Endogenous protein

One last class of mononuclear non-haem iron enzyme that we have not yet considered, consists of the microbial superoxide dismutases with Fe(III) at their active site. The crystal structure of the E. coli enzyme shows a coordination geometry reminiscent of protocatechuate 3,4-dioxygenase, with four endogenous protein ligands, three His and one Asp residue, and one bound water molecule (Carlioz et ah, 1988). 

The effects of antioxidants on protein oxidation were also studied in animal experiments. Barja et al. [73] demonstrated that feeding guinea pigs with vitamin C decreased endogenous protein oxidative damage in the liver. Administration of the mixture of antioxidants containing Trolox C, ascorbic palmitate, acetylcysteine, (3-carotene, ubiquinones 9 and 10, and (+)-catechin in addition to vitamin E and selenium to rats inhibited heme protein oxidation of kidney homogenates more efficiently than vitamin E + selenium [74]. 

Survivors may suffer a metabolic relapse at any time. The most common cause of relapse is intercurrent infection, which favors endogenous protein catabolism. As a consequence, the patient s limited capacity to oxidize BCAAs is overwhelmed and these compounds, together with their cognate ketoacids, accumulate to a toxic level. Relapse also can occur in association with surgery, trauma and emotional upset. 

Irreversible inhibition of CYPs is particularly worrisome as its consequences cannot be predicted easily or quantified from in vitro data the in vivo effect of an irreversible inhibitor is usually greater than that predicted based on affinity alone. Moreover, irreversible inhibition is generally the consequence of the production of reactive metabolites (electrophiles), which can also bind covalently to endogenous proteins and, in rare cases, trigger serious autoimmune reactions [4]. 

It has been noted [13, 33] that in several early publications describing total screening of biological extracts for peptide material insufficient care has been taken to avoid the ex vivo (or post mortem) formation of peptides in the extract where all proteases of the initial sample are released from the cellular compartments and are free to contact with the endogenous protein and peptide components. The resultant products with sometimes quite interesting activities should be formally considered... 

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