Table 3.

Properties of arginine depriving enzymes

Arginine deiminase (E.C. 3.5.3.6)	Arginase (E.C.3.5.3.1)	Arginine decarboxylase (E.C.4.1.1.19)
Main products are citrulline and NH3	Main products are ornithine and urea	Main products are agmatine and CO2
At physiological pH, Mycoplasmal ADI is 300x more effective than arginase at depleting arginine	Very high alkaline pH optimum (pH 9.3) and has little enzymic activity at physiological pH	Mammalian ADC has a basic pH optimum (pH 8.23)
Circulatory half-life of ~ 4 h	Very short circulatory half-life (Approx. 30 min)	Not reported
Very high affinity for arginine (Km of 0.1–1 mM)	Low affinity for arginine (Km of 2–4 mM)	High affinity for arginine (Km of ~ 1 mM)
Most normal cells and tissues are able to take up citrulline from the circulation	Ornithine can only be reconverted back into arginine in the liver and can cause toxicity to extra-hepatic tissues by inhibiting protein synthesis	Agmatine is not converted back to arginine under normal physiological conditions, may lead to its accumulation and toxicity to normal cells
Only found in microorganisms and is strongly antigenic in mammals	Human enzyme, non-immunogenic	Found in plants, microbes and human brain
Tumor sensitivity to ADI is dependent on ASS expression	The sensitivity of tumors to rhArg is independent of ASS expression	Studied only in human cervical cancer (HeLa) cell lines
Efficacious only in ASS-negative tumors	Efficacious in both ASS-negative and OTC-negative tumors
No cofactor requirement	Mn2+ is essential for catalytic activity	Pyridoxal phosphate is a cofactor
Pegylation improves catalytic activity at physiological pH	Pegylation improves catalytic activity at physiological pH	PEGylation results in the total loss of catalytic activity

Abbreviations: ADT, arginine deprivation therapy; ADI, arginine deiminase; ASS, argininosuccinate synthetase; OTC, ornithine transcarbamoylase.