50 Years Ago in Biochemistry
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In the 1950s the field of oxidative phosphorylation was so nebulous and confused that all possible concepts, facilities, and tools were needed to advance knowledge of the subject. When Hotchkiss found that gramicidin blocked phosphate uptake by Staphylococci, we had postulated that this antibiotic uncoupled phosphorylation from oxidation -- a concept we had first proposed for the metabolic effect of 2,4,-dinitrophenol (DNP).[1,2] From then on, we collected antibiotics from many sources hoping that some would be useful inhibitors of cellular respiration and phosphorylation. The first of these found to be effective was usnic acid [3] which, in micromolar concentrations, uncoupled phosphorylation in washed liver particles. We also discovered that antimycin A blocked the respiratory system of bakers yeast and enhanced aerobic fermentation to the anaerobic rate. This information was passed on to Ahmad and Strong in the next laboratory, who were working intensively on antimycin.
By 1958 we had tested more than 60 antibiotics and had found about one of 10 to have interesting effects on mitochondrial metabolism and function. When we later confined our screening to antifungals that were non-toxic to anaerobic bacterial growth, one of every three or four new antibiotics was a "keeper."
The 1958 paper reported the inhibition of mitochondrial respiration by oligomycin and its reversal by DNP. It inhibited ATP hydrolysis induced by DNP, Ca2 + , deoxycholate, and triiodothyroacetic acid. We concluded that oligomycin acts on an enzyme involved in phosphate fixation or in phosphate transfer rather than on enzymes in electron transport. Regardless of which theory of oxidative phosphorylation an investigator espoused, he was soon finding oligomycin useful in his work. We kept no record of the number of requests we received for this antibiotic but I know we disposed of a gross of small vials before we began folding samples into glazed paper and sending them by letter mail.
Valacidin (identical with Pfizer's streptonigrin) was found to reverse respiratory inhibition by oligomycin or antimycin "indicating that it acts as an electron carrier from DPNH to cytochromes."
The paper also reported for the first time the effects of nigericin and dianemycin on mitochondrial respiration, phosphorylation, and ATP hydrolysis.
Dianemycin was named for Diane Johnson, the second author of the paper. She is a "classic" in her own right. After 10 years as my technician Johnson decided to take a doctorate in history of science. Although her undergraduate academic record was brilliant, as a Ph.D. candidate she suffered the disgrace of her only B grade -- in a one-credit seminar. (The professor who awarded it has since left this University and I have wondered whether he was encouraged to do so by the assistant dean of his college -- Diane Johnson.) She is also chairman of the Drug Quality Council for the State of Wisconsin -- their task, to determine whether generic drug products are equivalent to brand name products. Believe it or not, she has just been appointed assistant director of athletics at the University of Wisconsin!
Bill McMurray was a postdoctorate fellow from the University of Western Ontario, where he is now professor of biochemistry and where he later discovered the effects of valinomycin on mitochondria.
I have always considered this one of the trivial papers from our laboratory but am pleased that others have found it useful enough to cite it. - Henry A. Lardy, Institute for Enzyme Research, University of Wisconsin, April 12, 1978
Reference:
H.A. Lardy, D. Johnson, W.C. McMurray, Antibiotics as tools for metabolic studies.I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems. Arch. Biochem. Biophys. 78:587-97, 1958
References in essay:
1. Lardy H A and Elvehjem C A. Biological oxidations and reductions. Ann. Rev. Biochem. 14:1- 30, 1945.
2. Lardy H A and Phillips P H. The effect of thyroxine and dinitrophenol on sperm metabolism. J. Biol. Chem. 149:177-82, 1943.
3. Johnson R B, Feldott G & Lardy H A. The mode of action of the antibiotic, usnic acid. Arch. Biochem. 28:317-23, 1950. http://www.the-scientist.com
Educational Impact on Detection of Alzheimer’s
People who spend fewer years in school may be slower to realize that they are suffering from the early symptoms of Alzheimer’s disease than those who are more highly educated, a new report found. The lag may explain why, overall, less educated people tend to be diagnosed with Alzheimer’s at a slightly later age than those who are highly educated. At the same time, problems with memory and thinking may have advanced further by the time those with little schooling are diagnosed with the disease.
The findings, published in the Archives of Neurology, come from scientists at the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis. The researchers reviewed data on nearly 1,500 Alzheimer's patients from their center. They also reviewed files on more than 21,000 patients from the National Alzheimer's Coordinating Center, a collaboration of approximately 30 Alzheimer's disease research centers nationwide.
"We may have a group of people who are at risk for slightly delayed detection of Alzheimer's disease," said lead author Catherine Roe, Ph.D., a neurology research instructor at Washington University. "Early detection of Alzheimer's disease is important as we progress toward treatments and cures because those treatments will need to be applied as early as possible to have the maximum possible benefit."
The new study revealed that patients with 12 years or more of schooling were on average slightly younger when diagnosed with Alzheimer's disease than patients with less than eight years of schooling. Age of diagnosis for a group with eight to 11 years of schooling fell in-between the other two groups. The researchers also analyzed the severity of patients' dementia when they went to the Alzheimer's disease center for the first time. They found that patients with fewer years of education were likely to be more severely impaired on their first visit.
Fewer years of formal schooling have been linked to an increased risk for Alzheimer’s in earlier studies. Higher levels of education, on the other hand, may be protective. One theory is that education helps build a strong network of interconnections between nerve cells in the brain. This network may act as a so-called “brain reserve,” allowing the brain to function normally as cells die from Alzheimer’s. Why would someone with more schooling, then, be diagnosed with Alzheimer’s sooner? The researchers propose that those with lower education levels may be slower to notice the early signs of disease, only going to see a specialist after their symptoms become impossible to ignore. Those with more education, on the other hand, may become aware of their symptoms while they are still relatively subtle and seek a specialists' help early on in the disease process.
"People with higher education levels may be more likely to have a job or a hobby that makes early cognitive impairment more obvious, as well as better access to medical care," Dr. Roe said. "These could be factors that we need to incorporate into our procedures for screening patients for early signs of cognitive impairment." http://www.medicalnewstoday.com
By 1958 we had tested more than 60 antibiotics and had found about one of 10 to have interesting effects on mitochondrial metabolism and function. When we later confined our screening to antifungals that were non-toxic to anaerobic bacterial growth, one of every three or four new antibiotics was a "keeper."
The 1958 paper reported the inhibition of mitochondrial respiration by oligomycin and its reversal by DNP. It inhibited ATP hydrolysis induced by DNP, Ca2 + , deoxycholate, and triiodothyroacetic acid. We concluded that oligomycin acts on an enzyme involved in phosphate fixation or in phosphate transfer rather than on enzymes in electron transport. Regardless of which theory of oxidative phosphorylation an investigator espoused, he was soon finding oligomycin useful in his work. We kept no record of the number of requests we received for this antibiotic but I know we disposed of a gross of small vials before we began folding samples into glazed paper and sending them by letter mail.
Valacidin (identical with Pfizer's streptonigrin) was found to reverse respiratory inhibition by oligomycin or antimycin "indicating that it acts as an electron carrier from DPNH to cytochromes."
The paper also reported for the first time the effects of nigericin and dianemycin on mitochondrial respiration, phosphorylation, and ATP hydrolysis.
Dianemycin was named for Diane Johnson, the second author of the paper. She is a "classic" in her own right. After 10 years as my technician Johnson decided to take a doctorate in history of science. Although her undergraduate academic record was brilliant, as a Ph.D. candidate she suffered the disgrace of her only B grade -- in a one-credit seminar. (The professor who awarded it has since left this University and I have wondered whether he was encouraged to do so by the assistant dean of his college -- Diane Johnson.) She is also chairman of the Drug Quality Council for the State of Wisconsin -- their task, to determine whether generic drug products are equivalent to brand name products. Believe it or not, she has just been appointed assistant director of athletics at the University of Wisconsin!
Bill McMurray was a postdoctorate fellow from the University of Western Ontario, where he is now professor of biochemistry and where he later discovered the effects of valinomycin on mitochondria.
I have always considered this one of the trivial papers from our laboratory but am pleased that others have found it useful enough to cite it. - Henry A. Lardy, Institute for Enzyme Research, University of Wisconsin, April 12, 1978
Reference:
H.A. Lardy, D. Johnson, W.C. McMurray, Antibiotics as tools for metabolic studies.I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems. Arch. Biochem. Biophys. 78:587-97, 1958
References in essay:
1. Lardy H A and Elvehjem C A. Biological oxidations and reductions. Ann. Rev. Biochem. 14:1- 30, 1945.
2. Lardy H A and Phillips P H. The effect of thyroxine and dinitrophenol on sperm metabolism. J. Biol. Chem. 149:177-82, 1943.
3. Johnson R B, Feldott G & Lardy H A. The mode of action of the antibiotic, usnic acid. Arch. Biochem. 28:317-23, 1950. http://www.the-scientist.com
Educational Impact on Detection of Alzheimer’s
People who spend fewer years in school may be slower to realize that they are suffering from the early symptoms of Alzheimer’s disease than those who are more highly educated, a new report found. The lag may explain why, overall, less educated people tend to be diagnosed with Alzheimer’s at a slightly later age than those who are highly educated. At the same time, problems with memory and thinking may have advanced further by the time those with little schooling are diagnosed with the disease.
The findings, published in the Archives of Neurology, come from scientists at the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis. The researchers reviewed data on nearly 1,500 Alzheimer's patients from their center. They also reviewed files on more than 21,000 patients from the National Alzheimer's Coordinating Center, a collaboration of approximately 30 Alzheimer's disease research centers nationwide.
"We may have a group of people who are at risk for slightly delayed detection of Alzheimer's disease," said lead author Catherine Roe, Ph.D., a neurology research instructor at Washington University. "Early detection of Alzheimer's disease is important as we progress toward treatments and cures because those treatments will need to be applied as early as possible to have the maximum possible benefit."
The new study revealed that patients with 12 years or more of schooling were on average slightly younger when diagnosed with Alzheimer's disease than patients with less than eight years of schooling. Age of diagnosis for a group with eight to 11 years of schooling fell in-between the other two groups. The researchers also analyzed the severity of patients' dementia when they went to the Alzheimer's disease center for the first time. They found that patients with fewer years of education were likely to be more severely impaired on their first visit.
Fewer years of formal schooling have been linked to an increased risk for Alzheimer’s in earlier studies. Higher levels of education, on the other hand, may be protective. One theory is that education helps build a strong network of interconnections between nerve cells in the brain. This network may act as a so-called “brain reserve,” allowing the brain to function normally as cells die from Alzheimer’s. Why would someone with more schooling, then, be diagnosed with Alzheimer’s sooner? The researchers propose that those with lower education levels may be slower to notice the early signs of disease, only going to see a specialist after their symptoms become impossible to ignore. Those with more education, on the other hand, may become aware of their symptoms while they are still relatively subtle and seek a specialists' help early on in the disease process.
"People with higher education levels may be more likely to have a job or a hobby that makes early cognitive impairment more obvious, as well as better access to medical care," Dr. Roe said. "These could be factors that we need to incorporate into our procedures for screening patients for early signs of cognitive impairment." http://www.medicalnewstoday.com
Enzymes designed to improve berry juice use
A new range of enzymes are designed to improve the juice volume and vitamin yield of blackcurrants for beverage use, in order to maximise the benefits of the superfruits, their manufacturer says. http://www.nutraingredients.com
A new range of enzymes are designed to improve the juice volume and vitamin yield of blackcurrants for beverage use, in order to maximise the benefits of the superfruits, their manufacturer says. http://www.nutraingredients.com
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