MGSSHHHHHH SSGLVPRGSH MTHEEHHAAK TLGIGKAIAV LTSGGDAQGM NAAVRAVVRV GIFTGARVFF VHEGYQGLVD GGDHIKEATW ESVSMMLQLG GTVIGSARCK DFREREGRLR AAYNLVKRGI TNLCVIGGDG SLTGADTFRS EWSDLLSDLQ KAGKITDEEA TKSSYLNIVG LVGSIDNDFC GTDMTIGTDS ALHRIMEIVD AITTTAQSHQ RTFVLEVMGR HCGYLALVTS LSCGADWVFI PECPPDDDWE EHLCRRLSET RTRGSRLNII IVAEGAIDKN GKPITSEDIK NLVVKRLGYD TRVTVLGHVQ RGGTPSAFDR ILGSRMGVEA VMALLEGTPD TPACVVSLSG NQAVRLPLME CVQVTKDVTK AMDEKKFDEA LKLRGRSFMN NWEVYKLLAH VRPPVSKSGS HTVAVMNVGA PAAGMNAAVR STVRIGLIQG NRVLVVHDGF EGLAKGQIEE AGWSYVGGWT GQGGSKLGTK RTLPKKSFEQ ISANITKFNI QGLVIIGGFE AYTGGLELME GRKQFDELCI PFVVIPATVS NNVPGSDFSV GADTALNTIC TTCDRIKQSA AGTKRRVFII ETMGGYCGYL ATMAGLAAGA DAAYIFEEPF TIRDLQANVE HLVQKMKTTV KRGLVLRNEK CNENYTTDFI FNLYSEEGKG IFDSRKNVLG HMQQGGSPTP FDRNFATKMG AKAMNWMSGK IKESYRNGRI FANTPDSGCV LGMRKRALVF QPVAELKDQT DFEHRIPKEQ WWLKLRPILK ILAKYEIDLD TSDHAHLEHI TRKRSGEAAV.
Humans have three isozymes of phosphofructokinase: muscle, liver, and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, with the tetramer composition varying depending on the tissue type . The muscle-type isozyme, encoded by the PFKM gene, is specifically adapted to meet the high energy demands of muscle tissue .
The PFKM gene is located on chromosome 12 and encodes the muscle-type isozyme of phosphofructokinase. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease . This disease is characterized by an inability to properly break down glycogen, leading to muscle weakness and cramps during exercise .
Recombinant human PFKM is produced using baculovirus-insect cell expression systems. This method allows for the production of high-purity enzyme, which is essential for research and therapeutic applications . The recombinant enzyme retains the functional properties of the native enzyme, making it a valuable tool for studying glycolysis and related metabolic pathways .
PFKM plays a pivotal role in glycolysis by catalyzing the conversion of fructose-6-phosphate and ATP into fructose-1,6-bisphosphate and ADP . This reaction is the first committing step of glycolysis, meaning it is a point of no return in the pathway, committing the cell to metabolize glucose for energy production .
Mutations in the PFKM gene can lead to metabolic disorders such as glycogen storage disease type VII. This condition results in an accumulation of glycogen in muscle tissues, causing symptoms like muscle cramps, weakness, and exercise intolerance . Understanding the function and regulation of PFKM is crucial for developing therapeutic strategies for these metabolic disorders.