Irish Pauline L. Ereno Lorenzos Oil 1. What is ALD?

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Adrenoleukodystrophy is a rare, basically ignored genetic demyelinating disease that shows symptoms between the ages 5 and 12. A diagnosis of ALD was equivalent to a death sentence; typically death ensued within a few years. ALD is one of eight leukodystrophies, inheritable metabolic diseases that lead to the destruction of the myelin, a complex fatty neural tissue that insulates many nerves of the central and peripheral nervous systems. Without functional myelin, nerves are unable to aid in the conduction of an impulse, which leads to increasing disability. The disorder is also a recessive X-linked genetic mutation, meaning that the trait is carried on the X chromosome. As a result of X-linkage, the disease only affects males. Affected men do not live long enough to pass the gene on to their offspring. Since females pass on the sole X chromosome obtained by male offspring, the trait has to be inherited from the mother. This sequence of events appears to be related to an abnormal accumulation of saturated very-long-chain fatty acids (VLCFA) in the serum and tissues of the central nervous system, which sets off an abnormal immune response that leads to demyelination. It is unclear exactly how this chain of events works, but scientists do know that it has its roots in genetics. 2. How does ALD affect the patients? ALD only affects males. It is characterized by an inflammatory process that destroys the myelin, causing relentless progressive deterioration to a vegetative state or death, usually within five years. Affected men do not live long enough to pass the gene on to their offspring. Since females pass on the sole X chromosome obtained by male offspring, the trait has to be inherited from the mother. The single gene mutation responsible for this disease is found at locus Xq28. This gene mutation causes the production of a malfunctioning transporter protein found in peroxisomes, an entity within cells responsible for breaking down long chain fatty acids. Without the use of this protein, the enzyme very long chain fatty acid CoA synthetase cannot pass into the peroxisomes. In ALD, these VLCSFAs build up in the blood stream up to 2-4 times higher than normal. VLCSFAs are dangerous due to their properties. In the absence of this enzyme, very long chain saturated fatty acids (VLCSFAs) that are shipped into peroxisomes cannot be broken down. VLCSFAs are fatty acids that do not contain carbon-carbon double bonds and are 24 or 26 carbon molecules in length. An inability to break down VLCSFAs leads to their accumulation within the body, particularly within the white matter of the central nervous system, adrenal gland, and leukocytes (blood cells) . 3. Symptoms of people with ALD Symptoms often appear in boys between the ages of 4 and 8 which may include behavioral changes, crossed eyes, hyperactivity, moodiness, inability to understand verbal communication, forgetfulness, difficulty at school, detoriation of handwriting, decreased fine motor control, seizure, coma and muscle spasms. Other severe symptoms are blindness, hearing loss, paralysis, inability to speak, and dementia.

4. Is the disease physically limiting? Explain Yes, because as the brain function declines and the protective myelin sheath is gradually stripped from the brains nerve cells, the neurons will not conduct any action potentials anymore. They will soon stop telling the muscles and other elements of the central nervous system what to do, making the patient paralyzed or unable to move. 5. If you were the parents of the patient, would you also do what the parents did to help their child? To what extent? Yes, I would. As a parent, I would probably feel the same way too if I see my child like that. I will help my child by doing my best in learning more about ALD, studying its cause and effects and the probable medicines that I can give to my child to help them recover. I will show my love and support to them by always being there for them. I will never let them get hurt or feel neglected or useless. I will never give up to bring my son back to me. Many people believe that science is merely for scientists and doctors, but in reality, anyone can act or think in a certain manner to reach the desired answers. It takes coordination, determination, and cooperation. You ask all the questions you can think of and then use the answers you find to those questions to ask more. 6. How do they cure the disease? Draw and name of the structural formula of the compound

In the first attempt to cure Lorenzo, the Odones created a diet low in VLCSFAs to combat accumulation. However, his body continued to synthesize VLCSFAs. In order to halt demyelinization, it was necessary to impede VLCSFA synthesis. The Odones came upon a paper stating that an increase in the presence of oleic acid, a short chain unsaturated fatty acid, leads to a decrease in VLCSFA levels. With this knowledge, Augusto determined that the synthesis of very long chain unsaturated fatty acids are in competition with the synthesis of VLCSFAs. Both synthesis mechanisms compete for the use of a single enzyme. Increasing the amounts of unsaturated fatty acids available for synthesis allows for the synthesis of unsaturated fatty acids to out compete the synthesis of VLCSFAs. Interestingly, the damage to myelin is done specifically by saturated fatty acids. Unsaturated fatty acids, fatty acids that contain carbon-carbon double bonds, are not deleterious to myelin and therefore do not cause the development of ALD. The mixture of oleic acid and euric acid, another short chain unsaturated fatty acid, is referred to as Lorenzo's Oil 7. Through illustration, how do these cures help in prolonging the patient's life?

If they fed Lorenzo the unsaturated fatty acid oleic acid, then his enzyme would use oleic acid instead of equivalent saturated fatty acids to elongate into very long chain fatty acids. This is the concept of competitive inhibition (contrast it with noncompetitive or uncompetitive inhibition). There is even a dramatic point in the movie where Peter Ustinov (playing a physician) says: "This is competitive inhibition!" The use of oleic acid lowered Lorenzo's blood VLCFA but, after 3 months, the level was still twice normal. That is, the enzyme at the endoplasmic reticulum can still pick up or utilize saturated fatty acids and add two carbon units to make VLCSFAs. A stronger competitive inhibitor was needed. Erucic

acid was chosen; it is a very long chain (22 carbons long) unsaturated fatty acid that is used by the enzyme to make longer harmless unsaturated fatty acids. With both erucic acid and oleic acid present, saturated fatty acids are not able to bind to the active site of the enzyme and are not elongated. Erucic acid may be more effective than oleic acid because of its longer chain length (it may bind to the enzyme with an affinity higher than the shorter oleic acid). It successfully lowered Lorenzo's VLCSFAs to normal levels 8. How do carboxylic acids related to physiological function of humans? What is the relevance of carboxylic acid to biomolecules? Carboxylic acids are organic and found in many organic substances such as carbohydrates. Carbohydrates are important because they're where living things get most of their energy from. Most of the carbohydrates you consume will ultimately be broken down into glucose. Glucose is a simple sugar that acts as the most important metabolic fuel for most living cells. Carbohydrates provide the chief energy source to higher organisms. Carbohydrates are broken down into pyruvic acid through the glycolytic pathway thereby releasing energy. This molecule sustains life.