way that basic tranquilizers like barbiturates and Benzodiazepines work. They increase the effects of GABA in the body which in turns inhibits the transmission of nerves.

GABA Metabolism

It is synthesized in a metabolic path known as the GABA shunt. The first step in GABA formation uses a-ketoglutarate that is formed from metabolism of glucose in the Kreb’s cycle. Afterwards a-ketoglutarate is processed by a-oxoglutarate to form glutamate. In the final process, the glutamate undergoes decarboxylation to form GABA through the glutamic acid decarboxylase enzyme. Like other neurotransmitters, GABA is stored in the synaptic vesicles of the brain and is only released when depolarization of the presynaptic membrane takes place.

GABA

GABA and Addiction

Alcohol consumption leads to loss of coordination of the motors as well as sedation as other high levels of inhibitory transmitters do. Studies therefore show that GABA effects contribute to some effects of alcohol in the brain. Past studies show that, GABA as an inhibitory neurotransmitter is affected by alcohol consumption. Continuous alcohol consumption leading to addiction lead to decline in GABA receptors found in the brain and his reduces the ability of the neurotransmitter t bind with cell receptors.

In this case, the body is forced to find ways to compensate for the declined levels of GABA neurotransmitters. These effects are responsible for brain function changes that lead to things like dependence and alcohol tolerance. When one withdraws from alcohol, the stimulating effects on the neurotransmitter disappear. The body has very few GABA receptors needed to balance the effects of excitatory neurotransmitters. Because of this the brain has too many excitatory nerve signals being transmitted. This translates to psychological and physical effects of alcohol addiction and withdrawal.

Dr. Dalal Akoury has years of experience with patients of addiction and other health conditions. This enables her to provide wise counsel to patients who may be going through certain health conditions. Many of these patients have gotten better and they now bear witness to her god works. To become part of this community and to receive regular health and awareness tips that will befit you, visit www.awaremednetwork.com today.

GABA Metabolism in the CNS in Addiction

Histamine, Metabolism, Neuro-excitatory and Neurotransmitters

February 10, 2015

Role of Histamine, Metabolism, Neuro-excitatory and Neurotransmitters for Addiction

Histamine refers to transmitter that is endogenous in nature and one that is involved in gastric secretions, allergic manifestations and vigilance regulation. It is found in tissues of all animals especially mamma also with high concentrations in the skin, liver and lungs. In the tissues, the transmitter histamine occurs in mast cells which are simply a group of cells whose cytoplasm has high concentrations of basophilic granulations.

In the mast cells histamine exists bonded to acidic compounds like heparin. In most cells with histamine, its production is slow and when it sis depleted t may take several weeks to go back to normal levels. The brain also contains histamine in certain level. Histamine occurs in the brain region in the hypothalamus based o circadian rhythm which occurs in the brain. Its concentration in the plasma does not exceed 1 microgram per liter but this concentration is high in patients suffering from asthma.

neurotransmitters

In the blood the level of histamine ranges from 10 to 100 micrograms in a liter and is primarily concentrated in the basophils. This concentration as studies show rises especially in patients suffering from medical conditions like gastrodudenal ulcers and chronic myelogenous leukemia. Histamine depreciates some times in the body. This means that more has to be produced to replace the one that is lost. This replacement is often slow and can take several weeks. However, histamine renewal in the nervous system and the gastric cells is at faster rate because it is released continuously.

Histamine and Metabolism

Naturally the distribution of histamine in the body is not usually uniform. It however, occurs in in higher concentrations in the mucosa of the gastric system. Its metabolism is dependent on enzymes such as diamine oxidase, histamine N-methyltransferase and histidine decarboxylase. These enzymes seem to be dominant in the stomach region. Studies have been carried out to determine exactly the concentration of histamine in the gastric system. For years this has been a subject of controversial debate and it was only recently that a solution was found. Studies show that the inactivation process of histamine by histamine methyltrasferase takes place in the gastric mucosa that has a significant activity of enzymes.

However it is worthwhile to note that the intestines, liver and spleen have much higher activities which points towards little specification of catabolism of histamine in the gastric mucosa. There have also been debates concerning the activity of diamine oxidase which for years was thought not to exist in the corpus mucosa. Recent studies however, show that moderate enzyme activities of this enzyme is present in some species among them man. In this case then, the metabolism of histamine n the gastric mucosa does not mean its existence in mammalian tissues. Activities of these enzymes could also act as an indication that it has significant physiological functions in the body.

The formation and inactivation of histamine has been shown to be regulated through enzyme activities by during the process of secreting acid. Histamine N-methyltrasferase and histidine decarboxylase are enhanced by gastrin activities and not necessarily influenced by vagal stimulation.

Neuro excitatory and Neurotransmitters for Addiction

Studies show that rugs especially alcohol affect to a great extent the brain as well as some physical processes of the body. There are several reasons that make a person an alcohol addict. These reasons may range from depression, stress, impulse of just mere pleasure. Once a person becomes alcohol dependent, a pattern has already been established and this affects the neural system of the person.

Histamine

The Neurotransmitter Process

In order to fully understand the neurological effects of alcohol addiction in the brain, there is need to understand how the brain transmitters work. The brain communicates through neurons that send messages form ne cells of the brain to an0ther. Transmission of nerve signals takes place from one brain region to another. Once a neuron has been activated, an electrical signal is produced which travels all through the membrane that surrounds the body and axon of the neuron. The signal reaches the end of the neuron and this triggers neurotransmitters to be released from the brain cells. The neurotransmitters then travel from one neuron to another. On reaching the other neuron, the molecules in the transmitter bind with receptors in the neuron and this triggers new electric signal to be produced. Production of new signals depends on the type of neurotransmitter that is involved in the process.

Most neurotransmitters exhibit inhibitory and excitatory effects. This is dependent on the region of the brain and the receptors present in that region. Neurotransmitters with excitatory effects include among others glutamate, dopamine and serotonin while those with inhibitory effects include gamma-aminobutyric acid most commonly referred to as GABA. When one takes alcohol it tends to reinforce the transmitter system. This affects many neural transmitter processes which trigger some long term effects like withdrawal, tolerance, dependence, sensitization and finally addiction.

This information can be found for free at www.awaremednetwork.com. Here you will also find other health and awareness tips.

Role of Histamine, Metabolism, Neuro-excitatory and Neurotransmitters for Addiction

Methylation and Addiction

February 6, 2015

The Mechanisms in Methylation and Addiction

Addiction refers to a very strong need to take something like drugs or do particular activities. Addictions are so strong that people think they have no control over them. Addiction becomes one of the important things in your life. Due to this it ends up affecting the quality of your life as well as your relationship with others.

Addiction occurs when one feels they should take something like drugs or alcohol or carry out a particular activity such as gambling. Today addiction affects people across all ages. There is no known reason why people get addicted to something. However, regular intake of drugs or gambling may result in the person’s life getting tuned to that particular choice. People get strongly attached to these things and they feel the need to repeat the same thing over and over again. This way they become addicted to that thing and it becomes an important part of their life.

What is methylation?

Methylation basically refers to the process of adding a methyl group to a substance or simply replacement of an atomic group with that of a group of methyl. It is takes place where a methyl group undergoes alkylation instead of the normal hydrogen atom replacing a carbon chain. Such terms apply in biochemistry, chemistry, biological sciences as well as soil science.

Methylation and Addiction

In biological sciences for instance methylation involves the enzyme catalyzation. This form of methylation is responsible for heavy metal modification, gene expression regulation, processing of RNA as well as regulation the functioning of proteins in the body. Heavy metal methylation often takes place outside the biological system. Reduction of histological staining is made possible by the chemical methylation of tissues in the body.

Methylation in the body

It is one of the important processes that take place in the body. It takes place when the body receives a substance and converts it to another. This is basically so that the substance can be removed from the body. Methylation takes place in the liver during the second detoxification phase a billon times per second.

In order to understand detoxification, there is need to look at what makes up a methyl group. A methyl group is basically made up of three atoms of hydrogen. Methylation takes place when S-adenosine methionine (SAMe) gives out a methyl group that is then attached to the molecule that undergoes detoxification. The SAMe s then converted to homocysteine. The methylation process must occur often in order to detoxify the body regularly. Buildup of toxics in the body leads to poisoning of cells which can lead to serious medical conditions a like inflammation and cancer. The methylation process is kept going by vitamin B12, B6 as well as folic acid. These substances are necessary in the body in order to facilitate homocysteine reduction to facilitate the process of methylation.

Homocysteine is an amino acid that is naturally toxic to the body. If left to accumulate it can prove toxic to the cells leading to several health conditions. If methylation does not take place as it should a person can suffer from conditions like stroke, cancers of the reproductive system, colon cancer, Alzheimer’s disease, heart disease, defects of the neural tubes, impairment in DNA repair, kidney infarct, impaired detoxification and dysplasia among others.

Faulty methylation leads to the levels of homocysteine increasing. This leads to poisoning of the cells and tissues. However, studies show that B vitamins facilitate lowering of the levels of homocysteine in the body and therefore reducing the risk of a person getting disease like stroke and heart attack. Common belief among people is that the main cause of heart attack is in accumulation of cholesterol in the body therefore they cut out their intake of cholesterol in their foods. However, studies show that only a fraction of people who suffer from heart attacks is as a result of cholesterol build up in the body. This being the case, other people who suffer from heart disease may be because of buildup of homocysteine in the body.

Methylation and Addiction

Recent research studies show that over exposure to certain drugs facilitates chances in methylation levels in the bloods. The same also promotes DNA methylation levels to be altered. DNA methylation takes place in the brain neurons. The altered level of methylation promotes altered levels in gene expression this can happens when one is addicted to certain substances like drugs and alcohol.

Basically methylation is used in DNA. Naturally, each cell in the body contains DNA of other cells. Methyl groups that occur naturally in the body are responsible from suppression of DNA that should not be read. When there is poor methylation due to an addiction to drugs or alcohol, the methyl groups are removed from the genes in order to be used in other body processes. This removal of a methyl group is what leads to cancer expression in the body.

For more information about methylation and addiction, visit www.awaremednetwork.com today. Here you will also find other helpful health and awareness tips. Dr. Dalal Akoury will provide assistance with any information you may need.

The Mechanisms in Methylation and Addiction

NAC, the Cystine-Glutamate Antiporter and Addiction

February 5, 2015

NAC, the Cystine-Glutamate Antiporter and Addiction

Addiction is one complex problem faced by many. There is no limit to how many things people can get addicted to. If you cannot go a day without watching a movie, and then it gets to a point when you must slot in a couple of hours in your daily schedule to watch movies then that is your addiction.

If you keep getting those cravings for soda or sugary meals, you try to stay without them but the urge is so much that you only calm down after satisfying that thirst then that is an addiction.

Addiction can be good or bad. You can be addicted to work, you love your work that you can’t spend time away from your job. That is addiction. Such positive addictions too may be unhealthy. If you are addicted to work for instance, you will hardly spare time for other essential activities, such as being with your family.

Other forms of addiction often associated with the term, such as drug and substance abuse are detrimental to your health. A person who is addicted to alcohol for instance cannot live without it. Their lives often revolve around the liquor. The same applies to coke, cigarettes, marijuana and all other recreational drugs. The substance of addiction gets to dictate how you live your life.

the Cystine-Glutamate Antiporter

Facts about addiction

The habit is a problem. You have to first admit it in order to be able to get over it. An addict who finds it difficult to get over the problem may often be tempted to blame it on someone, or something else. But that is not a solution, acceptance is key.

Giving in to one’s yearnings is a matter of choice. At the beginning of any addiction you often see yourself in control of the situation. You are not forced to do anything, you just do it because you enjoy the act. With time though, this control diminishes and you become increasingly more vulnerable to the substance of your addiction.

You are in a position to drop your addictions by saying ‘no’ to the substance. This is the premise under which psychosocial support for addiction recovery is usually built. Through guidance one is offered a way out of their drug or substance habit. At such point, it is upon you to decide whether or not you are going to adopt a clean lifestyle.

NAC and Addiction

N-Acetyl L-Cysteine is a chemically changed version of the non-essential amino acids in the body. NAC works by purifying your body by removing harmful toxins. It is highly essential in recovery from drug addiction. alcohol and other drugs commonly abused cause a lot of damage to the liver, lungs, kidneys and other organs and this is likely to result in chronic ailments that are life threatening. This amino acid is essential as it protects cells from getting damaged in addition to its role in preserving functions of the liver.

It is a known precursor to Glutathione which is the most effective in destroying free radicals. The amino acid works to protect the brain and the liver from damages caused by toxins like alcohol, acidic mater, particles found in the air and cigarettes smoke. It also has other significant functions that are key to the wellbeing of an individual.

Among them, it helps the body to promote its burning of fat and aids the muscle building process. Studies also indicate that it can rid the body of copper by a chelating effect, and is used in the treatment of particular diseases including bronchitis, emphysema and certain respiratory problems among adults.

NAC plays a key role in the production of white blood cells necessary for body immunity. The white cells fight diseases that attack the body and help boost the natural immune response of the body. As such, the amino acid is essential for the defense of the body against disease attack. It further helps in insulin metabolism and functions, which is key to the body’s blood sugar regulation.

the Cystine-Glutamate Antiporter

Sources of NAC

N-Acetyl L-Cysteine can always be naturally manufactured by the body on its own. The high-protein foods such as eggs and meat are however potent dietary sources of this amino acid. Other good sources include foods such as broccoli, garlic, wheat, onions and red peppers.

Other sources that can be recommended for this important amino acid for those who are recovering from the damage caused by drug addiction include nutritional supplements found in a number of nutrition outlets in different continents. It is however important to seek recommendations form a physician since this product is largely unregulated and health consumers are likely to purchase a product that contains incorrect amount of ingredients recommended for the particular patient.

NAC, the Cystine-Glutamate Antiporter and Addiction

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