Gene/Protein Disease Symptom Drug Enzyme Compound
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Copper toxicity occurred in North Ronaldsay sheep fed on a diet of terrestrial herbage relatively high in molybdenum. Five sheep were taken from the island of North Ronaldsay, Orkney to the veterinary investigation centre at Thurso and fed solely on the herbage of the laboratory paddocks, supplemented in winter by hay made from these paddocks. The level of copper, molybdenum, zinc and total sulphur in the terrestrial herbage was analysed, together with the seaweeds which form the major part of the diet on North Ronaldsay. Serum copper, vitamin B12 and serum aspartate aminotransferase levels were obtained. Four of the five sheep died on this diet of terrestrial herbage and had liver copper levels of 1379, 1723, 2279 and 2281 mg/kg. The susceptibility of the North Ronaldsay breed of Orkney sheep to copper poisoning when first introduced to a diet of purely terrestrial herbage is demonstrated by the high liver copper levels of the four dead sheep compared to the normal serum copper levels and unimpaired health of two other breeds of sheep and a north country Cheviot cross North Ronaldsay ram.
Vet Rec 1982 Sep 25
PMID:Copper poisoning in sheep from North Ronaldsay maintained on a diet of terrestrial herbage. 714 42

Research on the mechanism of action of coenzyme B12, adenosylcobalamin, as a graduate student introduced the author to the field of organic free radicals in enzymology. Twenty years later, related work on S-adenosylmethionine (SAM) as a "poor man's coenzyme B12" was initiated in a detailed analysis of the mechanism of action of lysine 2,3-aminomutase (LAM). The interconversion of L-lysine and L-beta-lysine is catalyzed by LAM, which requires SAM, pyridoxal-5'-phosphate (PLP), and a [4Fe-4S] cluster as coenzymes. The mechanism of this reaction has been delineated as a radical isomerization, in which radical formation is initiated by the [4Fe-4S]-dependent cleavage of the SAM into methionine and the 5'-deoxyadenosyl radical. The mechanism of this process is discussed, together with the role of this radical in hydrogen abstraction from lysine to initiate the substrate radical isomerization. The chemistry underlying the functions of SAM, PLP, and [4Fe-4S] in the action of LAM is novel in all respects, except for the formation of a lysine-PLP aldimine at the active site. Of the four free radicals in the mechanism, three have been characterized by EPR spectroscopy. In the suicide inactivation of adenosylcobalamin-dependent dioldehydrase (DDH) by glycolaldehyde, the formation of cob(II)alamin and 5'-deoxyadenosine is accompanied by the conversion of glycolaldehyde to cis-ethanesemidione radical at the active site. The cis-ethanesemidione radical has been characterized by EPR spectroscopy. Its exceptional stability at the active site is the basis for the inactivation of DDH by glycolaldehyde.
Chem Rec 2001
PMID:The role of radicals in enzymatic processes. 1189 68

The chronology of the discoveries along the pathway of vitamin B12 biosynthesis is reviewed from a personal perspective, including discussion of the most recent finding that two pathways to B12 exist--one aerobic and one anaerobic--which differ mainly in the ring contraction mechanisms which convert porphyrin to corrin.
Chem Rec 2001
PMID:Reflections on the discovery of nature's pathways to vitamin B12. 1189 20


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