Hepatic fructokinase
| ketohexokinase (fructokinase) | |||||||
|---|---|---|---|---|---|---|---|
Ketohexokinase homodimer, Human | |||||||
| Identifiers | |||||||
| Symbol | KHK | ||||||
| NCBI gene | 3795 | ||||||
| HGNC | 6315 | ||||||
| OMIM | 229800 | ||||||
| RefSeq | NM_006488 | ||||||
| UniProt | P50053 | ||||||
| Other data | |||||||
| EC number | 2.7.1.3 | ||||||
| Locus | Chr. 2 p23.3-23.2 | ||||||
| |||||||
| Ketohexokinase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 2.7.1.3 | ||||||||
| CAS no. | 9030-50-6 | ||||||||
| Databases | |||||||||
| BRENDA | enzyme data | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | enzyme entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| Rhea | reactions | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Hepatic fructokinase (or ketohexokinase) is an enzyme that catalyzes the phosphorylation of fructose to produce fructose-1-phosphate.
Isoforms
[edit]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
[edit]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
[edit]- ↑ Bais R, James HM, Rofe AM, Conyers RA (1985). "The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol". Biochem. J. 230 (1): 53–60. doi:10.1042/bj2300053. PMC 1152585. PMID 2996495.
- ↑ Diggle CP, Shires M, Leitch D, Brooke D, Carr IM, Markham AF, Hayward BE, Asipu A, Bonthron DT (2009). "Ketohexokinase: Expression and Localization of the Principal Fructose-metabolizing Enzyme". Journal of Histochemistry & Cytochemistry. 57 (8): 763–774. doi:10.1369/jhc.2009.953190. PMC 2713076. PMID 19365088.
- ↑ Iizuka, Katsumi (2023). "Recent Progress on Fructose Metabolism—Chrebp, Fructolysis, and Polyol Pathway". Nutrients. 15 (7): 1778. doi:10.3390/nu15071778. PMC 10096667. PMID 37049617.
- ↑ Mirtschink, Peter; Jang, Cholsoon; Arany, Zoltan; Krek, Wilhelm (2018). "Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease". European Heart Journal. 39 (26): 2497–2505. doi:10.1093/eurheartj/ehx518. PMC 6037111. PMID 29020416.
External links
[edit]- Hepatic+fructokinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)