| Amino Acids |
| Carbohydrates |
| Proteins | Lipids | |
| Nucleotides | Vitamins | |
| Molecular Genetics | Metabolic Cycles |
Many of the following sites require the CHIME browser plugin which you can download for free from MDL Information Systems. You will have to register with MDL, but it's free. Some of the tutorials use SCHOCKWAVE or AUTHORWARE and you will need the free players from Macromedia to view them.
Let me know if you have a link you think I should add. tfrick@nwhealth.edu
A number of serious disorders are caused by improper amino acid metabolism. In class we discussed phenylketonuria which results from the inability to convert phenylalanine into tyrosine. Alkaptonuria is another disorder that occurrs later in the phenylalanine/tyrosine metabolic pathway. Alkapronurea was the first inborn metabolic error to be recognized; it results in the excretion of black pigments in the urine. These pigments also accumulate in tissues. When the pigments accumulate in collagen, they cause ochronosis which can result in degenerative arthritis. A defect in the metabolic pathway of branched chain amino acids causes maple syrup urine disease. In addition to the peculiar maple syrup smell of the urine, this disorder causes mental retardation and other neurological disorders which can be fatal.
Amino acid disorders can also occur if a person is unable to get balanced protein in their diet. Malnutrition has many causes; inadequate protein, vitamins, fatty acids, or minerals. Protein malnutrition is broken into two major categories: Marasmus and Kwashiorkor. Marasmus occurs when a person has inadequate protein and calories in their diet. The emaciated 'walking skeletons' you have probably seen in news stories of famine in the Sudan are suffering from marasmus. Kwashiorkor results from a diet which is adequate in calories, but deficient in protein. Children with this condition often have round bellies and, at first, appear well fed. The roundness is actually edema and the victims are starving to death. Although these disorders are rare in the developed countries of the world, lifestyle choices can result in similar problems. Strict vegitarians must be careful to balance their diets with legumes (which are deficient in methionine) and grains (which are limiting in lysine).
One last amino acid deficiency disorder has a totally different cause. Goiter is caused by deficiency of the amino acid hormone, thyroxine. The most common cause of goiter is a dietary deficiency of iodine. The body needs iodine in order to synthesize thyroid hormone (thyroxine) from tyrosine. Iodine deficiency is now rare in the developed world, but, goiter may still develop due to an inborn error in thyroxine synthesis. In goiter patients, the thyroid gland can grow to bizarre size in its futile attempt to synthesize thyroxine.
Purines that are not salvaged for reuse are converted to uric acid which is excreted. Unfortunately, uric acid is not very soluble and, when it is produced faster than it is excreted, it can accumulate in tissues to a concentration where it begins to crystallize. Gout, a common form of arthritis, results from inflammation triggered by diposition of uric acid crystals in joint tissues. Arthritides will bring many patients to your chiropractic practice: to develop an effective treatment plan you must keep in mind what the underlying problem is. Most of the effective treatments for gout are pharmacologic in nature.
Lesch-Nyhan Syndrome is a serious disease that affects children who have a faulty enzyme in the purine salvage pathway. Lip biting, head banging and other self-mutilating behaviors are classic symptoms of Lesch-Nyhan Syndrome. They may be the child's irrational response to the unbearable pain due to high levels of uric acid in their tissues. There is more to the disease than severe gouty symptoms, however, because neurological disorders and mild to severe mental retardation are also common symptoms. The cause of these clinical symptoms is not understood. Some physicians are hopeful that the relatively simple biochemical problem which results in these complex clinical presentations may allow development of an effective treatment.
One final defect in purine metabolism is adenosine deaminase (ADA) deficiency : one of the causes of severe combined immunodeficiency disease (SCID). ADA catalyzes an early reaction in the breakdown and recycle pathways for adenine nucleotides. In ADA deficiency, the adenine nucleotides accumulate (principally AMP and cAMP). These compounds are powerful metabolic regulators which cause havoc when they cannot be degraded. ADA deficient patients do not develop any immunocopmetent cells. They must be raised in a sterile "bubble" or they will die from fatal infections in infancy. The simple biochemical problem has made gene therapy for this type of SCID possible.
The potential of gene therapies to treat all sorts of genetic disorders is exciting, but one must always keep in mind that no intervention is without risk. The death of Jesse Gelsinger is a grim reminder of that.
Another area where the genetics revolution will impact health care is early diagnosis of genetic disorders and genetic counseling for those at risk of developing genetically linked disorders. The CDC has a nice Grand Rounds Webcast discussion of this topic. Information on where and how to get genetic testing is also readily available.
