About Hexokinase :
A hexokinase is an enzyme that phosphorylates hexoses, which are sugars with six carbons, resulting in hexose phosphate. Glucoseis is the most important substrate of hexokinases in most organisms, while glucose-6-phosphate is the most important product. Hexokinase is able to transfer an inorganic phosphate group from ATP to a substrate. There are genes that encode hexokinase in every domain of life. They can be found in bacteria, plants and vertebrates, including humans. More than one isoform or isozyme can occur in one species, providing different functions. Hexokinases are actin fold proteins and share a common ATP binding site core surrounded by more variable sequences.
When a hexose is phosphorylated it is often limited to several intracellular metabolic processes. The phosphorylated hexoses are charges so they can not be transported out of a cell as easily.
Mammalian hexokinase isozymes have four important forms. These isozymes have different subcellular locations and movements, as well as physiological functions. They are known as hexokinases I, II, III and IV, or A, B, C and D. The first three are called low-K isozymes due to their high affinity for glucose. They are inhibited by their product glucose-6-phosphate. Hexokinase I is present in all mammalian tissues and is not affected by most changes, whether physiological, hormonal or metabolic. Hexokinase II is the principal regulated isoform in many cell types, and is in the muscle and heart, as well as in the mitochondria outer membrane. It is seen in increased amounts in many cancers. Less is known about hexokinase III and its regulatory characteristics but it is substrate-inhibited by glucose at physiologic concentrations.
Hexokinase IV in mammals, which is also called glucokinase, has different kinetics and functions compared to other hexokinases. When it translocates between cytoplasm and nucleus of liver cells is the location of the phosphorylation on a subcellular level occurs. The concentration of the substrate needs to be high enough for glucokinase to phosphorylate glucose. Hexokinase IV displays positive cooperativity with glucose and is not inhibited by glucose-6-phosphate, unlike hexokinases I, II and III. It is found in the liver, pancreas, hypothalamus and small intestine. It might also be present in other neuroendocrine cells. It helps to regulate carbohydrate metabolism and also helps to control insulin release by acting as a glucose sensor in the beta cells of the pancreatic islets, as well as controlling glucagon release in alpha cells. It also controls the levels of glycogen synthesis in hepatocytes of the liver.
Through specific binding to a porin or voltage dependent anion channel, hexokinases I and II can associate physically to the outer surface of the external membrane of the mitochondria. This gives hexokinase direct access to ATP that the mitochondria generates. Mitochondrial hexokinase can be observed in elevated amounts, up to 200 times more than in normal tissues, in growing malignant tumor cells.
Hexokinase deficiency causes Chronic Haemolytic Anaemia, which is caused by a mutation to the HK gene. This gene codes for the HK enzyme and the mutation leads to less HK activity, which causes hexokinase deficiency.