Heart, fatty acid-binding proteins

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

T. M. O Regan, M. Pravda, C.K. O Sullivan and G.G. Guilbault, Development of a disposable immunosensor for the detection of human heart fatty-acid binding protein in human whole blood using screen-printed carbon electrodes, Talanta, 57 (2002) 501-510. 

A-FABP belongs to a large family of fatty acid binding proteins and selectivity against particularly the heart and muscle isoform (H-FABP) is considered important. Mice with a disruption of the gene encoding H-FABP have been reported to suffer from stress... 

Binas, B., et al.. Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization. FASEBJ, 1999,13, 805-812. 

Although there are published antibody-based methods for many of the kidney-specific proteins listed above, antibodies are not commercially available currently for many of them (specifically, KIM-1, CYR-61 and Pap Al). Where the antibodies are readily available, cross-reactivity across species has not always been established (these have in general been used only in human and/or rat). Heart and kidney specific isoforms of fatty acid binding protein exist that may cross-react in some species with the LFBP antibodies additionally, a-2 x-globulin, a normal component of male rat urine, is homologous to K-FABP and may cross-react with the antibodies to LFBP (for reviews see Emeigh Hart, 2005, Emeigh Hart and Kinter 2005). 

Heart fatty acid-binding protein HFABP 2.1 Zanotti et al. (1992)... 

Two immunosensors developed by O Regan et al. [89,90] have demonstrated their usefulness for the early assessment of acute myocardial infarction (AMI). Human heart fatty-acid binding protein (H-FABP) is a biochemical marker for the early assessment of AMI. The authors constructed an amperometric immunosensor for the rapid detection of H-FABP in whole blood. The sensor is based on a one-step, direct sandwich assay in which the analyte and an alkaline phosphatase (AP) labelled antibody are simultaneously added to the immobilized primary antibody, using two distinct monoclonal mouse anti-human H-FABP antibodies. The substrate p-amino-phenyl phosphate is converted to p-aminophenol by AP, and the current generated by its subsequent oxidation at +300 mV vs. Ag/AgCl is measured. The total assay time is 50 min, and the standard curve was linear between 4 and 250 ng ml . The intra- and inter-assay coefficients of variation were below 9%. No cross-reactivity of the antibodies was found with other early cardiac markers, and endogenous substances in whole blood did not have an... 

Fatty acid binding protein (FABP3) is a cytosolic protein recently reported to be more sensitive for detection of cardiac injury in humans with myocardial infarct or congestive heart failure (Mion et al. 2007 Niizeki et al. 2007). Flowever, FABP3 is also found, although in much lower concentrations, in muscle, brain, and kidney. As for CK and LD, its occurrence in skeletal muscle substantially diminishes its value as a cardiac biomarker because of the higher and variable background of mild skeletal muscle injury in laboratory animals. Its use as a cardiac biomarker would require exclusion of muscle injury and renal disease. 

Niizeki, T. et al. 2007. Heart-type fatty acid-binding protein is more sensitive than troponin T to detect the ongoing myocardial damage in chronic heart failure patients. Journal of Cardiac Failure 13 120-127. 

Fatty acid-binding proteins (FABPs) are a family of hydrophobic molecule transporters and play a pivotal role in cellular fatty acid transport in the cytosol and at the plasma membrane. At least nine FABPs have been identified and named after the tissues with which they were initially associated (Glatz and van der Vusse 1996 Glatz and Storch 2001 Zimmerman and Veerkamp 2002). Heart FABP (H-FABP) is found in cytoplasm of myocytes and these bind long chain fatty acids. These proteins may be markers of myocardial ischemia, but other FABPs are present in several other tissues. Liver FABP (L-FABP) occurs mainly in hepatocytes and also in smaller amounts in the kidney and small intestine (Bass et al. 1989). 

Muller-Fahmow, A., Egner, U., Jones, A., Riidel, H., Spener, R, Saenger, W. (1991). Three-dimensional structure of fatty acid binding protein from bovine heart, Eur. J. Biochem. 199 271. 

Richieri,G.V.,Ogata,R.T.,andKleinfeld,A.M., 1994,Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart and liver measured with the fluorescent probe ADIFAB, / Biol. Chem. 269 23918-23930. 

Maatman RG, van de Westerlo EM, van Kuppevelt TH, Veerkamp JH. (1992) Molecular identification of the hver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. Biochem J. 288(Pt l) 285-290. 

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mv 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel. 

The release of fatty acids from adipose tissue is regulated by the rate of hydrolysis of triacylglycerol and the rate of esterification of acyl-CoA with glycerol 3-phosphate. The rate of hydrolysis is stimulated by hormones that bind to cell-surface receptors and stimulate adenylate cyclase (which catalyzes the production of cAMP from ATP). Hormone-sensitive lipase (Sec. 13.4) can exist in two forms, one of which exhibits very low activity and a second which is phosphorylated and has high activity. Before hormonal stimulation of adenylate cyclase, the low-activity lipase predominates in the fat cell. Stimulation of protein kinase by an increase in cAMP concentration leads to phosphorylation of the low-activity lipase. An increase in the rate of hydrolysis of triacylglycerol and the release of fatty acids from the fat cell follows. This leads to a greater utilization of fatty acids by tissues such as heart, skeletal muscle, and liver. 

Ans. Serum albumin strongly binds 2 to 8 mol of fatty acids per molecule of protein. This is transported in the blood to the heart and skeletal muscles, which absorb and use it as a major souree of oxidative fuel. 

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