Tag Archives: ATP

A Pain Relief that is 8 Times More Effective Than Morphine

PAP

A groundbreaking treatment for pain, eight times stronger than morphine, has been discovered by scientists. The revolutionary technique involves an injection of the protein prostatic acid phosphatase (PAP), which can combat serious discomfort for more than three days — an astonishing 14 times as long as the five hours of pain relief brought about with a dose of morphine.

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The substance appears to have few side effects, and works by neutralizing the chemical in your body that causes your brain to feel pain.

A research team pinpointed the identity of a particular “pain protein” in nerve cells, and then found a way of converting it from a substance that causes pain into one that suppresses it.

When nerve cells are in distress, they release a chemical known as adenosine triphosphate (ATP) which creates the sensation of pain. PAP converts the ATP into adenosine — which actually suppresses pain.

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SAMe (S-Adenosyl methionine )

Other Names: SAM-e, S-adenosylmethionine

Definition:-
S-Adenosyl methionine (SAM) is a coenzyme involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase EC 2.5.1.6. Transmethylation, transsulfuration, and aminopropylation are the metabolic pathways that use SAM. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver.

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The methyl group (CH3) attached to the methionine sulfur atom in SAM is chemically reactive. This allows donation of this group to an acceptor substrate in transmethylation reactions. More than 40 metabolic reactions involve the transfer of a methyl group from SAM to various substrates such as nucleic acids, proteins, and lipids.

In bacteria, SAM is bound by the SAM riboswitch, which regulates genes involved in methionine or cysteine biosynthesis.

The supplement SAMe is a synthetic form of a compound formed naturally in the body from the essential amino acid methionine and adenosine triphosphate (ATP), the energy-producing compound found in all cells in the body. It was first discovered in 1953.

SAMe is believed to work by being a methyl group donor in many reactions in the body. After donating the methyl group, it is converted to a compound called S-adenosyl-homocysteine.

Properties:-
Molecular formula: C15H23N6O5S+
Molar mass: 399.447

Biochemistry of S-adenosyl methionine:-

SAM cycle
The reactions that produce, consume, and regenerate SAM are called the SAM cycle. In the first step of this cycle, the SAM-dependent methylases (EC 2.1.1) that use SAM as a substrate produce S-adenosyl homocysteine as a product. This is hydrolysed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase EC 3.3.1.1 and the homocysteine recycled back to methionine through transfer of a methyl group from 5-methyltetrahydrofolate, by one of the two classes of methionine synthases EC 2.1.1.13 or EC 2.1.1.14. This methionine can then be converted back to SAM, completing the cycle.

Polyamine biosynthesis
Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by Adenosylmethionine decarboxylase EC 4.1.1.50 to form S-adenosyl-5′-3-methylpropylamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.

SAM is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as dopamine and serotonin. Methyltransferases are also responsible for the addition of methyl groups to the 2′ hydroxyls of the first and second nucleotides next to the 5′ cap in messenger RNA.

Therapeutic uses
In the United States, SAM is sold as a nutritional supplement under the marketing name SAM-e (also spelled SAME or SAMe; pronounced “sam ee”). SAM is also marketed under the Gumbaral, Samyr, Adomet and Admethionine brand names. Some research has indicated that taking SAM on a regular basis may help fight depression, liver disease, and the pain of osteoarthritis. An authoritative report on SAMe is from the Agency for Healthcare Research and Quality (Dept Health and Human Services) at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.2159. Multiple clinical trials indicate benefits for depression, some liver conditions and osteoarthritis. All other indications are not yet proven.

Therapeutic use of SAM has increased as dietary supplements have gained in popularity, especially after the Dietary Supplement Health and Education Act was passed in 1994. This law allowed the distribution of SAM as dietary supplement, and therefore allowed it to bypass the regulatory requirements for drugs of the Food and Drug Administration (FDA).

At first, a line of evidence suggested that abnormally low levels of endogenous SAM may play an important role in the development of Alzheimer’s disease (AD) and that SAM may therefore have therapeutic potential in the treatment of AD (further research indicates this effect is likely due to Vitamin B12 deficiencies, which cause neurologic defects through one carbon transfers with folate). Severely low levels of SAM have been found in the cerebrospinal fluid and in all brain regions of AD patients examined. Preliminary research suggests SAM may have therapeutic potential in treating AD patients and a recent study using a mouse model of AD found that supplementary SAM prevented oxidative damage and cognitive impairment. In that study (available online), Tchantchou et al also explain the biomechanics that in addition to the above findings make low SAM a likely causal component of AD pathology.

Oral forms:
Oral SAMe achieves peak plasma concentrations 3 to 5 hours after ingestion of an enteric-coated tablet (400 – 1000 mg). The half-life is about 100 minutes. It may require up to one month for it to reach full effectiveness in treating osteoarthritis. Because of structural instability, stable salt forms of SAM are required for its use as an oral drug. The University of Maryland lists the commonly used salts: tosylate, butanedisulfonate, disulfate tosylate, disulfate ditosylate, and disulfate monotosylate.

With the advent of FDA-mandated Good Manufacturing Practices (GMPs) in 2008, manufacturers are required to confirm that their products contain what is listed on the label through the end of shelf life. Whether they achieve this goal or not has been questioned. Subscribers to Consumer Labs have access to a comparative report on SAMe content of various supplements.

Claims that the SAMe butanedisulfonate salt is more stable or better absorbed are not supported by the references that are usually cited as evidence. Different salts have successfully been used in clinical trials, but there is no published head-to-head comparison

Usage
SAMe is best absorbed on an empty stomach. Enteric-coated tablets packaged in foil or foil blister packs increase stability and improve absorption. SAMe should be stored in a cool, dry place to prevent deterioration.
People Use SAMe In:-
Osteoarthritis
There have been a number of studies on the effectiveness of SAMe in the treatment of osteoarthritis. SAMe appears to diminish osteoarthritis pain as effectively as non-steroidal anti-inflammatory medication. It appears to be well-tolerated.

Depression
There have been a number of studies on the use of SAMe for depression. It has been hypothesized that SAMe increases the availaibility of neurotransmitter serotonin and dopamine.

Liver disease
Some evidence suggests that SAMe may help people with liver disease. Preliminary research suggests it may help to normalize liver enzyme levels and help with cholestasis.

Possible side effects:-
SAM-e & Homocysteine: Once SAM-e donates its methyl group to choline, creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Under normal circumstances, homocysteine, in the presence of Vitamin B6, B12, and folic acid (SAM-e’s main co-factors), will eventually be converted back into methionine, SAM-e, or cysteine, glutathione, and other useful substances. However, if adequate amounts of these vitamins are not present, SAM-e will not break down properly. As a consequence, the full benefits of SAM-e will not be obtained, and homocysteine may increase to unsafe levels.

High levels of homocysteine have been associated with atherosclerosis (hardening and narrowing of the arteries), as well as an increased risk of heart attacks, strokes, liver damage, and possibly Alzheimer’s disease. Therefore, Vitamin B supplements are often taken along with SAM-e. These vitamins help metabolize the homocysteine into other useful compounds.

Another reported side effect of SAMe is insomnia, therefore the supplement is often taken in the morning. Other reports of mild side effects include lack of appetite, constipation, nausea, dry mouth, sweating, and anxiety/nervousness, but in placebo-controlled studies these side effects occur at about the same incidence in the placebo groups.

Therapeutic doses range from 400 mg/day to 1600 mg/day, although higher doses are used in some cases. Consult with your physician before and during use.

Adverse effects:-
Gastrointestinal disorder, diarrhea, dyspepsia, anxiety, headache, psychiatric, insomnia, allergy, and rashes. Long-term effects are unknown.

Serotonin syndrome:
There is concern and one report of the potentially fatal serotonin syndrome in association of SAMe with other medications.

Induction of mania:
In an extensive MEDLINE search on SAMe, Kagan found induction of mania in one patient out of fifteen treated with parenteral SAMe. In the same review, Lipinski found the apparent induction of mania in two patients with bipolar disorder (total of nine depressed patients studied).Both depression and mania can be life-threatening conditions that may cause cognitive dysfunction even after remission. There is concern that antidepressants in general can induce hypomania, mania, or both.

The safety of SAMe during pregnancy and during breastfeeding is unknown.

People with bipolar disorder, anxiety disorders and other psychiatric conditions should only use SAMe under the supervision of their healthcare provider. SAMe has been associated with hypomania and mania.

The most common side effects are digestive complaints, particularly nausea. Other side effects include skin rash, lowered blood sugar, dry mouth, blood in the stool, thirst, increased urination, headache, hyperactivity, anxiety and insomnia.

People with Parkinson’s disease should avoid SAM-e.

For more knowledge you may click to see
:->

S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease (Evidence Report/Technology Assessment:)

What Is SAMe

Disclaimer:The information presented herein is intended for educational purposes only. Individual results may vary, and before using any supplements, it is always advisable to consult with your own health care provider.

Resources:
http://en.wikipedia.org/wiki/S-Adenosyl_methionine
http://altmedicine.about.com/od/treatmentsfromatod/a/SAMe.htm

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Creatine

w:CreatineImage via Wikipedia

 

Other Names: creatine monohydrate, creatine phosphate, creatine citrate

Definition:Creatine is nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to muscle and nerve cells. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle, which he later named creatine after the Greek word for flesh, Kreas.

It is a compound that’s involved in the production of energy in the body, in the form of adenosine triphosphate (ATP). Made in the liver, approximately 95% of the body’s creatine ends up being stored in skeletal muscles and the remaining 5% is found in the brain, heart and testes. Once it’s used, creatine is converted to a waste product called creatinine and excreted in urine.

Functions:

Creatine, by way of conversion to and from phosphocreatine, functions in all vertebrates and some invertebrates, in conjunction with the enzyme creatine kinase. A similar system based on arginine/phosphoarginine operates in many invertebrates via the action of Arginine Kinase. The presence of this energy buffer system keeps the ATP/ADP ratio high at subcellular places where ATP is needed, which ensures that the free energy of ATP remains high and minimizes the loss of adenosine nucleotides, which would cause cellular dysfunction. Such high-energy phosphate buffers in the form of phosphocreatine or phosphoarginine are known as phosphagens. In addition, due to the presence of subcompartmentalized Creatine Kinase Isoforms at specific sites of the cell, the phosphocreatine/creatine kinase system also acts as an intracellular energy transport system from those places where ATP is generated (mitochondria and glycolysis) to those places where energy is needed and used, e.g., at the myofibrils for muscle contraction, at the sarcoplasmic reticulum (SR) for calcium pumping, and at the sites of many more biological processes that depend on ATP.

Biosynthesis:
In humans, about half of the daily creatine is biosynthesized from three different amino acids – arginine, glycine, and methionine. The rest is taken in by alimentary sources. Ninety-five percent of creatine is later stored in the skeletal muscles.

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The enzyme GATM (L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.

The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas.

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.

Controversy:While creatine’s effectiveness in the treatment of many muscular, neuromuscular, and neuro-degenerative diseases is documented, its utility as a performance-enhancing food supplement in sports has been questioned (see creatine supplements for more information). Some have even proposed that its use as a performance enhancer should be banned. Despite this, creatine remains very popular.

Sources:
In humans, approximately half of stored creatine originates from food (mainly from fresh meat). Since vegetables do not contain creatine, vegetarians show lower levels of muscle creatine which, upon creatine supplementation, rise to a level higher than in meat-eaters.

Creatine is found in small amounts in red meat and fish. However, much of it is destroyed by cooking. It’s also made naturally in the body from L-arginine, L-glycine and L-methionine, amino acids that are principally found in animal protein. Insulin is needed for creatine to enter muscles, so consuming carbohydrates with creatine may increase the amount of creatine available to muscles.

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Creatine supplements are available in capsules or as a powder at health food stores, some drug stores and online. One of the most popular forms of creatine is creatine monohydrate.

Side effects:-

In the Cochrane Collaboration analysis of 12 trials, there were no notable adverse events reported, however, research on the side effects and safety of creatine supplements is still limited.

Possible side effects of creatine include:

*Stomach cramps

*Nausea
*Diarrhea

*Loss of appetite

*Muscle cramps

*Weight gain

Creatine may cause water to be drawn away from other areas of the body and into muscle tissue, which could increase the risk of dehydration.

High doses of creatine could potentially injure the kidneys, liver and heart. Theoretically, creatine may cause kidney damage because its by-product, creatinine, is filtered through the kidneys into urine. Although studies haven’t found adverse events in recommended doses, there have been a couple of case reports of people who have experienced kidney collapse and three deaths in people taking creatine, but there is no definitive evidence that creatine was the cause. People with kidney disease or liver disease should avoid creatine.

Creatine supplements may cause asthmatic symptoms, such as wheezing and coughing, in some people.

People with McArdle’s disease shouldn’t use high doses of creatine because it has been found to increase muscle pain.

There is some concern that oral creatine supplements are metabolized in the body to a toxic waste product formaldehyde, which could potentially damage cells, DNA molecules and blood vessels.

Pregnant or nursing women or children should not use creatine supplements.

One of the main safety concerns is that individuals using creatine to enhance athletic performance or muscle mass, particularly adolescents, may exceed recommended dosages and take it without supervision.

Short-term use of creatine in healthy individuals is generally considered safe (see Creatine supplements#Safety). , studies have not yet been able to demonstrate either long-term or short term creatine supplementation result in adverse health effects. Creatine supplementation utilizing proper cycling and dosages has not been linked with any adverse side effects beyond occasional dehydration due to increased muscular water uptake from the rest of the body.[13] In fact, an increase in body mass because of increased muscle hydration is the most widely accepted side effect of creatine supplementation[14][15].

According to the opinion statement of the European Food Safety Authorities (EFSA) published in 2004 it was concluded that “The safety and bioavailability of the requested source of creatine, creatine monohydrate in foods for particular nutritional uses, is not a matter of concern provided that there is adequate control of the purity of this source of creatine (minimum 99.95%) with respect to dicyandiamide and dihydro-1,3,5-triazine derivatives, as well as heavy metal contamination. The EFSA Panel endorses the previous opinion of the SCF that high loading doses (20 gram / day) of creatine should be avoided. Provided high purity creatine monohydrate is used in foods for particular nutritional uses, the Panel considers that the consumption of doses of up to 3g/day of supplemental creatine, similar to the daily turnover rate of creatine, is unlikely to pose any risk”.

This opinion is corroborated by the fact that creatine is a natural component in mothers’ milk and that creatine is absolutely necessary for brain development in the human embryo and the baby, as well as for optimal physiological functioning of the adult human body, especially the brain, nervous system, the muscles and other organs and cells of high energy expenditure, where the creatine kinase (CK) system is highly expressed and creatine levels are high.

Side effects that produce lower leg pain may be associated with the use of creatine. Creatine may be the cause of an increase in the anterior pressures of the lower leg. This is usually found in post-creatine use when at rest and after exercise. Normal at-rest pressures have been found to be highly elevated by subjects who used creatine within the prior 35 days when compared to no supplementation. This can produce an extreme amount of pain in the lower leg due to the rigidity of the anterior compartment of the lower leg and lack of fluid drainage out of the compartment. It may also be exasperated by the increase of water content in the muscle fibers, putting more pressure on the anterior compartment. If this condition persist, check with your doctor and inform them of your creatine use and dosage. Although this condition may and usually does subside, if left untreated complications may occur that require emergency medical attention. If the levels remain high for a long period of time, irreversible damage to tissue may occur, particularly to the peroneal nerve. These conditions can further be found under Chronic Compartment Syndrome.

Creatine and the treatment of muscular diseases:
Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (arthritis, congestive heart failure, Parkinson’s disease, disuse atrophy, gyrate atrophy, McArdle’s disease, Huntington’s disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).

Two studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study demonstrated that creatine is twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to cell death.

Second, creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.

Third, creatine has been shown to be beneficial as an adjuvant treatment for several neuro-muscular and neuro-degenerative diseases and its potential is just beginning to be explored in several multi-center clinical studies in the USA and elsewhere.

Resources:
http://en.wikipedia.org/wiki/Creatine
http://altmedicine.about.com/od/creatine/a/creatine.htm

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