SOME CATALYTIC ASPECTS OF DISEASE AND DRUGS 241 



(and this is very sensitive to reagents), alphaglutarate oxidase, malate 

 oxidase, succinoxidase, and the phosphorylases, myosin (adenosine tri- 

 phosphatase) and myokinase. 



"Not affected, and hence not SH enzymes, are: lactate oxidase, iso- 

 citrate oxidase, acid phosphatase, carbonic anhydrase, polyphenol oxi- 

 dase and catalase, although they may have SH groups in their protein. 

 SH enzymes of fat metabolism are: liver stearate oxidase, E. coli 

 stearate oxidase, betahydroxybutyric dehydrogenase, acetate oxidase, 

 pancreatic lipase; while among the enzymes concerned in protein 

 metabolism, SH enzymes include: d-amino acid oxidase, transaminase, 

 /-glutamic dehydrogenase and monamine oxidase, but not diamine 

 oxidase, pepsin or trypsin. 



"Barron and Singer concluded that the role of glutathione is to 

 produce reactivation of SH enzymes where they have been rendered 

 ineffective by oxidation or mercaptide formation. After all the years 

 of controversy about the role of glutathione, this is a rather interesting 

 postulate. 



"Thus we see that there is such a multiplicity of enzymes which the 

 arsenicals can attack, that we can scarcely put our finger on any one 

 point of attack where we could say: this will damage the parasite 

 before it will damage the host. One of the most sensitive enzymes was 

 pyruvate oxidase. Should we consider that arsenical attack upon this 

 enzyme is crucial for the parasites? 



"Reiner and Smythe 53 showed in 1934 that Trypanosoma equi- 

 perdum splits glucose to two moles of pyruvic acid. Perhaps the 

 amount of pyruvate oxidase which this parasite can form is limited, 

 for late in trypanosomiasis in the rat there is a pyruvic acid acidosis 

 in the host." 



In a note Dr. Leonard points out that this pyruvic acid formation 

 by Tr. equiperdum may account for its virulence in hosts, since 

 L. Reiner and co-workers found that Tr. Lewisi, which many common 

 gray rats may harbor in their blood as a low grade avirulent infection, 

 splits glucose to succinic acid (4 C chain) and acetic acid (2 C chain), 

 and both of these acids are readily handled by host tissues in processes 

 which do not require the aid of the limited essential dietary factor, 

 thiamine. 



Immunological experience shows that antigens closely alike 

 chemically may react with both their respective antibodies (cross 

 reactions). Similarly, enzymes may in some cases attack chemically 

 similar substrates (metabolites), and enzyme poisons or inhibitors 

 may be anticipated or fended off by chemically similar substances 

 which do not inhibit. The fact that para-aminobenzoic acid 

 (PABA) commonly nullifies the antibacterial activity of sulfa 



