Furthermore, 3-hydroxyacyl-CoA dehydrogenase is inhibited by NADH and thiolase is inhibited by acetyl-CoA, so that fatty acids wil not be oxidized when there are plenty of energy-yielding substrates in the cell.
Usually neurons use only glucose as energy source. Since the brain stores only a very small amount of glycogen, it needs a steady supply of glucose. During long fasts, it becomes able to oxidize ketone bodies.
The maintenance of a fairly steady concentration of glucose in the blood is one of the liver's main functions. This is accomplished through gluconeogenesis and glycogen synthesis and degradation. It synthesizes ketone bodies when acetyl-CoA is plenty. It is also the site of urea synthesis. It synthesizes fatty acids and stores them as triacylglycerols. Glucagon activates a hormone-sensitive lipase, which hydrolizes triacylglycerols yielding glycerol and fatty acids. These are then released into the bloodstream in lipoproteins.
It has also been suggested that histidine-containing small peptides could have been involved in the prebiotic formation of other peptides and nucleic acid molecules, once these monomers accumulated in primitive tidal lagoons or ponds Fani and Fondi and references therein. If primitive catalysts required histidine, then the eventual exhaustion of the prebiotic supply of histidine and histidine-containing peptides imposed a selective pressure favoring those microorganisms capable of synthesizing histidine.
How the his pathway originated remains an open question, but the analysis of the structure and organization as well as the phylogenetic analyses of the his genes in micro organisms belonging to different phylogenetic archaeal, bacterial, and eukaryal lineages reveals that different molecular mechanisms played an important role in shaping this pathway. Actually, an impressive series of well-documented duplication Fani et al. Therefore, the histidine biosynthetic pathway represents an excellent model for understanding the molecular mechanisms driving the assembly and refinement of metabolic routes.
Two of the histidine biosynthetic genes, hisA and hisF , are exceptionally interesting from an evolutionary viewpoint. The comparative analysis of the HisA and HisF proteins from different archaeal, bacterial, and eukaryotic micro organisms reveals that they are paralogous and share a similar internal organization into two paralogous modules half the size of the entire sequence Fani et al.
According to the model proposed, the first duplication involved an ancestral module half the size of the present-day hisA gene and led by a gene elongation event to the ancestral hisA gene which, in turn, underwent a duplication that gave rise to the hisF gene Fig. Since the overall structure of the hisA and hisF genes are the same in all known organisms, it is likely that they were part of the genome of the LUCA and that the two duplication events occurred long before its appearance.
The model proposed predicts Fani et al. Therefore, hisA and hisF represent a paradigmatic example of how evolution works at both the molecular and functional levels and represent a crossroad of different molecular mechanisms and hypotheses on the origin of metabolic pathways. Indeed, they are the result of gene elongation duplication and fusion and gene duplication events, which finally led to a large paralogous gene family TIM barrels. Besides, these structural events are strongly linked to the function performed by the enzymes.
The ancestral enzyme might have catalyzed different, even though similar, reactions in different metabolic routes i. Lastly, hisA and hisF also supported, even though partially, the Horowitz idea on the origin and evolution of metabolic pathways since they catalyze two sequential steps in the same biosynthetic route, are paralogous, and are arranged in tandem in the same operon. Evolutionary model proposed for the origin and evolution of his A and his F b. Recently Fani et al.
Data obtained allowed the reconstruction of the evolutionary history of three interesting gene fusions. Quite interestingly, it has been demonstrated that fusion events involving different histidine biosynthetic genes that gave rise to genes coding for bifunctional or multifunctional enzymes, such as hisNB , hisIE , and hisHF , occurred in different evolutionary timescales and in different micro organisms, and that they have very different phylogenetic distributions see below.
The whole body of data permitted the depiction of a likely scenario for the origin and evolution of histidine biosynthetic genes. According to the model proposed Fani et al. Concerning the organization of these genes in LUCA, it is not still possible to establish if they were 1 scattered throughout its genome, 2 organized in a single more-or-less compact operon, or 3 exhibited a mixed organization i.
However, it is quite clear that after the divergence from LUCA, the organization of histidine biosynthetic genes underwent several different rearrangements.
This suggests that the two elongation events as well as the paralogous duplication event leading to hisA and hisF are very ancient, i. During the early steps of molecular evolution, hisA and its copies underwent multiple duplication events leading to a paralogous gene family. The fusion between hisI and hisE occurred more than once in Bacteria, indicating a phenomenon of convergent evolution.
Moreover, this gene might have been horizontally transferred Fani et al. This fusion was parallel to the introgression of hisN into an already formed and more or less compact his operon. The fusions involving hisH and hisF were found only in two bacteria. Metabolic pathways of the earliest heterotrophic organisms arose during the exhaustion of the prebiotic compounds present in the primordial soup.
In the course of molecular and cellular evolution, different mechanisms and different forces might have concurred in the emergence of new metabolic abilities and the shaping of metabolic routes. However, duplication of DNA regions represents a major force of gene and genome evolution. In addition to this, gene fusion also played an important role in the construction and assembly of chimeric genes.
The dissemination of metabolic routes between micro-organisms might be facilitated by horizontal transfer events. The increasing frequency of protein phylogenies that are in conflict with the conventional universal tree Brown and Doolittle and the finding that the horizontal transfer of genetic information is pervasive among microbial lineages and that it may occur across different phylogenetic kingdoms Gogarten et al. The horizontal transfer of entire metabolic pathways or part thereof might have had a special role during the early stages of cellular evolution.
There are many different schemes that can be proposed for the emergence and evolution of metabolic pathways, depending on the available prebiotic compounds and the available enzymes previously evolved. Even though most data coming from the analysis of completely sequenced genomes and directed-evolution experiments strongly support the patchwork hypothesis, we do not think that all the metabolic pathways arose in the same manner.
In our opinion, the different schemes might not be mutually exclusive. However, other ancient pathways, including histidine biosynthesis, might be assembled using at least two different schemes Horowitz and Jensen. Histidine biosynthetic pathway and genes: structure, regulation and evolution. Microbiol Rev. Brilli M, Fani R. Molecular evolution of hisB genes. J Mol Evol. The origin and evolution of eukaryal HIS7 genes: from metabolon to bifunctional proteins?
Archaea and the prokaryote-to-eukaryote transition. Microbiol Mol Biol Rev. Clarke PH. The evolution of enzymes for the utilization of novel substrates. Cambridge: Cambridge University Press; Google Scholar. Copley RR, Bork P. Homology among betaalpha 8 barrels: implications for the evolution of metabolic pathways. J Mol Biol. Fani R. Gene duplication and gene loading. In: Microbial evolution: gene establishment, survival, and exchange.
Fani R, Fondi M. Origin and evolution of metabolic pathways. Phys Life Rev. The evolution of the histidine biosynthetic genes in prokaryotes: a common ancestor for the hisA and hisF genes.
Molecular evolution of the histidine biosynthetic pathway. The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case. The management of biochemical reactions with enzymes is an important part of cellular maintenance.
Enzymatic activity allows a cell to respond to changing environmental demands and regulate its metabolic pathways, both of which are essential to cell survival. Topic rooms within Cell Biology Close. No topic rooms are there. Or Browse Visually. Student Voices. Creature Cast. Simply Science. Green Screen. Green Science. Bio 2. The Success Code. Why Science Matters. The Beyond. Plant ChemCast. Postcards from the Universe. Brain Metrics. Mind Read. Eyes on Environment. Accumulating Glitches. Saltwater Science.
Microbe Matters. You have authorized LearnCasting of your reading list in Scitable. Types of Metabolic Pathways. Brent Cornell. Cell Introduction 2. Cell Structure 3. Membrane Structure 4. Membrane Transport 5. Origin of Cells 6. Cell Division 2: Molecular Biology 1. Metabolic Molecules 2. Water 3. Protein 5. Enzymes 6.
0コメント