The cytoplasmic fatty-acid-binding proteins: thirty years and counting

The interest in fatty-acid-binding proteins has produced about 1000 research papers since their discovery nearly 30 years ago. This review provides an entry to the mammalian and nonmammalian literature through a compendium of categorized review articles (nearly 60). Publications that have not yet been reviewed, particularly of function and modes of action, are presented and discussed in light of earlier reports. This large protein family may be integral in the relationship between lipid and carbohydrate metabolism.     

Inhibition of high affinity uptake of GABA by branched fatty acids

Summary Several branched fatty acids including an antiepileptic agent nDPA were tested as potential inhibitors of high affinity uptake of GABA by brain slices and synaptosomes. Only three compounds (2-butyl-3-propylhexanoic acid, 5-propyloctanoic acid, 2-propylpenten-2-oic acid) were found to be relatively weak inhibitors of the uptake system. There was no correlation between anticonvulsant properties of the branched fatty acids and their potencies as inhibitors of high affinity uptake of GABA.     

The role of the lymph circulation in free fatty acid transport

Zusammenfassung Es wurde in der Leber- und Halslymphe des Hundes eine niedrigere Konzentration der freien Fettsäuren gefunden als im Blutplasma. Sie wird durch Noradrenalininfusion signifikant erhöht.     

The polycystins: a novel class of membrane-associated proteins involved in renal cystic disease

Polycystin-1, polycystin-2 and polycystin-L are the predicted protein products of the PKD1, PKD2 and PKDL genes, respectively. Mutations in PKD1 and PKD2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). This condition is one of the commonest mendelian disorders of man with a prevalence of 1:800 and is responsible for nearly 10% of cases of end-stage renal failure in adults. The cloning of PKD1 and PKD2 in recent years has provided the initial steps in defining the mechanisms underlying renal cyst formation in this condition, with the aim of defining pharmacological and genetic interventions that may ameliorate the diverse and often serious clinical manifestations of this disease. The PKD genes share regions of sequence similarity, and all predict integral membrane proteins. Whilst the predicted protein domain structure of polycystin-1 suggests it is involved in cell-cell or cell-matrix interactions, the similarity of polycystin-2 and polycystin-L to the pore-forming domains of some cation channels suggests that they all form subunits of a large plasma membrane ion channel. In the few years since the cloning of the PKD genes, a consensus that defines the range of mutations, expression pattern, interactions and functional domains of these genes and their protein products is emerging. This review will therefore attempt to summarise these data and provide an insight in to the key areas in which polycystin research is unravelling the mechanisms involved in renal cyst formation. Received 22 February 1999; received after revision 5 July 1999; accepted 6 July 1999     

The separation of fatty acids

Résumé Le problème de la séparation des acides gras est exposé en détail. Les méthodes physiques couramment appliquées à une macro- ou micro-échelle sont discutées et l'on donne des exemples tirés de la littérature ou de méthodes récemment utilisées dans les recherches. Celles-ci comprennent la cristallisation, la distillation fractionnée, la distribution par contre-courant, la chromatographie en phase gazeuse et la spectrographie de masse.

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Presented before the symposium on Chemistry and Physiology of Fats at the meeting of the Chemical Institute of Canada, Ottawa, October 9, 1957. Hormel Institute publication No. 168.     

Functions of fatty acid binding proteins

Summary Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14–15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABP_pm). These proteins have not been fully characterized to date, but strong evidence suggests that they function in the transport of long-chain fatty acids across the plasma membrane.     

Functions of fatty acid binding proteins

Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14-15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABPpm). These proteins have not been fully characterized to date, but strong evidence suggest that they function in the transport of long-chain fatty acids across the plasma membrane.     

Column chromatography of lipides: Odd-numbered straight-chain fatty acids of menhaden oil

Zusammenfassung Das Vorkommen vonn-Nona-,n-Hepta-,n-Penta- undn-Tridekansäure in Menhaden-Öl wird papierchromatographisch bewiesen. Die Säuren werden nach Hydrierung oder Oxydation geeigneter Fraktionen mit Hilfe der Säulenchromatographie isoliert, eine Trennung, die auf der Verteilung der Methylester zwischen Silikon-Öl und wässerigem Acetonitril beruht. Es werden die Anteile der gerad- und ungeradzahligen Säuren des Menhaden-Öles verglichen.

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This work has been supported by a research grant from the National Institutes of Health (USPHS RG 4226) and by the Hormel Foundation.     

Regulation of SNARE fusion machinery by fatty acids

Vesicle fusion is a ubiquitous biological process involved in membrane trafficking and a variety of specialised events such as exocytosis and neurite outgrowth. The energy to drive biological membrane fusion is provided by fusion proteins called SNAREs. Indeed, SNARE proteins play critical roles in neuronal development as well as neurotransmitter and hormone release. SNARE proteins form a very tight alpha-helical bundle that can pull two membranes together, thereby initiating fusion. Whereas a great deal of attention has been paid to partner proteins that can affect SNARE function, recent genetic and biochemical evidence suggests that local lipid environment may be as important in SNARE regulation. Direct lipid modification of SNARE fusion proteins and their regulation by fatty acids following phospholipase action will be discussed here in detail. Our analysis highlights the fact that lipids are not a passive platform in vesicle fusion but intimately regulate SNARE function. Received 20 December 2006; received after revision 6 February 2007; accepted 15 March 2007     

Table of replaceable amino acids in proteins

Zusammenfassung Auf Grund vorausgegangener Experimente, besonders über degenerierte Triplettcodons, wird ein Verfahren entwickelt, aus dem sich die Austauschmöglichkeiten von Aminosäuren in Eiweißstoffe ergeben, dann nämlich, wenn im Codon nur je eine Base des Tripletts ersetzt wird.     

The effect of colchicine on plasma unesterified fatty acids

Zusammenfassung Die Verabereichung einer letalen Dosis Colchicin verursacht u. a. eine Zunahme der unveresterten Fettsäuren und eine Abnahme des Körpergewichts. Der Gehalt an veresterten Fettsäuren, freiem und verestertem Cholesterin und Plasmaeiweissen bleibt unverändert, ebenso Hämatokrit-und Hämoglobinwerte.

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Supported by the National Heart Institute, Bethesda, Md.