alkaline phosphatase isoenzymes?

 

Isoenzymes

It was a tremendous step forward for research on the biochemistry of differentiation when it was discovered that some of the universally distributed enzymes have different molecular forms with a variety of subunits, characteristic of different tissues. Market and Møller (1959) were the first to make a survey of the patterns of nonspecific esterases in developing tissues of vertebrates and to recognize tissue-specific differences both in the activities of the different enzymes and in their polypeptide subunits.

A general survey of isoenzyme changes during development in amphibians was carried out by Chen (1968). He compared proteins extracted from embryonic, larval, and adult stages of three species, Bombina variegata, Rana temporaria, and Triturus alpestris, and identified subunits of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), and glucose-6-phosphate dehydrogenase (G6PDH).

Isoenzymes (or isozymes) are a group of enzymes that catalyze the same reaction but have different enzyme forms and catalytic efficiencies. All living systems apparently require multiple molecular forms of certain enzymes in order to maximize biological capacity. In a restricted definition, “isozymes” are different in genetic origins. The enzymes that have epigenetic differences due to differential precursor processings, covalent modifications, and tissue distributions are then called isoforms.

Isoenzymes (also called isozymes) are alternative forms of the same enzyme activity that exist in different proportions in different tissues. Isoenzymes differ in amino acid composition and sequence and multimeric quaternary structure; mostly, but not always, they have similar (conserved) structures. Their expression in a given tissue is a function of the regulation of the gene for the respective subunits

Isozymes arise from gene duplications and/or different epigenetic modifications of a gene product(s). In this sense, most of the recombinant enzymes with deletion, insertion, and/or other mutations at the genetic level fall into the category of isozymes. An example is the human alkaline phosphatases which have at least three different genetic origins, i.e., for placental, intestinal, and liver/bone/kidney enzymes are encoded by the same gene but differentially modified in a tissue-specific manner. Most circulating ALP is the hepatic isozyme, followed by the bone isoenzyme. Very little intestinal ALP is in circulation. Placental form is present only in late pregnancy.

Causes of Abnormally High Levels

Hepatic isoenzyme: Increased mostly with cholestatic diseases. Inducible with excessive stress, pituitary pars intermedia dysfunction (equine Cushing's disease) or corticosteroid therapy

Bone isoenzyme: Increased with increased osteoblastic activity (young growing animals, bony lysis, proliferative bone lesions, primary or secondary hyperparathyroidism)

Placental isoenzyme: is normally expressed by the placenta during gestation Increases in alkaline phosphatase in pregnancy are usually twice the upper limit of normal. Elevations above normal are due to late pregnancy

Lactate dehydrogenase is an enzyme that is present in almost all body tissues. Conditions that can cause increased LDH in the blood may include liver disease, anemia, heart attack, bone fractures, muscle trauma, cancers, and infections such as encephalitis, meningitis, encephalitis, and HIV. LDH exists in 5 isoenzymes. Each isoenzyme has a slightly different structure and is found in different concentrations in different tissues. For example, LDH-1 is found mostly in red blood cells and heart muscle. LDH-3 is concentrated in the lungs, although it is also found in other tissues. When LDH isoenzymes spill into your blood, it indicates damaged or diseased tissue. The results may tell your healthcare providers which tissue may be damaged or injured. LDH isozymes consist of two genetically distinct polypeptide chains, A (or M for muscle type) and B (or H for heart type), which form varying combinations of tetrameric structures.

Normal ratios are:

• LDH-1 less than LDH-2
• LDH-5 less than LDH-4

When LDH-1 is greater than your LDH-2, it could mean that we have anemia called flipped LDH because normally your LDH-2 is higher than your LDH-1.

When your LDH-5 is greater than your LDH-4 it could mean liver damage or liver disease. This includes cirrhosis and hepatitis.

There are many isozymes that are also act as regulators of mebloism or metabolic pathways the best example is hexokinase

A hexokinase is an enzyme that irreversibly phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate. Four distinct isozymes of hexokinase are reported e.g., The human genome contains four genes encoding distinct hexokinase isoenzymes, named HK1 to HK4 (HK4 is also known as glucokinase or GCK) HK (I, II, III, and IV) are found at different levels throughout the body and each form displays unique functional characteristics

• Hexokinase I/A is found in all mammalian tissues, and is considered a "housekeeping enzyme," unaffected by most physiological, hormonal, and metabolic changes.
• Hexokinase II/B constitutes the principal regulated isoenzyme in many cell types and is increased in many cancers. It is the hexokinase found in muscle and heart. Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP. The relative specific activity of hexokinase II increases with pH at least in a pH range from 6.9 to 8.5.
• Hexokinase III/C is substrate-inhibited by glucose at physiological concentrations. Little is known about the regulatory characteristics of this isoenzyme.

·         Mammalian hexokinase IV, also referred to as glucokinase, differs from other hexokinases in kinetics and functions.

·         Glucokinase can only phosphorylate glucose if the concentration of this substrate is high enough. It is half-saturated at glucose concentrations 100 times higher than those of hexokinases I, II, and III. Hexokinase IV is monomeric, about 50kDa, displays positive cooperativity with glucose, and is not allosterically inhibited by its product, glucose-6-phosphate.^[4]