Phosphofructokinase muscle

V8. Vasconcelos, O., Sivakumar, K., Dalakas, M. C., Quezado, M., Nagle, J., Leon-Monzon, M., Dubnick, M., Gajdusek, C., and Goldfarb, L. G., Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenzai Jewish patients with Tarui disease. Proc. Natl Acad. Sci. U.S.A. 92, 10322-10326 (1995). 

Phosphofructokinase, muscle ttype Enriched in amyloid plaques Liao et al. 2004... 

VII Phosphofructokinase Muscle Increased amount normal structure. Like type V. 

A decreased glycolytic rate has been proposed as a cause of muscle fatigue and related to pH inhibition of glycolytic enzymes. Decreasing pH inhibits both phosphorylase kinase and phosphofructokinase (PFK) activities. PFK is rate determining for glycolytic flux and therefore must be precisely matched to the rate of ATP expenditure. The essential characteristic of PFK control is allosteric inhibition by ATP. This inhibition is increased by H and PCr (Storey and Hochachka, 1974 ... 

Bock, P.E. Frieden, C. (1976). Phosphofructokinase I. Mechanism ofpH-dependent inactivation and reactivation of the rabbit muscle enzyme. II. Role of ligands in pH-dependent structural changes of the rabbit muscle enzyme. J. Biol. Chem. 251, 5630-5643. 

Storey, K.B. Hochachka, P.W. (1974). Activation of muscle glycolysis A role for creatine phosphate in phosphofructokinase regulation. FEES Lett. 46, 337-339. 

Type VII Tarul s disease Deficiency of phosphofructokinase in muscle and erythrocytes As for type V but also possibility of hemolytic anemia. 

Phosphofructokinase (PFK) is a key regulatory enzyme of glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-diphosphate. The active PFK enzyme is a homo- or heterotetrameric enzyme with a molecular weight of 340,000. Three types of subunits, muscle type (M), liver type (L), and fibroblast (F) or platelet (P) type, exist in human tissues. Human muscle and liver PFKs consist of homotetramers (M4 and L4), whereas red blood cell PFK consists of five tetramers (M4, M3L, M2L2, ML3, and L4). Each isoform is unique with respect to affinity for the substrate fructose-6-phosphate and ATP and modulation by effectors such as citrate, ATP, cAMP, and fructose-2,6-diphosphate. M-type PFK has greater affinity for fructose-6-phosphate than the other isozymes. AMP and fructose-2,6-diphosphate facilitate fructose-6-phosphate binding mainly of L-type PFK, whereas P-type PFK has intermediate properties. 

HI. Hamaguchi, T Nakajima, H., Noguchi, T., Ono, A., Kono, N., Tarui, S., Kuwajima, M., and Matsuzawa, Y., A new variant of muscle phosphofructokinase deficiency in a Japanese case with abnormal splicing. Biochem. Biophys. Res. Commun. 202,444-449 (1994). 

N2. Nakajima, H., Kono, N Yamasaki, T Hotta, K., Kawachi, M Kuwajima, M., Noguchi, T., Tanaka, T., and Tarui, S Genetic defect in muscle phosphofructokinase deficiency Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5 -splice site. J. Biol. Chem. 265, 9392-9395 (1990). 

T14. Tarui, S., Okuno, G., Ikuno, Y Tanaka, T Suda, M and Nishikawa, M., Phosphofructokinase deficiency in skeletal muscle. A new type of glycogenesis. Biochem. Biophys. Res. Commun. 19,517-523(1965). 

T23. Tsujino, S Servidei, S Tonin, P., Shanske, S., Azan, G., and DiMauro, S., Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency. Am. J. Hum. Genet. 54,812-819 (1994). 

The increase in proton concentration in the muscle decreases the activities of two key enzymes, which regulate the flux through glycolysis phosphorylase and phosphofructokinase (Chapter 13) (Figure 6.7). 

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

Fig. 8. A pictorial representation of the monomer, dimer, and tetrameric structures of rabbit muscle phosphofructokinase as deduced from electron microscopy.

Phosphofructokinase is the enzyme deficient in glycolysis leading to glycogenosis type VII (GSD VII, M. Tarui, MIM 232 800). The enzyme in its active form is a tetra-mer, composed of three different subunits M (muscle), L (liver), and P or F (platelets, fibroblasts). The enzyme is found in different compositions in different tissues, as shown in Table 4.6.16. In glycogenosis type VII the enzyme deficiency can only be determined in muscle, because only the deficiency of the M form leads to GSD VII. 

King RF, Macfie J, Hill G (1981) Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients. Clin Sci 60 451-456... 

Figure 11-2 Roles of phosphofructose kinase and fructose 1,6-bisphosphatase in the control of the breakdown and storage (—+) of glycogen in muscle. The uptake of glucose from blood and its release from tissues is also illustrated. The allosteric effector fructose 2,6-bisphosphate (Fru-2,6-P2) regulates both phosphofructokinase and fructose 2,6-bisphosphatase. These enzymes are also regulated by AMP if it accumulates. The activity of phosphofructokinase-2 (which synthesizes Fru-2,6-P2) is controlled by a cyclic AMP-dependent kinase and by dephosphorylation by a phosphatase.

It has been proposed that the substrate cycle involving phosphofructokinase and fructose bisphosphatase is used by bumblebees to warm their flight muscles to 30°C before flight begins. 

Substrate cycles generate heat, a property that is apparently put to good use by cold bumblebees whose thoracic temperature must reach at least 30°C before they can fly. The insects apparently use the fructose bisphosphatase-phosphofructokinase substrate cycle (Fig. 11-2, steps b and c) to warm their flight muscles.268 It probably helps to keep us warm, too. 

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