Isoenzyme tissue-specific patterns

One can still go to a step further and carry out comparative analyses of the first secondary gene products, the polypeptides or proteins. Consequent on the introduction of a suitable method, namely, zone electrophoresis on different supports, phase- and tissue-specific protein patterns have been detected in a wealth of experiments in recent years. As an example tissue-specific patterns of soluble proteins from different parts of the tulip are shown (Fig. 147). Enzymes, of course, also number among the proteins. We have already dealt with isoenzymes, multiple... 

LDH [molecular weight (MW) about 150,000] occurs in most tissues and consists of isoenzymes whose electrophoretic pattern is tissue specific. There are... 

The tissue specificity of isoenzyme patterns of LDH is useful in clinical medicine. Such pathological conditions as myocardial infarction, infectious hepatitis, and muscle diseases involve cell death of affected tissue, with release of cell contents to the blood. The pattern of LDH isoenzymes in the blood serum is representative of the tissue that released the isoenzymes. This information can be used to diagnose such conditions and to monitor the progress of treatment. 

Distinct tissue specificity of isoenzyme patterns is frequently observed. Also, different organelles within a single cell type may each contain different populations of isoenzymes. The question arises whether such specific expressions of isoen mae patterns within a tissue or cell are of physiological importance in meeting special metabolic needs of a certain state of differentiation. The fact that one observes a transition of a relatively great number of isoenzyme patterns during development seems to point to an adaptation to the states of differentiation. The appearance of a new, stably maintained, isoenzyme pattern within a cell population represents a step in differentiation. 

At the time LDH isoenzymes were first detected, it was also foimd that every organ or tissue showed a characteristic tissue-specific isoenzyme pattern. Much attention was paid to LDH, which at the time... 

Tissue-specific isoenzyme patterns have also been reported for CPK (Burger et al., 1964 Eppenberger et al., 1964). There is a tendency... 

Besides different isoenzyme patterns in various tissues and organs, specific patterns can also be found in different organelles of a cell. Frequently, we can see one type of isoenzyme or isoenzyme pattern in the soluble part of a cell and another type associated with an organelle of the same cell. 

Fig. 148. Tissue-specific isoenzyme pattern of the peroxidase of the petunia (Petunia hybrida). (A) flower buds, (B) young leaves, (C) old leaves, (D) young shoots, (E) old shoots, (F) root, (from Hess 1967).

Multiple gene loci and their resultant isoenzymes provide a means for the adaptation of metabolic patterns to the changing needs of different organs and tissues in the course of normal development or in response to environmental change. Pathological conditions may also be associated with alterations in the activities of specific isoenzymes. 

Between meals, a decreased insulin level and increased levels of insulin counter-regulatory hormones (e.g., glucagon) activate hpolysis, and free fatty acids are transported to tissues bound to serum albumin. Within tissnes, energy is derived from oxidation of fatty acids to acetyl CoA in the pathway of -oxidation. Most of the enzymes involved in fatty acid oxidation are present as 2-3 isoenzymes, which have different but overlapping specificities for the chain length of the fatty acid. Metabolism of unsaturated fatty acids, odd-chain-length fatty acids, and medium-chain-length fatty acids requires variations of this basic pattern. The acetyl CoA produced from fatty acid oxidation is principally oxidized in the TCA cycle or converted to ketone bodies in the liver. 

To explain the CPK isoenzyme pattern in hereditary muscular dystrophy Schapira et al. (1968) and Cao et al. (1971) suggested that the organism simply fails to convert the fetal to the adult CPK pattern. Hooton and Watts (1966), however, claimed that hereditarily dystrophic mice contained an MM-CPK composed of two nonidentical subunits M and M. Fingerprints of the M polypeptide chain appeared to differ from those of the M subunit by a single peptide. Since the MM dimer showed only half the activity of the normal enzyme it was assumed that the M subunit was inactive. This would also explain why no M M enzyme was detected. Studies of CPK in dystrophic chickens and dystrophic humans could not confirm the existence of a distinct isoenzyme in dystrophic tissues (Roy et al, 1970). Should it exist, moreover, the question would remain whether this alteration is a specific feature of muscular dystrophy or whether it is the mere consequence of increased proteolysis in damaged muscle. 

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