Homocysteine lactone

A similar editing process prevents isoleucyl-, leucyl-, and methionyl-tRNA synthetases from attaching L-homocysteine to tRNAs 260-263 In this case, instead of hydrolysis the editing site catalyzes conversion of the homocysteinyl-adenylate into homocysteine lactone. Naturally occurring mutations in tRNA molecules can sometimes have serious consequences. For example, a human mutation is responsible for a fragile mitochondrial isoleucine tRNA and serious cardiomyopathy and opthalmophegia (see also Box 18-B).263a... 

Homocysteine lactonizes readily in acidic solutions, and a study of the aqueous radiation chemistry of this thiolactone was undertaken to see how bonding of the sulphur to a carbonyl carbon modifies its reactivity to the aquated electron . (The normal H atom abstraction from sulphur by OH cannot occur.) The dissodative electron capture reaction which gives H S in the case of free thiols can be formulated ... 

Of considerable biochemical interest, several factors are associated with Alzheimer s disease but their significance is not known. An elevated plasma level of homocysteine is associated with the disease and it is considered as a risk factor for development of the disease. The damage may be caused by a degradation product of homocysteine a thio-lactone which causes oxidative damage to cells (Chapter 22 see Figure 22.7). 

The presence of homoserine, homoserine lactone, and acid hydrolysis of ribonuclease, 50 % inactivated by iodoacetate at pH 2.8, and the poor recovery of methionine provides another example for this type of breakdown of methionine sul-fonium salts (Gundlach et al, 1959b). The same products in varying proportions were observed in the decomposition of methionine carboxymethyl-... 

Methionine carboxymethylsulfonium salts These derivatives of methionine (isomers) are prepared by treating proteins with iodoacetic acid the reaction is most specific for methionine at acid pH ( 3.5). These derivatives are not affected by performic acid oxidation (see under methionine sulfoxide), but are degraded by acid hydrolysis to give methionine, carboxymethyl-homocysteine, homoserine and homoserine lactone (Gundlach et al. 1959). 

The derivatives of methionine formed by haloketones are not stable to the usual conditions of acid hydrolysis. These sulfonium salts are degraded in three different ways. Some methionine is regenerated, some homoserine and homoserine lactone is formed and possibly the homocysteine derivative of the general structure indicated below is produced where X represents the rest of the affinity label. 

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