Homocysteine metabolism

( Marja-Leena Silaste 2003 ) .

Homocysteine metamorphosis can be found at the intersection of two tracts which are: remethylation to methionine, it requires folate and vitamin B12 ; and transsulfuration to cystathionine, it needs pyrodoxal-5′-phosphate. S-adenosylmethionine as a accountant which coordinates the two tract in bend becomes an allosteric inhibitor of the methylenetetrahydrofolate reductase reaction and act as an activator of cystathionine beta-synthase. ( Annu Rev Nutr, 1999 ) Homocysteine is synthesized from methionine through a multi-step procedure. First of all, methionine will have an adenosine group from adenosine triphosphate which is catalyzed by S-adenosyl-methionine synthetase, giving a S-adenosyl methionine ( SAM ) . The methyl group is transferred by SAM to an acceptor molecule. Following, L-homocysteine is produced by hydrolysing the adenosine from the old ATP. Apart from at that place, L-homocysteine can either be converted back into L-methionine by tetrahydrofolate ( THF ) or transition to L-cysteine from the information provided by & lt ; hypertext transfer protocol: //en.wikipedia.org/wiki/Homocysteine & gt ; . Actually some of the extra homocysteine might be used to bring forth cysteine, which so yield glutathione. Glutathione is a powerful antioxidant. The transition of homocysteine into glutathione may be increased when the organic structure is under oxidative emphasis harmonizing to & lt ; hypertext transfer protocol: //www.lef.org/protocols/heart_circulatory/homocysteine_reduction_01.htm & gt ; .

Talking of lift of homocysteine degree in our blood, really it may due to enduring from oxidative emphasis or the methylation sum lessenings, which causes indirectly effects on our cells ‘ normal maps such as grow and distinction. Nevertheless, aging and familial factors can besides lend to the addition of homocysteine degree. However, urban life style can do the lift of homocysteine in our organic structure such as inordinate ingestion of java and intoxicant which had been proven that they might increase the homocysteine degrees ( De Bree A et Al 2002 ) . Dietary consumption does play a portion to impact homocysteine degrees. For case, ruddy meat, has been proven to promote blood degrees of homocysteine. Similarly, malnutrition of vitamin B may besides promote homocysteine degrees ( Devlin TM, 2002 ) . & lt ; hypertext transfer protocol: //www.lef.org/protocols/heart_circulatory/homocysteine_reduction_01.htm & gt ; .

Surveies had proven that lift of homocysteine is strongly related to cardiovascular diseases such as myocardial infarction, shot, peripheral vascular disease, increased hazard of premature coronary arteria disease and thromboembolism. Imbalance of homocysteine degrees contribute to atherosclerosis in three ways:

1. toxic that amendss the intima
2. intervention with coagulating factors, and
3. oxidization of low-density lipoproteins ( LDL ) .

Endothelial disfunction and hurt, which so followed by thrombocyte activation and thrombosis might be the mechanisms that consequence cardiovascular diseases. Homocysteine will bring forth cytotoxic on endothelial cells, which is finally a production of reactive O species ( ROS ) ( Blundell et al. 1996 ) , impaired production of endothelium-derived azotic oxide and harm to the endothelial cells ( Stamler et al. 1993, Tawakol et Al. 1997 ) , and proliferation of smooth musculus cells. ( Tsai et al. 1994 ) Lipid peroxidation and LDL oxidization are increased by homocysteine which will take to atherosclerosis, but this is non yet been clinically proven in all the surveies ( Blom et al. 1992, Halvorsen et Al. 1996 ) . On the other manus, formation of free O species or ROS can finally damage to the vascular, proliferation of smooth-muscle cells, alterations of endothelial cell map and construction ( Welch & A ; Loscalzo 1998 ) . But, there is another account by some of the research workers, after tissue harm, homocysteine degree will be increased, which in bend further doing the endothelial cell to be damaged. An increased homocysteine degree would be a good indicant that shows tissue harm and therefore promotes redness and thickener of vascular harm. ( Dudman 1999 ) Research from a Finnish agrees that the likeliness that homocysteine is really a consequence instead than a factor of vascular harm ( Knekt et al. 2001 ) . Some epidemiological surveies have proved that small sum of blood vitamin Bc and B6 vitamin concentrations increase the opportunities for acquiring vascular diseases, and the addition blood tHcy would be an index of the low vitamin concentrations ( Folsom et al. 1998, Robinson et Al. 1998, Rimm et Al. 1998 ) . Furthermore, a survey showed that by comparing 131 patients with terrible obstructions in two coronary arterias, the moderate obstruction of one coronary arteria was 88 patients, and without bosom disease was the another group of healthy persons. The research workers discovered a relationship between blood homocysteine degrees and badness of the coronary obstructions, for every increasing of homocystein by 10 % , every bit, there will be a rise of hazard of developing coronary bosom disease. Furthermore, postmenopausal adult females with increased homocysteine degrees had a higher chance of developing coronary bosom disease. Besides, survey proved that homocysteine degrees were much higher in people who developed vein coagulums than in similar people who did non. The tabular array below shows the mention values of blood homocysteine for both male and female.

To mensurate serum homocysteine degrees blood is drawn after a 12-hour fast.

The relationship between homocysteine and cardiovascular disease was discovered about 25 old ages ago from the observation of people with a rare status called homocystinuria. They are more likely to hold terrible and serious cardiovascular disease during adolescent period. This is likely due to the enzyme lack which in bend causes accretion of the homocysteine in the blood and excreted out by micturition. Increased of the homocysteine degree is linked to 10 % ~ 20 % of the coronary bosom disease. ( Stephen Barrett, M.D, 29th March 2003 ) . Hyperhomocysteinemia may do narrowing and hardening of the arterias which medically known as coronary artery disease. Atherosclerosis is believed to go on by a broad scope of ways including addition of blood homocysteine. Changes in the blood vas construction will interrupt blood flow. Hyperhomocysteinemia may besides do the inclination of inordinate blood curdling. Thrombus will be formed within the blood vas which is called thrombosis which farther disrupt the blood flow. As a consequence, there is a deficiency of blood supply to the bosom musculuss and as a consequence bosom onslaughts occur, same thing goes to the encephalon which so causes shot. Increase of blood homocysteine degrees have been proved to be closely related with formation of blood coagulums in venas which are deep vena thrombosis ( DVT ) and pneumonic intercalation. The mechanism which involves in this procedure is instead complicated. Surveies have proved that even a reasonably high degrees of homocysteine degree will hold a higher perennial incidence of blood coagulum formation ( Siamak Nabili, MD, MPH )

From the position of cardiovascular diseases, there is a closely relationship with smoke. People pattern smoking tend to develop cardiovascular disease easier than non- tobacco users. Therefore, there was a survey conducted by The Adelaide and Meath Hospital Dublin, integrating the National Childrens Hospital and Trinity College, Dublin, Ireland in 19 states in Europe with a control group of less than 60 years-old people and matched with age and gender had showed that non-smoker had a lower blood homocystein degree than the tobacco users. The statistic showed that tobacco user with a homocystein degree which is about above 12µmol.l-1 will hold a higher opportunity of acquiring cardiovascular disease which is a really contrast with the non-smokers but with a normal degree of blood homocystein. The more one smokes the higher the degree of homocysteine in our organic structure. ( European Heart Journal, 23rd 2002 ) Exposure to smoke really has an inauspicious and lay waste toing consequence on the folic acid degree. Folic acid is a cofactor to help demethylation of homocysteine to non toxic methionine. Hence, smoke will ensue an increased of homocysteine degree. Homocysteine is usually changed into other acids to be used by the our organic structure cells. If the homocysteine degree is beyond the mention scope, there could be non adequate B vitamins to assist the organic structure to catabolize the homocysteine. For those people who lack of vitamin Bc, vitamin B12 and vitamin B6 in their diet will finally promote their homocyseteine degree. Some other factors that can increase the homocysteine degree include low degrees of thyroid endocrine, kidney disease, psoriasis or even aging.

Once negotiations about cut down plasma homocysteine degree, we should ever travel back to the metamorphosis procedure of homocyteine or the methionine rhythm. Vitamin B6, B12 and folic acid really play a important function in the homocysteine metamorphosis. From at that place, they are somehow associate with the reduction of homocysteine degree. Harmonizing to & lt ; hypertext transfer protocol: //www.quackwatch.com/03HealthPromotion/homocysteine.html & gt ; dietetic merchandises with folic acid can diminish homocysteine degrees among most of the patients. Normally, 1 mg/day of folic acid is adequate for curative intent. However, when it is uneffective, Vitamins B6 and B12 can be added together with the folic acid, which should be invariably consumed. Some of the doctors do urge that patients with coronary artery disease to devour Vitamin B without being tested to happen out whether it is utile to cut down the homocysteine degree. A research which conducted with 80,000 adult females for 14 old ages showed that the hazard of acquiring bosom onslaughts was lowest among for those who take in multivitamins, folic acid and B6. Besides, there was a research involved with 101 work forces with vascular disease were given folic acid, B6, and B12 addendums. There was a lessening in the sum of carortid plaque in their arterias by ultrasound scrutinies. Folate and Vitamin B12 may assist to change over homocysteine back to a less harmful substance- methionine. Folate can be synthesized in the bowel by devouring more fiber merchandises every bit good. Food beginnings of vitamin Bc include garbanzos, Spinacia oleracea, almonds, walnuts, egg, fruits. Beginnings of vitamin B12 include salmon, trout, lamb, egg, beef, tuna, cheese and poulet ECT. Folic acid and other B Vitamins aid catabolise homocysteine in the organic structure. Vitamin B, vitamin Bc, B12, and B6 may help in the converting of homocystein back into cysteine and methionine. Thus, deficiency of B vitamins in the organic structure can really interrupt the metamorphosis homocysteine which in bend addition its degree in the blood. Intima bed of blood vass really can be affected or damaged by homocyestein, which can advance blood thrombosis and therefore coronary artery disease as a consequence.

In a nutshell, homocysteine is really an amino acid which will be produced mundane by our organic structure metamorphosis. A balance of homocysteine will non hold an adversely consequence on our organic structure macroscopic and microscopic major maps. Well, a malnutrition or instability homocysteine sum in blood will take to wellness issues be it hyperhomocysteinemia or hypohomocysteinemia. A good pattern of life style can really forestall the increased degree of homocysteine in our blood to avoid unneeded to be happened. However, if a individual is diagnosed with the symptom of hyperhomocysteinemic, he can really devour a changeless and lasting folic acid, Vitamin B6 and B12 in order to command a good homocysteine metamorphosis which in bend to lower homocysteinemia degree and prevent it traveling to be increased following clip.