Phosphorylation of the lipid droplet localized glycerol­3­phosphate acyltransferase Gpt2 prevents a futile triacylglycerol cycle in yeast.

The proteome of lipid droplets, storage compartments of triacylglycerols (TAGs), comprises TAG synthesizing and TAG degrading enzymes. Thus, to prevent a futile cycle the activity of enzymes catalyzing key steps in TAG turnover has to be strictly coordinated. The first and committed reaction of TAG synthesis is catalyzed by a glycerol­3­phosphate acyltransferase (GPAT). Here we demonstrate that in the model organism yeast the lipid droplet associated GPAT Gpt2 requires phosphorylation at a conserved motif to prevent a futile TAG cycle. Phosphorylation deficiency at the conserved motif increases the enzyme activity of Gpt2 and consequently enhances TAG synthesis. In proliferating cells the phosphorylation deficient GPAT-form contributes to TAG metabolism similar to control. However, during lipolysis the increased activity of phosphorylation deficient Gpt2 causes a constant TAG level by using TAG-released fatty acids as substrate for TAG synthesis. These data strongly indicate that phosphorylation of Gpt2 at a conserved motif plays a critical role in coordinating the synthesis and degradation of TAGs.

Phylogenetic analysis of glycerol 3-phosphate acyltransferases in opisthokonts reveals unexpected ancestral complexity and novel modern biosynthetic components.

Glycerolipid synthesis represents a central metabolic process of all forms of life. In the last decade multiple genes coding for enzymes responsible for the first step of the pathway, catalyzed by glycerol 3-phosphate acyltransferase (GPAT), have been described, and characterized primarily in model organisms like Saccharomyces cerevisiae and mice. Notoriously, the fungal enzymes share low sequence identity with their known animal counterparts, and the nature of their homology is unclear. Furthermore, two mitochondrial GPAT isoforms have been described in animal cells, while no such enzymes have been identified in Fungi. In order to determine if the yeast and mammalian GPATs are representative of the set of enzymes present in their respective groups, and to test the hypothesis that metazoan orthologues are indeed absent from the fungal clade, a comparative genomic and phylogenetic analysis was performed including organisms spanning the breadth of the Opisthokonta supergroup. Surprisingly, our study unveiled the presence of 'fungal' orthologs in the basal taxa of the holozoa and 'animal' orthologues in the basal holomycetes. This includes a novel clade of fungal homologues, with putative peroxisomal targeting signals, of the mitochondrial/peroxisomal acyltransferases in Metazoa, thus potentially representing an undescribed metabolic capacity in the Fungi. The overall distribution of GPAT homologues is suggestive of high relative complexity in the ancestors of the opisthokont clade, followed by loss and sculpting of the complement in the descendent lineages. Divergence from a general versatile metabolic model, present in ancestrally deduced GPAT complements, points to distinctive contributions of each GPAT isoform to lipid metabolism and homeostasis in contemporary organisms like humans and their fungal pathogens.

Head shape measurement standards and cranial orthoses in the treatment of infants with deformational plagiocephaly.

This review aims to determine how head shape is measured and describes the use of orthoses in the management of deformational plagiocephaly. A systematic review was conducted and papers published in English up to and including 2006 were sourced from nine databases. After initial screening, 20 papers were included; three literature reviews and 17 original papers. Of the original papers, eight concerned the method of head shape measurement. Measurements are important in determining clinical classification and treatment modality of deformational plagiocephaly. All studies were appraised and assigned a level of evidence according to the Scottish Intercollegiate Guidelines Network. Methodological quality was inadequate. Publications involving the use of cranial orthoses used convenience samples, were not blinded, and used different measurement techniques. No comparison groups were included and participants were not randomized. Evidence suggests that conservative treatments might reduce skull deformity although the quality is poor. Clinical studies investigating the use of cranial orthoses reported beneficial effects. Further research is required to identify the efficacy of cranial orthoses in the treatment of deformational plagiocephaly based on a standardized measurement technique to facilitate classification of this condition.