Isoenzyme
As isoenzymes , including isozymes , refers to various forms of enzymes , if they have the same chemical reaction catalyzed . The individual forms have the same specificity for the converted substrate , but differ in their structure, in the case of proteins in the amino acid sequence .
Isoenzymes are functionally corresponding enzymes that perform similar or identical tasks in different individuals, in different organs of an individual, in different organelles of a cell or in the same cell compartment . Their often minor structural differences are genetically determined and lie in the primary structure , in the case of oligomeric isoenzymes in the composition of their subunits.
Isoenzymes often differ in their isoelectric points and can be separated electrophoretically . Using the methods of enzyme kinetics , their catalytic properties are examined in more detail and characterized according to optimum pH and temperature. Because different enzymes for the same reaction can have different kinetic parameters ( affinity , turnover number ) under the same conditions and develop their optimal activity under different cellular conditions. In addition, isoenzymes can respond differently to regulatory signals ( inhibitors , activators ). In an organism, therefore, different distribution patterns of isoenzymes can usually be seen depending on its development phase.
The presence of isoenzymes thus indicates
- a finer control of metabolic reactions,
- different metabolic patterns in different organs,
- different localization and role of an enzyme in the metabolism within a cell type.
Examples
It is not uncommon for a species to have multiple variants of a gene that codes for a specific enzyme . If different alleles are present at the same gene location in different individuals , their gene products are different; such isoenzymes are also called allelozyme . In humans, for example, are for the enzyme
- Glucose-6-phosphate dehydrogenase (G6PD) over sixty natural variants known, which can be traced back to genetic variation at the same gene locus (on chromosome X), in which a protein is formed as a result of a single nucleotide exchange in the coding base sequence of the DNA, its sequence of over five hundred amino acids is changed in only one position of the amino acid sequence. Compared to the most common form (variant B), however, most of these enzyme variants show a more or less limited catalytic activity, so that there is a lack of fully functional G6PD ( glucose-6-phosphate dehydrogenase deficiency ), which may be a clinical picture can express ( favism ). This ( X-linked recessive hereditary ) predisposition is considered to be the most common enzymopathy worldwide .
A distinction is to be made between different forms of an enzyme that can be formed in an individual from the same DNA segment of a certain gene locus by rewriting different areas in mRNA during transcription or by omitting them through alternative splicing of exons .
- For G6PD, for example, several isoforms with alternative sequences of different lengths are known in which different exons are expressed (isoform short [515 AA ], isoform 3 [545 AA], isoform long [561 AA]). These protein isoforms of the same gene variant represent isoenzymes in the same individual and occur tissue-specifically, the long isoform being found here in lymphoblasts , granulocytes and sperm.
In addition isoenzymes may occur when an enzyme in its quaternary structure composed of multiple protein subunits, such as a heterodimeric , or - tetrameric is. This often occurs when genes at two or more gene loci have arisen through previous gene duplication , which after mutations now code for slightly different proteins which can associate to form a complex.
- Lactate dehydrogenases (LDH) occur as tetramers, the four subunits of which can be the same (homotetramer) or not (heterotetramer). The distribution pattern of these oligomeric isoenzymes is different in the tissues of the human organism. In the heart muscle there is predominantly an LDH (LDH-1: H 4 ) made up of the same subunits of type H , in skeletal muscle mainly one of type M (LDH-5: M 4 ), also in the liver. In addition to heterotetrameric LDH from such subunits (LDH-2: H 3 M 1 ; LDH-3: H 2 M 2 ; LDH-4: H 1 M 3 ), LDH with other types of subunits is now also known.
- As a dimer, creatine kinases (CK) consist of two subunits. CK-MM occur specifically in skeletal muscle , CK-BB in the brain and CK-MB in the heart muscle . An increased level of the isoenzyme -MB in the blood indicates a heart attack .
Isoenzymes can also be present in eukaryotic cells as genetically independent products of genes that do not belong to the same genome . Because in addition to the nuclear genome in the cell nucleus , an additional genome can be present in some organelles , a chondrioma in a mitochondrion and a plastome in plastids .
- For creatine kinase, for example, one can also find the isoenzyme CK-MiMi from mitochondria.
- Also, malate dehydrogenase (MDH) in the cytosol is different from the one in the mitochondrion, a Glyoxisom or chloroplast ; these are also isoenzymes.
In a broad sense, depending on the totality considered for a comparison, the different forms of functionally similar enzymes in organisms of different species or kingdoms are also referred to as isoenzymes ,
- for example the glucokinases of vertebrates , or the hexokinases of living things.
Individual evidence
- ↑ a b see entry G6PD_HUMAN in the database for proteins UniProt .