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Stimulation of the sympathetic nervous system results in A. B. C. D. E. dilation of the pupils. increase in heart rate. constriction of the bronchi. inhibition of the digestive system. all but C. Where are we? Last time I discussed... homeostasis, the mechanisms the body uses to maintain stability of the internal milieu. allostasis, the mechanisms the body uses to switch from the "rest and digest" mode to the "fight or flight" mode. I also discussed why too much stress is harmful. This time I will discuss... how too much sugar and oxygen speed up senescence (aging). Sugar, Oxygen and Aging There are many causes of aging, including genetic, environmental and nutritional. I am going to discuss two factors: sugar and oxygen, two things we surely can't live without; and in many cases, two things that may accelerate dying. Too much of a good thing is not necessarily a good thing. The Maillard Reaction Louis Camille Maillard (1912) was a French physician and chemist who, after studying the chemical reactions that led to the color of urine, was trying to figure out how amino acids bonded together to form proteins. In doing so he heated amino acids with sugars (which he used as a dehydrating agent) and noticed that a non-enzymatic browning reaction occurred serendipitously. He suggested that the reaction might take place in the human body, and he even imagined the critical role we now know it plays in diabetes. Food Science and the Maillard Reaction Food scientists studied the Maillard reaction; first to understand production of the horrible flavors that occurred in the powdered eggs eaten by GIs during WWII, and later to learn how it improves the color, aroma and flavor of cooked foods. Colors of toast, beer, coffee, chocolate and maple syrup are due to Maillard reaction. Aromas of bread, popcorn, tortillas and aromatic rice are due to the Maillard reaction. Flavors of browned or roasted beef are due to the Maillard reaction. Still, the biologists ignored Maillard's work until 1968. Maillard Reaction: Color Maillard Reaction: Aromas Maillard Reaction: Flavor The Maillard Reaction Occurs In Mixtures of Proteins and Sugars Albumen (mixture of white proteins) that makes up the
egg white was used to make photographic prints. The browning of the albumin is due to the Maillard reaction.
The Maillard Reaction Gives the Brown Color to Humus in the Soil Samuel Rahbar
Samuel Rahbar (1960s) serendipitously found, while searching for mutations in the hemoglobin molecule in the ethnically diverse population of Iran, that diabetics had glucose attached to their hemoglobin. Enzymatic vs. Non-Enzymatic Reactions
Up until now, I have emphasized how important enzymes are in catalyzing a diverse array of chemical reactions in the body. Enzymatic reactions have the advantage of being controlled and controllable. But just because most reactions are catalyzed by enzymes, it does not mean that nonenzymatic reactions can't also occur in the body. Enzymatic vs Non-Enzymatic Reactions
Until Rahbar discovered glycation (non enzymatic addition of glucose) of hemoglobin in diabetics, biologists had ignored the Maillard reaction, thinking that the nonenzymatic addition of glucose to the aminocontaining groups of proteins required the high temperature attained while cooking, not the low temperatures found in the human body. Besides, it was already known that biological systems used enzymes to put sugars on proteins, a process known as glycosylation. The Maillard Reaction Can Affect Many Proteins Rahbar's discovery of glycated hemoglobin changed our way of thinking. Soon it was discovered that many proteins can participate in the Maillard Reaction. Advanced Glycation Endpoint (AGE) The Maillard Reaction can occur with any protein if there is too much sugar around. A long lived protein, like the protein that makes up the lens of the eyes, can bind many sugars. The glycated protein is further attacked by other glucose molecules. Such proteins are called, "advanced glycation end products" (AGEs). AGEs can crosslink to other AGEs and form networks of glycated proteins. The formation and crosslinking of AGEs is enhanced by free radicals. Correlation of AGEs with Aging and Disease AGEs accumulate with age. Because of their elevated blood sugar, diabetic people accumulate AGEs earlier in life. Depending where AGEs occur, they can cause impaired function of that organ. The buildup of AGEs is correlated with kidney disease, eye damage, heart disease, atherosclerosis, nerve damage and Alzheimer's disease. The A1c Now Monitor Measures Glycated Hemoglobin Pyridorin (pyridoxamine), a member of the vitamin B6 family, blocks AGE formation. This and other inhibitors of the Maillard reaction may soon be available as medications. Joseph Priestley
Joseph Priestley discovered that we need oxygen to live and plants produce that oxygen. He also suggested that too much oxygen may be detrimental. Joseph Priestley Tried the Pure Air He Produced on Himself
"The feeling of it to my lungs was not sensibly different from that of common air; but I fancied that my breast felt particularly light and easy for some time afterwards. Who can tell but that, in time, this pure air may become a fashionable article in luxury....From the greater strength and vivacity of the flame of a candle, in this pure air, it may be conjectured, that it might be particularly salutary to the lungs in certain morbid cases, when the common air would not be sufficient to carry off the putrid effluvium fast enough." Oxygen Bars: You Can Sell Anything Oxygen Bars: Rent Them for Parties Joseph Priestley: A moralist
"But, perhaps, we may also infer from these experiments, that though pure dephlogisticated air [oxygen] might be very useful as a medicine, it might not be so proper for us in the usual healthy state of the body; for, as a candle burns out much faster in dephlogisticated than in common air, so we might, as my be said, live out too fast and the animal powers be too soon exhausted in this pure kind of air. A moralist, at least, may say, that the air which nature has provided for us is as good as we deserve." Free Radicals Oxygen is typically reduced to oxygen dihydride (water) at the end of the respiratory chain in the mitochondria. Some of the oxygen is partially reduced to form superoxide by the electron transport chain. Superoxide is a free radical. A free radical is a chemical with an unpaired electron. Free radicals are very reactive because electrons like to pair up to form stable twoelectron bonds in uncontrolled non-enzymatic reactions. The Production of Superoxide Starts a Chain Reaction
O2 + 4H+ + 4e- 2H20 (>95% of the time) 2O2.- (<5% of the time) When the oxygen becomes a free radical, it steals an electron from another molecule in the cell. The electron donating molecule is then left with an unpaired electron, causing it to become a free radical too. Thus a selfperpetuating chain reaction occurs where the structure and function of many molecules can be altered very rapidly. Superoxide Can Enter Our Lungs from Cigarette Smoke
Superoxide and other free radicals also occur in cigarette smoke. Oxidative Damage
The free radicals formed by the electron transport chain and cigarette smoke can cause oxidative damage to: Lipids in the cell membrane which causes leakage into and out of cells. Proteins, leading to loss of enzyme activity. DNA, leading to mutations. Theory of Aging
Aging and its associated diseases may result, in part, from the accumulated changes that happen to molecules and cells that are initiated by glucose and free radicals. Albert Szent-Gyorgyi thought that antioxidants were important for good health, but was ignored Addison's Disease and Browning Szent-Gyorgyi was interested in the function of the cortex of the adrenal gland. Addison's disease is a malfunction in the adrenal gland and a patient's skin becomes brown before the person dies of the disease. Szent-Gyorgyi realized that a similar browning reaction occurs with certain fruits and vegetables, like apples, bananas and potatoes. Szent-Gyorgyi was convinced that there are in biological mechanisms. So he set out to study the browning reaction in the potato. He did this in the hope of discovering the key to the understanding of adrenal function. principle no fundamental differences between animals and plants when it comes to basic A Dead End Szent-Gyorgyi showed that potatoes contain polyphenol and polyphenol oxidase. The enzyme oxidizes polyphenol to quinone with the help of oxygen. In an undamaged potato, the quinone is reduced back again with electrons made available from the electron transport chain, and the potato is white. In a damaged potato, reduction of quinone cannot keep pace with the rapid oxidation of the phenol. The quinones remain unreduced and form brown pigments. However, this system was a dead end and gave him no information about adrenal function. Peroxide and Benzidine Blue So Szent-Gyorgyi turned to plants like turnip and cabbage, which do not turn brown when they are bruised. These plants contain a peroxidase, which inactivates peroxide. In the presence of this enzyme, peroxide can oxidize aromatic substances to brown pigments. If benzidine is added to a peroxide in the presence of peroxidase, a deep-blue color appears immediately, which is caused by the oxidation of the benzidine. Discovery of a New Reducing Substance If he used some juice which had been squeezed from the plant instead of a purified peroxidase, and added benzidine and peroxide, the blue pigment appeared, but only after a small delay of about a second. Analysis of this delay showed that it was due to the presence of a reducing substance, which reduced the oxidized benzidine again, until the reducing substance had itself been used up. "There was great excitement in my little basement room in Groningen, when I found that the adrenal cortex contained a similar reducing substance in relatively large quantities." The Substance was a Carbohydrate
Szent-Gyorgyi isolated the substance in question from adrenal glands and plants. He showed that it had the formula C6H8O6 and was thus related to the carbohydrates. He called it ignose, then godnose. He accepted the editor's proposed moniker "hexuronic acid" since it was a six carbon sugar acid. Szent-Gyorgyi found that hexuronic acid could not replace the adrenals, but it did cause the disappearance of pigmentation in patients with Addison's disease. More importantly, he discovered that hexuronic acid prevented unwanted oxidations and was the vitamin that prevented scurvy. He renamed it ascorbic acid for its antiscorbutic activity. Szent Gyorgyi suggested that vitamin C and other antioxidants should be very important in human health since they could neutralize free radicals. Szent-Gyorgyi Discovered Vitamin C, because he was aware of a 1 sec time lag.
Discovery consists of looking at the same thing as everyone else and thinking something different. Albert Szent-Gyorgyi (1962) Antioxidant Protection Antioxidants, including vitamins A, C and E neutralize free radicals by donating one of their own electrons, ending the "electron-stealing" reaction. Antioxidants do not become free radicals in the process because they remain stable after donating an electron. Antioxidants and Commercial Products neimanmarcus.com FDA Labeling Guidelines for Cosmetics Nuskin Science of Aging Cure for Aging?
The U.S. Food and Drug Administration recommends consuming many fruits and vegetables. They believe that a diet rich in fruits and vegetables is more effective than supplements because each fruit and vegetable has hundreds of phytochemicals. The protection from disease is likely a result of a combination rather than any single factor. The extensive research on the effects of these antioxidants on both aging and disease, indicates, that, like diseases, some aspects of aging can be prevented. Geza Hrazdina (Cornell): Using Genetic Engineering to Eliminate One Phytochemical at a Time and Test the Fruit for its Effects of Health Superoxide Dismutase An important part of the antioxidant defense system inside cells are the antioxidant enzymes. For example, superoxide dismutase converts superoxide into the less reactive chemicals (peroxide and oxygen). 2O2.- + 2H+ SOD H2O2 + O2 They Were Laughed At
In 1968, Joe McCord and Irwin Fridovich serendipitously discovered superoxide dismutase (SOD) as a contaminant of other enzymes. They suggested that it functioned in the body as a defense against endogenously generated superoxide. Although
they were laughed at, at the time, today, their discovery is recognized as the basis of a whole field of biology and medicine. Lou Gehrig's Disease The gene for superoxide dismutase
is defective in 20% of people with inherited amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig's disease. ALS results from the degeneration of motor neurons. Superoxide Dismutase in Commercial Products Some Contributors to Aging Genetic Influences: A defective superoxide dismutase enzyme speeds up the aging process by not being able to remove the super oxide free radical. Environmental Influences: Smoking speeds up the aging process by forming free radicals. Nutritional Influences: Too many sugars speed up the aging process by forming AGEs by the non-enzymatic Maillard reaction. Lots of antioxidants, including vitamins A, C and E slow down the aging process by scavenging free radicals. Green Cemeteries There are seven natural cemetery preserves in the United States. Greensprings Natural Cemetery Preserve on Irish Hill Road in Newfield is New York State's first natural cemetery. Embalming fluid is not used Caskets are biodegradable, made from local wood Good Luck on Prelim I There will be a review session in Call Aud Wednesday, February 21 at 9:05. I will sum up the first part of the semester during that session. ...
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- Spring '07
- The Digestive System, Senescence, reactive oxygen species, superoxide dismutase, Maillard reaction