Human ‘creatine kinase conversion factor’ identified as a carboxypeptidase

Abstract

The effect of partially purified 'creatine kinase conversion factor' on rabbit muscle creatine kinase is shown to be that of a carboxypeptidase, removing the C-terminal lysine residue from both subunits. These changes fully explain the three-banded electrophoretic patterns of the partially and the fully modified rabbit and human enzymes. The factor also produces a similar electrophoretic pattern with haemoglobin A; comparison with the effects of carboxypeptidases A and B permits the inference that the C-terminal residues of both alpha- and beta-subunits are removed. Small synthetic peptides are poor or non-substrates. A low activity with hippuryl-L-lysine may be due to contamination of the preparation with carboxypeptidase N. The possibility has been excluded that the action of conversion factor on creatine kinase involves modification of the protein thiol groups. Mr, substrate-specificity, pH-activity profile and the effects of metal ions distinguish creatine kinase conversion factor from carboxypeptidases A, B and N. On the basis of this evidence it is proposed to give the conversion factor the provisional name of carboxypeptidase K.

Creatine Kinase and the Diagnosis of Myocardial Infarction

“…There are a number of reasons for considering that Sub-isoenzyres of CK In serum, but not in tissue extracts, CK-MM can be shown to exist as 3 subbands (CK-MM 1, CK-MM2, and CK-MM3). It now seems likely these are due to the conversion of the serum CK-M subunit to a form with greater anodal electrophoretic mobility by the action of a carboxypeptidase in serum; this enzyme splits off the positively charged C-terminal lysine to give a more negatively charged molecule [13,14]. In a similar fashion, CK-MB has two sub-bands.…”

Indices for the age of the creatine kinase M-chain in the blood

“…The ageing of the enzyme can be attributed to a modification in the M-chain caused by a serum protein [1,2], for which the name CK conversion factor has been proposed [3]. As the same protein modifies the alpha chain of enolase as well [7], the name modifying protein was introduced by Wevers et al [7], Recently, the modifying protein has been shown to have carboxypeptidase activity [8,9]. It separates the C-terminal lysine of the CK-M chain from the rest of the chain.…”

Purification and determination of the modifying protein responsible for the post-synthetic modification of creatine kinase (EC 2.7.3.2) and enolase(EC 4.2.1.11)

“…Recently, it has been claimed that this protein is a serum carboxypeptidase [4,5]. This paper describes the purification of this modifying protein from human serum and some of its characteristics.…”