|
Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes () of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory and rate limiting steps of glycolysis. PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell’s energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin.〔 == Structure == Mammalian PFK1 is a 340kd〔 tetramer composed of three types of subunit: muscle (M), liver (L), and platelet (P). The composition of the PFK1 tetramer differs according to the tissue type it is present in. For example, mature muscle expresses only the M isozyme, therefore, the muscle PFK1 is composed solely of homotetramers of M4. The liver and kidneys express predominantly the L isoform. Erythrocytes express both M and L subunits which randomly tetramerize to form M4, L4 and the three hybrid forms of the enzyme (ML3, M2L2, M3L). As a result, the kinetic and regulatory properties of the various isoenzymes pools are dependent on subunit composition. Tissue-specific changes in PFK activity and isoenzymic content contribute significantly to the diversities of glycolytic and gluconeogenic rates which have been observed for different tissues.〔 PFK1 is an allosteric enzyme and has a structure similar to that of hemoglobin insofar as it is a dimer of a dimer.〔; 〕 One half of each dimer contains the ATP binding site whereas the other half the substrate (fructose-6-phosphate or (F6P)) binding site as well as a separate allosteric binding site.〔 Each subunit of the tetramer is 319 amino acids and consists of two domain, one that binds the substrate ATP, and the other that binds fructose-6-phosphate. Each domain is a b barrel, and has cylindrical b sheet surrounded by alpha helices. On the opposite side of the each subunit from each active site is the allosteric site, at the interface between subunits in the dimer. ATP and AMP compete for this site. The N-terminal domain has a catalytic role binding the ATP, and the C-terminal has a regulatory role 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Phosphofructokinase 1」の詳細全文を読む スポンサード リンク
|