Biology:Hepatic fructokinase

From HandWiki
Short description: Class of enzymes
ketohexokinase (fructokinase)
Ketohexokinase homodimer, Human
Identifiers
SymbolKHK
NCBI gene3795
HGNC6315
OMIM229800
RefSeqNM_006488
UniProtP50053
Other data
EC number2.7.1.3
LocusChr. 2 p23.3-23.2
Ketohexokinase
Identifiers
EC number2.7.1.3
CAS number9030-50-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

Hepatic fructokinase (or ketohexokinase) is an enzyme that catalyzes the phosphorylation of fructose to produce fructose-1-phosphate.

ATP + Fru  ⟶  ADP + F1P
ATP + D-fructose → ADP + D-fructose-1-phosphate[1]

Isoforms

In humans, ketohexokinase is encoded by the KHK gene, which produces two isoforms, KHK-A and KHK-C, through alternative splicing.

  • KHK-C is primarily expressed in the liver, kidney, and intestine. It has a high affinity for fructose (low Km) and is responsible for the majority of fructose metabolism.
  • KHK-A is ubiquitously expressed in many tissues at low levels. It has a significantly lower affinity for fructose (high Km) compared to the C isoform.[2]

Role in fructose metabolism

Ketohexokinase catalyzes the first step of fructolysis by phosphorylating fructose to form fructose 1-phosphate. The resulting fructose 1-phosphate is subsequently cleaved by aldolase B, producing intermediates that enter central carbohydrate metabolism.[3]

In humans, the KHK-C isoform is responsible for most fructose metabolism in the liver, kidney, and intestine. Unlike glucose metabolism, fructose metabolism through ketohexokinase bypasses phosphofructokinase, a major regulatory step in glycolysis, allowing fructose to enter downstream metabolic pathways through fructolysis.[4]

References