In Vivo Metabolism of [1,6-13C2]Glucose Reveals Distinct Neuroenergetic Functionality between Mouse Hippocampus and Hypothalamus

Glucose is a major energy fuel for the brain, however, less is known about specificities of its metabolism in distinct cerebral areas. Here we examined the regional differences in glucose utilization between the hypothalamus and hippocampus using in vivo indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) upon infusion of [1,6-13C2]glucose. Using a metabolic flux analysis with a 1-compartment mathematical model of brain metabolism, we report that compared to hippocampus, hypothalamus shows higher levels of aerobic glycolysis associated with a marked gamma-aminobutyric acid-ergic (GABAergic) and astrocytic metabolic dependence. In addition, our analysis suggests a higher rate of ATP production in hypothalamus that is accompanied by an excess of cytosolic nicotinamide adenine dinucleotide (NADH) production that does not fuel mitochondria via the malate-aspartate shuttle (MAS). In conclusion, our results reveal significant metabolic differences, which might be attributable to respective cell populations or functional features of both structures.

Small Genomes and Sparse Metabolisms of Sediment-Associated Bacteria from Four Candidate Phyla

ABSTRACTCultivation-independent surveys of microbial diversity have revealed many bacterial phyla that lack cultured representatives. These lineages, referred to as candidate phyla, have been detected across many environments. Here, we deeply sequenced microbial communities from acetate-stimulated aquifer sediment to recover the complete and essentially complete genomes of single representatives of the candidate phyla SR1, WWE3, TM7, and OD1. All four of these genomes are very small, 0.7 to 1.2 Mbp, and have large inventories of novel proteins. Additionally, all lack identifiable biosynthetic pathways for several key metabolites. The SR1 genome uses the UGA codon to encode glycine, and the same codon is very rare in the OD1 genome, suggesting that the OD1 organism could also transition to alternate coding. Interestingly, the relative abundance of the members of SR1 increased with the appearance of sulfide in groundwater, a pattern mirrored by a member of the phylumTenericutes. All four genomes encode type IV pili, which may be involved in interorganism interaction. On the basis of these results and other recently published research, metabolic dependence on other organisms may be widely distributed across multiple bacterial candidate phyla.IMPORTANCEFew or no genomic sequences exist for members of the numerous bacterial phyla lacking cultivated representatives, making it difficult to assess their roles in the environment. This paper presents three complete and one essentially complete genomes of members of four candidate phyla, documents consistently small genome size, and predicts metabolic capabilities on the basis of gene content. These metagenomic analyses expand our view of a lifestyle apparently common across these candidate phyla.

The apicoplast: a red alga in human parasites

Surprisingly, some of the world's most dangerous parasites appear to have had a benign photosynthetic past in the ocean. The phylum Apicomplexa includes the causative agents of malaria and a number of additional human and animal diseases. These diseases threaten the life and health of hundreds of millions each year and pose a tremendous challenge to public health. Recent findings suggest that Apicomplexa share their ancestry with diatoms and kelps, and that a key event in their evolution was the acquisition of a red algal endosymbiont. A remnant of this endosymbiont is still present today, albeit reduced to a small chloroplast-like organelle, the apicoplast. In the present chapter, I introduce the remarkably complex biology of this organelle. The apicoplast is bounded by four membranes, and these membranes trace their ancestry to three different organisms. Intriguingly, this divergent ancestry is still reflected in their molecular makeup and function. We also pursue the raison d'être of the apicoplast. Why did Apicomplexa retain a chloroplast when they abandoned photosynthesis for a life as obligate parasites? The answer to this question appears to lie in the profound metabolic dependence of the parasite on its endosymbiont. This dependence may prove to be a liability to the parasite. As humans lack chloroplasts, the apicoplast has become one of the prime targets for the development of parasite-specific drugs.