Enzyme creatine kinase

An example of a random, single-displacement mechanism is seen in the enzyme creatine kinase, a phosphoryl-transfer enzyme that uses ATP as a phosphoryl... 

In our laboratory, we have focused our attention on the syntheses of various analogs of creatine, 17, a substrate for the enzyme creatine kinase from rabbit muscle (2). The reaction catalyzed by this enzyme is... 

Use of the plasma enzyme creatine kinase Mb (CK-MB) in the diagnosis of myocardial infarction. 

The enzyme creatine kinase (CK) facilitates the transfer of phosphate and energy to a molecule of ADP to form ATP. Stores of creatine phosphate are sufficient to sustain approximately 15 more seconds of muscle contraction. Because this is a single-step process, it provides ATP very rapidly and is the first pathway for formation of ATP to be accessed. 

In addition to actin and myosin, other proteins are found in the two sets of filaments. Tropomyosin and a complex of three subunits collectively called troponin are present in the thin filaments and play an important role in the regulation of muscle contraction. Although the proteins constituting the M and the Z bands have not been fully characterized, they include a-actinin and desmin as well as the enzyme creatine kinase, together with other proteins. A continuous elastic network of proteins, such as connectin, surround the actin and myosin filaments, providing muscle with a parallel passive elastic element. Actin forms the backbone of the thin filaments [4]. The thin... 

The enzyme creatine kinase is present in two positions in the muscle fibre within the intermembrane space of the mitochondria and close to the myofibrils. 

The enzyme creatine kinase (CK) is formed of two subunits that can either be of the brain (B) type or the muscle (M) type, and different combinations of these types lead to isozymes that predominate in the brain (BB), skeletal muscle (MM), and heart muscle (MB). 

Phosphocreatine (Fig. 13-5), also called creatine phosphate, serves as a ready source of phosphoryl groups for the quick synthesis of ATP from ADP. The phosphocreatine (PCr) concentration in skeletal muscle is approximately 30 nra, nearly ten times the concentration of ATP, and in other tissues such as smooth muscle, brain, and kidney [PCr] is 5 to 10 mM. The enzyme creatine kinase catalyzes the reversible reaction... 

Figure I. Composite diagram summarizing the roles of histidine imidazole groups at the active sites of the phosphotransferase enzymes creatine kinase (CrK), pyruvate kinase (PK), and adenylate...

In the hospital, ECG and laboratory tests are performed promptly to determine the subsequent treatment strategy. When car-diomyocytes die, contractile proteins (troponin) or myocardial enzymes (creatine kinase, CK-MB) are liberated and can be detected in blood for diagnostic purposes. Marked elevation of the ST segment in the ECG raises the strong suspicion of a complete occlusion of a coronary artery (ST elevation MI, STEMI). In these MI patients, reperfusion of the affected area as early and as completely as Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Enzymes have been classified by an international Enzyme Commission (EC) and assigned EC numbers. Thus the enzyme creatine kinase (the muscle enzyme that catalyses the energy storage reaction ATP + creatine —> ADP + phosphocreatine) has the EC number 2.7.3.2, these numbers successively referring to a transferase function (2), a phosphotransferase function (7), phosphotransfer with a nitrogen (N) acceptor (3) and creatine kinase per se (2). 

To illustrate how this system is used to name an enzyme, consider the enzyme creatine kinase that catalyzes the reaction ... 

Blood enzymes following myocardial infarction. The activities of two enzymes, creatine kinase (CPK) and lactate dehydrogenase (LDH) were measured in the blood plasma of a patient at various times following a myocardial infarction. 

Phosphoryl group transfer from creatine phosphate to ADP is catalyzed by the enzyme creatine kinase. 

As its high phosphate transfer potential suggests (see Figure 3.7), this compound is capable of phosphorylating ADP very efficiently. The reaction is catalyzed by the enzyme creatine kinase as follows ... 

Proteins that differ somewhat in primary structure and properties from tissue to tissue, but retain essentially the same function, are called tissue-specific isoforms or isozymes. The enzyme creatine kinase is an example of a protein that exists as tissue-specific isozymes, each composed of two subunits with 60 to 72% sequence homology. Of the two creatine kinases that bind to the muscle sarcomere, the M form is produced in skeletal muscle, and the B polypeptide chains are produced in the brain. The protein comprises two subunits, and skeletal muscle therefore produces an MM creatine kinase, and the brain produces a BB form. The heart produces both types of chains and therefore forms a heterodimer, MB, as well as an MM dimer. Two more creatine kinase isozymes are found in mitochondria, a heart mitochondrial creatine kinase, and the universal isoform found in other tissues. (In general, most proteins present in both the mitochondria and cytosol will be present as different isoforms.) The advantage conferred on different tissues by having their own isoform of creatine kinase is unknown. However, tissue-specific isozymes such as MB creatine kinase are useful in diagnosing sites of tissue injury and cell death. 

A somewhat similar picture has been obtained by electron-spin resonance studies of two manganese-containing enzymes creatine kinase and muscle enolase. In the former, manganese was shown to form a bond to the coenzyme (adenosine diphosphate) and to the substrate, but not to the protein in the latter, manganese seemed to act as a bridge between substrate and protein (Cohn and Leigh, 1962). 

Liver A survey of abnormal liver function (raised alanine aminotransferase) or raised muscle enzyme creatine kinase (CK) activity in a large ambulatory population showed that values over three times the upper limit of the reference range were deemed to be rare and differed little from the incidence of enzyme rises that have been reported for placebo [8 ]. 

From a collection of enzymes, and the appropriate substrates, systems could be devised to arrange for the analysis of e.g., adenosine triphosphate or even the enzyme creatine kinase (Green et al., 1984) (Figure 12). Indeed, there would appear to be no limit to the complexity of such arrangements. 

---