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Is Membrane Transport of FFA Mediated by Lipid, Protein, or Both?

	Points of Agreement

Top Points of Agreement Points of Disagreement Fatty Acid Nomenclature: A...

 

1. The movement of long-chain fatty acids across the plasma membrane is likely facilitated by membrane-associated proteins.
   
2. The exact molecular mechanisms of this protein-facilitated movement across the plasma membrane are not fully understood.
   
3. A number of membrane-associated proteins involved in facilitating the uptake of fatty acids into metabolically important tissues have been identified (i.e., FAT/CD36, FABPpm, FATP1–6). However, at this point, it is not clear as to 1) why there are so many different proteins, 2) whether they directly interact with each other, 3) whether some or all of these proteins enhance uptake through means (e.g., esterification or oxidation) other than transport, or 4) whether they associate with other proteins to channel fatty acids to different metabolic fates.
   
4. In heart and muscle, physiological stimuli (insulin, contraction) induce the translocation of FABPpm and/or FAT/CD36 from an endosomal pool to the plasma membrane, resulting in an increased rate of fatty acid uptake. Evidence for endocrine (insulin) regulation of adipocyte fatty acid uptake remains contradictory.
   
5. It cannot be discounted that other proteins or groups of proteins participate in the transmembrane transport of fatty acids, particularly in adipose tissue where the roles of known fatty acid transport proteins remain elusive.
   
6. Given the very different metabolic roles of muscle tissues and adipose tissue, it would not be surprising if, in these tissues, the fatty acid transport system and its regulation differ considerably.
   

	Points of Disagreement

Top Points of Agreement Points of Disagreement Fatty Acid Nomenclature: A...

 

1. The role of FAT/CD36 and FABPpm in mediating transport of long-chain fatty acids across membranes. Bonen et al. find that FAT/CD36 and FABPpm mediate fatty acid transport into giant sarcolemmal vesicles, whereas Kampf and Kleinfeld conclude that neither FAT/CD36 nor FABPpm mediate membrane transport of long-chain fatty acids in adipocyte cell lines.
   
2. The role of lipid phase (diffusion) and protein-mediated mechanisms in the membrane transport of long-chain fatty acids. Bonen et al. find evidence for a small contribution by a lipid phase (diffusion) mechanism and a quantitatively larger protein-mediated mechanism in giant sarcolemmal vesicles, whereas Kampf and Kleinfeld conclude that fatty acids transport in adipocytes occurs solely through a protein-mediated mechanism.
   
3. Whether inhibitors of fatty acid transport have been identified. Kampf and Kleinfeld have not observed transport inhibition in adipocytes, whereas Bonen et al find that specific reagents inhibit fatty acid transport across the plasma membrane of giant sarcolemmal vesicles.
   
4. Whether cells can be washed without removing the bulk of the unesterified fatty acids. Kampf and Kleinfeld have found that washing cells removes virtually all unesterified fatty acid from adipocytes, whereas Bonen et al. find that the bulk of the transported fatty acids observed after washing remains unesterified.
   

	Fatty Acid Nomenclature: A Source of Confusion.

Top Points of Agreement Points of Disagreement Fatty Acid Nomenclature: A...

 
In papers dealing with fatty acids and their derivatives, as in the present Point/ Counterpoint, there is a considerable lack of uniformity in the terms used to designate these molecules (Glatz and van der Vusse. Trends Biochem Sci 13: 167–168, 1988). For example, the term "free fatty acid" is often used to refer to nonesterified fatty acids, which is itself an ambiguous term because a fatty acid is by definition not esterified. A more accurate term for the covalently modified fatty acid found in, for example, triacylglycerols is "fatty ester," as recommended by the IUPACIUB. An additional problem is that the fatty acid may be solubilized in the aqueous phase or bound to a macromolecule such as a protein or a membrane. Glatz and van der Vusse have proposed the designation "fatty acid" (FA) for the aqueous phase form (also known as unbound FA) and protein (macromolecule)-bound FA for the nonaqueous form. Bonen et al. have used this nomenclature. To emphasize the direct measurement of the aqueous form of the FA, Kampf and Kleinfeld have designated the aqueous FA as FFA_u and have used the term FFA to designate the sum of the noncovalently bound and unbound FA. Another complication is that the aqueous FA at neutral pH is largely ionized (and therefore not an acid), whereas the macromolecular bound FA may be either ionized or protonated. Both sides of this Point/Counterpoint discussion agree that the nomenclature proposed by Glatz and van der Vusse represents a consistent and more accurate terminology than is currently in general use.

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				CORRIGENDA Physiology, August 1, 2007; 22(4): 295 - 295. [Full Text] [PDF]

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