Born in Paris, Leloir was educated at Buenos Aires University, obtaining his MD there in 1932. He spent a year in Cambridge, England, studying under Gowland Hopkins, returning to Argentina to work at the Institute of Physiology until 1944, when – in conflict with the president, Juan Peron – he went into exile in America. In 1945 Leloir returned to Argentina, where he worked at the Institute of Biology and Experimental Medicine, set up in Buenos Aires by Bernard Hussey with private funding.

Despite working well away from the main biochemical research centers and using equipment that would have been thrown out of more fashionable laboratories, Leloir and his colleagues managed to surprise the biochemical world and make one of the major discoveries of the postwar years. In the 1930s Carl and Gerty Cori had demonstrated a process by which glycogen is synthesized and broken down. It was assumed that because there were enzymes capable, in vitro, of both breaking down glycogen into lactic acid and reversing the whole process, that this is what actually happened in the body.

It was therefore a matter of some surprise when Leloir and his colleagues announced in 1957 an alternative mechanism for the synthesis of glycogen. They discovered a new coenzyme, uridine triphosphate (UTP), analogous to adenosine triphosphate (ATP), which combined with glucose-1-phosphate to form a new sugar nucleotide, uridinediphosphate glucose (UDPG). In the presence of a specific enzyme and a primer UDPG will yield uridine diphosphate (UDP) and transfer the glucose to the growing glycogen chain. In the presence of ATP, UDP is converted back into UTP and the reaction can continue.

It was soon made clear that this is the actual process of glycogen synthesis taking place in the body; the Cori process is, in contrast, mainly concerned with the degradation of glycogen. It was for this work that Leloir was awarded the 1970 Nobel Prize for chemistry, the first Argentinian to be thus honored.