Overriding a Block in Glycolysis
Michael P. was noticeably weak from his birth. He didn't move much, had poor muscle tone and difficulty breathing, and grew exhausted merely from the effort of feeding. At the age of two and a half months, he suffered his first seizure, staring and jerking his limbs for several frightening minutes. Despite medication, his seizures continued, occurring more frequently.
The doctors were puzzled because the results of most of Michael's many medical tests were normal — with one notable exception, His cerobrospinal fluid (the fluid that bathes the brain and spinal cord) was unusually low in glucose and lactic acid. These deficiencies told the physicians that Michael's cells were not performing glycolysis or anaerobic respiration.
Hypothesizing that a profound lack of ATP was causing the symptoms, medical researchers decided to intervene beyond the block in the boy's metabolic pathway, taking a detour to energy production. When Michael was seven and a half months old, he began a diet rich in certain fatty acids. Within four days, he appeared to be healthy for the very first time! The diet had resumed aerobic respiration at the point of acetyl coenzyme A formation by supplying an alternative to glucose. Other children with similar symptoms have since enjoyed spectacular recoveries similar to Michael's thanks to the dietary intervention, but doctors do not yet know the long-term effects of the therapy. This medical success story, however, illustrates the importance of the energy pathways—and how valuable our understanding of them can be. ■
lustrâtes how medical sleuths traced one boy's unusual combination of symptoms to a block in glycolysis.
For glycolysis to continue, NADH + H+ must be able to deliver its electrons to the electron transport chain, thus replenishing the cellular supply of NAD+. In the presence of oxygen, this is exactly what happens. Oxygen acts as the final electron acceptor at the end of the electron transport chain, enabling the chain to continue processing electrons and recycling NAD+.
Under anaerobic conditions, however, the electron transport chain has nowhere to unload its electrons, and it can no longer accept new electrons from NADH. As an alternative, NADH + H+ can give its electrons and hydrogens back to pyruvic acid in a reaction that forms lactic acid. Although this regenerates NAD+, the buildup of lactic acid eventually inhibits glycolysis, and ATP production declines. The lactic acid diffuses into the blood, and when oxygen levels return to normal, the liver converts the lactic acid back into pyruvic acid, which can finally enter the aerobic pathway.
If enough oxygen is available, the pyruvic acid generated by glycolysis can continue through the aerobic pathways (see fig. 4.6). These reactions include the synthesis of acetyl coenzyme A (as'e-til ko-en'zlm A) or acetyl CoA, the citric acid cycle, and the electron transport chain. In addition to carbon dioxide and water, the aerobic reactions themselves yield up to thirty-six ATP molecules per glucose.
Aerobic respiration (a-er-o'bik res"pi-ra'shun) is a sequence of reactions that begins with pyruvic acid produced by glycolysis moving from the cytosol into the mitochondrion (fig. 4.10). From each pyruvic acid, enzymes inside the mitochondria remove two hydrogen atoms, a carbon atom, and two oxygen atoms generating NADH and a CO2 and leaving a 2-carbon acetic acid. The acetic acid then combines with a molecule of coenzyme A (derived from the vitamin pantothenic acid) to form acetyl CoA. CoA "carries" the acetic acid into the citric acid cycle.
Lactic acid formation occurs in an interesting variety of circumstances. Coaches measure lactic acid levels in swimmers' and sprinters' blood to assess their physical condition. Lactic acid accumulates to triple the normal levels in the bloodstreams of children who vigorously cry when they are being prepared for surgery but not in children who are calm and not crying. This suggests that lactic acid formation accompanies stress.
CoA Coenzyme A P Phosphate • Carbon atom
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.