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J. Biol. Chem., Vol. 280, Issue 19, 16, May 13, 2005
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Classics
Isolation of the Coenzyme of the Galactose Phosphate-Glucose Phosphate Transformation (Caputto, R., Leloir, L. F., Cardini, C. E., and Paladini, A. C. (1950) J. Biol. Chem. 184, 333-350)
Uridine Diphosphate Acetylglucosamine (Cabib, E., Leloir, L. F., and Cardini, C. E. (1953) J. Biol. Chem. 203, 1055-1070)
Guanosine Diphosphate Mannose (Cabib, E., and Leloir, L. F. (1954) J. Biol. Chem. 206, 779-790)
Luis Federico Leloir (1906-1987) was born in Paris but moved to Buenos Aires with his Argentine parents when he was 2 years old. He attended the University of Buenos Aires and graduated with an M.D. in 1932. Leloir got a job at the University hospital but left the bedside for the bench 2 years later. As he recalled, "When I practiced medicine, except for surgery, digitalis, and a few other active remedies, we could do little for our patients. Antibiotics, psychoactive drugs, and all the new therapeutic agents were unknown. It was therefore not strange in 1932 that a young doctor such as I should try to join efforts with those who were trying to advance medical knowledge" (1).1
The most active research laboratory in town was run by Bernardo A. Houssay, who would later be awarded the Nobel Prize with Carl and Gerty Cori for their work on the role of the pituitary gland in carbohydrate metabolism. Leloir joined Houssay's laboratory as a graduate student and studied the role of the adrenals in carbohydrate metabolism.
After Leloir finished his thesis work, Houssay advised him to study abroad.
So, in 1936 Leloir moved to England to work at the Biochemical Laboratory of
Cambridge University. There, he collaborated with Malcolm Dixon on the effect
of cyanide and pyrophosphate on succinic acid dehydrogenase, Norman L. Edson
on ketogenesis using liver slices, and David E. Green on the purification and
properties of 
-hydroxybutyrate dehydrogenase.
Leloir returned to Buenos Aires after his time at Cambridge and started investigating the oxidation of fatty acids in the liver with J. M. Muñoz. They managed to produce an active cell-free system, which was an accomplishment since at that time it was thought that oxidation could only occur in intact cells. Leloir also worked with E. Braun Menéndez, Juan Carlos Fasciolo, and A. C. Taquini on the mechanism of renal hypertension and the formation of angiotensin.
In 1944, Leloir left Buenos Aires again. This time he went to Washington University in St. Louis to work with Carl and Gerty Cori, who were featured in a previous Journal of Biological Chemistry (JBC) Classic (2). While in the States, Leloir reunited with Green and spent some time at the College of Physicians and Surgeons at Columbia University working on the purification of aminotransferases.
After his stay in the United States, Leloir returned to the Institute of Physiology in Buenos Aires. He worked there for a time and then left for a private institution recently created, the Instituto de Investigaciones Bioquimicas Fundacion Campomar (now Fundacion Instituto Leloir), where he remained until his death. In collaboration with Ranwel Caputto, Carlos E. Cardini, Raúl Trucco, and Alejandro C. Paladini, Leloir started to work on the metabolism of galactose. The project was initiated when Caputto presented some preliminary results that indicated that mammary gland homogenates could produce lactose when incubated with glycogen. The group performed many experiments with mammary gland extracts but generally got ambiguous results, mainly due to their lack of a reliable method for lactose detection. Discouraged, they decided to focus on the breakdown of lactose by Saccharomyces fragilis, hoping that this would give them information on the mechanism of lactose synthesis.
Leloir and his colleagues isolated lactase from the yeast and determined that galactose was phosphorylated to produce galactose 1-phosphate. They synthesized glucose 1-phosphate and galactose 1-phosphate and observed that the esters were used when incubated with enzymes from galactose-adapted yeast. At first they thought that only one factor was required for this reaction, but soon realized that two factors were involved: one for the conversion of galactose 1-phosphate into glucose 1-phosphate and another for the formation of glucose 6-phosphate, as shown in the following reaction.
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Another result of the discovery of UDPG was the isolation and characterization of the sugar nucleotides UDP-N-acetylglucosamine (UDPAG) and guanosine diphosphate mannose (GDPM), which are the subjects of the remaining two JBC Classics reprinted here. UDPAG was originally detected as an impurity in UDPG concentrates and was called UDP-X until Leloir was able to identify the sugar moiety as N-acetylglucosamine. Similarly, GDPM was first detected by paper chromatography of UDPG preparations that were purified by anion exchange. UDPAG and GDPM are now known to be involved in the biosynthesis of numerous glycoconjugates.
Leloir's extensive work on sugar nucleotides and his contributions to biochemistry received the recognition they deserved when he was awarded the Nobel Prize in Chemistry in 1970, "for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates."
FOOTNOTES
1 All biographical information on Luis F. Leloir was taken from Refs.
1 and
8. We thank Armando J. Parodi,
Ph.D., of the Fundacion Instituto Leloir, for helpful comments in the
preparation of this JBC Classic Introduction. 
REFERENCES
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