Amino Acids

Referred to as the ‘building blocks of life’, amino acids make up proteins in every tissue of the body, and play a major role in nearly every chemical process that affects physical and mental function. Amino acid deficiencies may manifest as fatigue, allergic sensitivity, arthritis, digestive disorder, cognitive function, weakened cardiovascular health, decreased athletic performance and neurologic imbalance. DirectLabs offers a range of tests to help you determine your specific amino acid levels.

Homocysteine

Heard of Homocysteine?

If not, you will soon, health experts say. New research is finding Homocysteine (ho-mo-SIS-teen), an amino acid, may play a role in the onset of dementia. The good news is that vitamins B6, B12 and folic acid may reduce the levels of Homocysteine in the blood, says Dr. James Toole, a professor of neurology and public health science at Wake Forest University School of Medicine.

He believes people will soon have their Homocysteine levels checked as routinely as cholesterol. “Researchers have found high Homocysteine levels are associated with Alzheimer’s disease and brain atrophy,” Toole says. “This is big time news.”

The latest research appears in the May 29 issue of the journal Neurology. Two studies show that people with elevated levels of Homocysteine are more likely to have brain atrophy and vascular disease, which are related to the development of dementia. Alzheimer’s disease is one form of dementia. In one of the studies, researchers tested the blood Homocysteine levels of 36 healthy, elderly people, and then used brain scans to measure the amount of brain atrophy, or loss of brain cells and volume. The study found those who had the highest levels of brain atrophy were twice as likely to have high Homocysteine levels as those with less atrophy. Previous research has shown mild elevations of Homocysteine in about 5 percent to 7 percent of the population, says Toole, who wrote an editorial in the journal on the research.

In the second study, researchers did similar tests on 43 people with Alzheimer’s and 37 healthy people. They found people with high Homocysteine levels were 10 times more likely to have vascular disease. The study also found Alzheimer’s patients were 12 times more likely to have low levels of vitamin B6 than the healthy people. “The finding will need to be confirmed by other studies, but it is interesting,” says Joshua W. Miller, author of the second study and an assistant professor of medical pathology at University of California, Davis Medical Center. “Vitamin B6 has been shown to play a role in brain function and memory, so it’s possible that taking B6 supplements could help Alzheimer’s patients.”

Earlier studies have linked Alzheimer’s and elevated Homocysteine, Miller says. His research didn’t find that same correlation, but in studies that did find a link, the dementia attributed to Alzheimer’s could be made worse by vascular disease. Homocysteine is an amino acid that’s formed when the body breaks down methionine, which is found in protein-rich foods, Miller says. Previous research has found folic acid counteracts the Homocysteine by converting it into a non-toxic form. However, in people who don’t have enough folic acid, the level of Homocysteine rises and becomes toxic.

Homocysteine is suspected of irritating the lining of blood vessels, accelerating atherosclerosis and contributing to blockages, Toole says. If folic acid – also known as folate – keeps Homocysteine down, shouldn’t everyone take a supplement? Not exactly, Toole says. Folic acid deficiencies have been linked to certain birth defects. In 1998, the U.S. Food and Drug Administration mandated that grain producers fortify their product with folic acid. That means that bread, cereals and pastas – anything made with grain – contain added folic acid, Toole says. So, it’s very possible you get plenty of folic acid by eating a balanced diet.

Also, no one has established the optimum level of folic acid people need. So theoretically, you could take too much, Toole says. Vitamins B12 and B6 may also lower Homocysteine levels, Miller says. In addition to grains, citrus fruits, tomatoes and vegetables are good sources of folic acid. You can get vitamin B6 from meat, poultry, fish, fruits, vegetables and grain products. Major sources of B12 include meat, poultry, fish and milk, Toole says. Toole does recommend that everyone over age 60, or people at high risk of heart and vascular disease, ask to have their Homocysteine levels checked by their doctor. This can be done with a simple blood test.

Homocysteine Lab Test Information

Homocysteine (pronounced homo-SIS-teen) is an amino acid and is found normally in the body. Its metabolism is linked to that of several vitamins, especially folic acid, B6, and B12. Deficiencies of those vitamins may cause elevated levels of Homocysteine.

Homocysteine is a building block for the production of proteins in the body. However, elevated levels of Homocysteine are associated with premature vascular disease. Studies have shown that increased homocysteine levels can dramatically increase your risk of heart disease, stroke, peripheral vascular disease and clotting disorders. Fortunately, high homocysteine levels may be reduced with dietary vitamins folate, B6 and B12. High homocysteine levels are seen in renal disease, heart failure, and B12 or folate deficiency. Homocysteine levels also tend to increase with age. Low levels are associated with diets high in fruits and vegetables (especially those high in B vitamin and folate). An ideal homocysteine levels is less than 9 micromol/liter.

In recent years, studies have accumulated suggesting that a high level of homocysteine increases a person’s chance of developing heart disease, stroke, and peripheral vascular disease (a reduced blood flow to the hands and feet).

In September 1995, the National Heart, Lung, and Blood Institute (NHLBI) convened a special panel to review the scientific evidence about homocysteine’s possible link to heart disease. The information that follows is based on the panel’s conclusions.

Briefly, the panel said that an elevated homocysteine level appears to increase the risk of heart disease, stroke, and peripheral vascular disease. However, no studies have been done to show that lowering the homocysteine level reduces the risk of heart disease. The panel stressed that more research, especially a clinical trial, must be done to understand the possible association between the level of homocysteine and heart and related diseases.

Homocysteine & Heart Disease

Various studies have found that persons with elevated levels of homocysteine in their blood are at an increased risk of heart and vessel disease. These studies include the Physicians’

Health Study, the Tromso Study from Norway, the Framingham Heart Study, and a meta-analysis of nearly 40 studies. Some studies indicate that persons with elevated homocysteine levels tend to also have other risk factors for heart disease, especially smoking, high blood pressure, and high blood cholesterol.

So far, no clinical trial has been done to show that lowering homocysteine levels alters the progression of heart disease, or prevents heart attacks or strokes.

Why Homocysteine?

Much more basic research must be done before scientists understand how an elevated homocysteine level affects the development and progression of heart disease. However, scientists have several theories: First, a high level of homocysteine may be involved with the process called atherosclerosis, the gradual buildup of fatty substances in arteries.

Homocysteine also may make blood more likely to clot by increasing the stickiness of blood platelets. Clots can block blood flow, causing a heart attack or stroke. Increased homocysteine may affect other substances involved in clotting too. Finally, higher homocysteine levels may make blood vessels less flexible–and so less able to widen to increase blood flow. However, none of theories has so far been proven.

What Determines Homocysteine Levels?

Individuals differ in their levels of homocysteine. Two key factors affect a person’s homocysteine level–genetics and environment.

Genetics

Genetic factors help regulate the level of homocysteine in the blood. For instance, genetic flaws (mutations) can affect homocysteine’s metabolism. The NHLBI Family Heart Study found families with genetic mutations in the enzymes involved in homocysteine metabolism.

The NHLBI Framingham Heart Study and other investigations have found a relationship between elevated homocysteine levels and families with early heart disease.

Environment
The level of homocysteine in the blood also is affected by the consumption of vitamins, especially folic acid, B6, and B12.

Data from the Framingham Heart Study show that only 30-40 percent of the population was getting 200 or more micrograms of folic acid in their diet. The data indicated that for many persons an intake of at least 400 micrograms was needed to keep homocysteine levels from becoming elevated.

Data also indicate that homocysteine levels are higher in older persons than younger ones and in women after menopause than in those before. But more research is needed to confirm and explain these differences.

R-Group

In solution it is the nature of the amino acid R-groups that dictate structure-function relationships of peptides and proteins. The hydrophobic amino acids will generally be encountered in the interior of proteins shielded from direct contact with water. Conversely, the hydrophilic amino acids are generally found on the exterior of proteins as well as in the active centers of enzymatically active proteins. Indeed, it is the very nature of certain amino acid R-groups that allow enzyme reactions to occur.
The imidazole ring of histidine allows it to act as either a proton donor or acceptor at physiological pH. Hence, it is frequently found in the reactive center of enzymes. Equally important is the ability of histidines in hemoglobin to buffer the H+ ions from carbonic acid ionization in red blood cells. It is this property of hemoglobin that allows it to exchange O2 and CO2 at the tissues or lungs, respectively.

The primary alcohol of serine and threonine as well as the thiol (-SH) of cysteine allow these amino acids to act as nucleophiles during enzymatic catalysis. Additionally, the thiol of cysteine is able to form a disulfide bond with other cysteines: Cysteine-SH + HS-Cysteine <——–> Cysteine-S-S-Cysteine This simple disulfide is identified as cystine. The formation of disulfide bonds between cysteines present within proteins is important to the formation of active structural domains in a large number of proteins. Disulfide bonding between cysteines in different polypeptide chains of oligomeric proteins plays a crucial role in ordering the structure of complex proteins, e.g. the insulin receptor.

The Peptide Bond.

Peptide bond formation is a condensation reaction leading to the polymerization of amino acids into peptides and proteins. Peptides are small consisting of few amino acids. A number of hormones and neurotransmitters are peptides. Additionally, several antibiotics and antitumor agents are peptides. Proteins are polypeptides of greatly divergent length. The simplest peptide, a dipeptide, contains a single peptide bond formed by the condensation of the carboxyl group of one amino acidwith the amino group of the second with the concomitant elimination of water. The presence of the carbonyl group in a peptide bond allows electron resonance stabilization to occur such that the peptide bond exhibits rigidity not unlike the typical -C=C- double bond. The peptide bond is, therefore, said to have partial double-bond character.

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Optical Properties of the Amino Acids

A tetrahedral carbon atom with 4 distinct constituents is said to be chiral. The one amino acid not exhibiting chirality is glycine since it’s ‘”R-group” is a hydrogen atom. Chirality describes the handedness of a molecule that is observable by the ability of a molecule to rotate the plane of polarized light either to the right (dextrorotatory) or to the left (levorotatory). All of the amino acids in proteins exhibit the same absolute steric configuration as L-glyceraldehyde. Therefore, they are all L-a-amino acids. D-amino acids are never found in proteins, although they exist in nature. D-amino acids are often found in polypeptide antibiotics.

The aromatic R-groups in amino acids absorb ultraviolet light with an absorbance maximum in the range of 280nm. The ability of proteins to absorb ultraviolet light is predominantly due to the presence of the tryptophan which strongly absorbs ultraviolet light.