Abstract
Fatty acids (FAs) are a highly diverse class of molecules that can have variable chain length, number of double bonds and hydroxylation sites. FAs with 22 or more carbon atoms are described as very long chain fatty acids (VLCFAs). VLCFAs are synthesized in the endoplasmic reticulum (ER) through a four-step elongation cycle by membrane embedded enzymes. VLCFAs are precursors forthe synthesis of sphingolipids (SLs) and glycerophospholipids. Besides their role as lipid constituents, VLCFAs are also found as precursors of lipid mediators. Mis-regulation of VLCFA metabolism can result in a variety of inherited diseases ranging from ichthyosis, to myopathies and demyelination. The enzymes for VLCFA biosynthesis are evolutionary conserved and many of the pioneering studies were performed in the model organism Saccharomyces cerevisiae. A growing body of evidence suggests that VLCFA metabolism is intricately regulated to maintain lipid homeostasis. In this review we will describe the metabolism of VLCFAs, how they are synthesized, transported and degraded and how these processes are regulated, focusing on budding yeast. We will review how lipid metabolism and membrane properties are affected by VLCFAs and which impact mutations in the biosynthetic genes have on physiology. We will also briefly describe diseases caused by mis-regulation of VLCFAs in human cells.
Highlights
Fatty acids (FAs) are a highly diverse class of molecules that can have variable chain length, number of double bonds and hydroxylation sites
FAs with 22 or more carbon atoms are described as very long chain fatty acids (VLCFAs)
SLs in yeast consist of a long chain base (LCB) that is synthesized from serine and palmitoyl-CoA by the serine palmitoyltransferase (SPT)
Summary
Fatty acids (FAs) are a highly diverse class of molecules that can have variable chain length, number of double bonds and hydroxylation sites. FAs with 22 or more carbon atoms are described as very long chain fatty acids (VLCFAs). This special FA sub-class is mainly incorporated into SLs and glycosylphosphatidylinositols (GPI)-anchored proteins but can be found in other lipid classes. As for many other processes, yeast as a model organism has been essential to identify the enzymes necessary for VLCFA biosynthesis, activation, regulation and degradation (Tehlivets et al 2007; Welch and Burlingame 1973). VLCFAs are synthesized from the products of de novo FA synthesis in the endoplasmic reticulum (ER) through a fourstep elongation cycle by membrane embedded enzymes. SLs in yeast consist of a long chain base (LCB) that is synthesized from serine and palmitoyl-CoA by the serine palmitoyltransferase (SPT).
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