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1.
Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.  相似文献   

2.
The darwinian concept of "descent with modification" applies to metabolic pathways: pathways sharing similarities must have inherited them from an exclusive, hypothetical ancestral pathway. Comparative anatomy of biochemical pathways is performed using five criteria of homology. Primary homologies of "type I" were defined as several pathways sharing the same enzyme with high specificity for its substrate. Primary homologies of "type II" were defined as the sharing of similar enzymatic functions, cofactors, functional family, or recurrence of a set of reactions. Standard cladistic analysis is used to infer the evolutionary history of metabolic development and the relative ordering of biochemical reactions through time, from a single matrix integrating the whole basic universal metabolism. The cladogram shows that the earliest pathways to emerge are metabolism of amino acids of groups I and II (Asp, Asn, Glu, and Gln). The earliest enzymatic functions are mostly linked to amino acid catabolism: deamination, transamination, and decarboxylation. For some amino acids, catabolism and biosynthesis occur at the same time (Asp, Glu, Lys, and Met). Catabolism precedes anabolism for Asn, Gln, Arg, Trp, His, Tyr, and Phe, and anabolism precedes catabolism for Pro, Ala, Leu, Val, Ile, Cys, Gly, Ser, and Thr. The urea cycle evolves from arginine synthesis. Metabolism of fatty acids and sugars develops after the full development of metabolism of amino acids of groups I and II, and they are associated with the anabolism of amino acids of groups III and IV. Syntheses of aromatic amino acids are branched within sugar metabolism. The Krebs cycle occurs relatively late after the setting of metabolism of amino acids of groups I and II. One portion of the Krebs cycle has a catabolic origin, whereas the other portion has an anabolic origin in pathways of amino acids of groups III and IV. It is not possible to order glycolysis and gluconeogenesis with regard to the Krebs cycle, as they all belong to "period 6." Pentose-phosphate and Calvin cycles are later (periods 7 and 8, respectively). Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.  相似文献   

3.
V A Konyshev 《Genetika》1983,19(1):17-25
The correlations between genetic codes of amino acids and pathways of synthesis and catabolism of carbon backbone of amino acids are considered. Codes of amino acids which are synthesized from oxoacids of glycolysis, the Krebs cycle and glyoxalic cycle via transamination without any additional chemical reactions, are initiated with guanine (alanine, glutamic and aspartic acids, glycine). Codons of amino acids which are formed on the branches of glycolysis at the level of compounds with three carbon atoms, begin with uracil (phenylalanine, serine, leucine, tyrosine, cysteine, tryptophan). Codes of amino acids formed from aspartate begin with adenine (methionine, isoleucine, threonine, asparagine, lysine, serine), while those of the amino acids formed from the compounds with five carbon atoms (glutamic acid and phosphoribosyl pyrophosphate) begin with cytosine (arginine, proline, glutamine, histidine). The second letter of codons is linked to catabolic pathways of amino acids: most of amino acids entering glycolysis and the Krebs cycle through even-numbered carbon compounds, have adenine and uracil at the second position of codes (A-U type); most of amino acids entering the glycolysis and the Krebs cycle via odd-numbered carbon compounds, have codons with guanine and cytidine at the second position (G-C type). The usage of purine and pyrimidine as the third letter of weak codones in most of amino acids is linked to the enthropy of amino acid formation. A hypothesis claiming that the linear genetic code was assembled from the purine and pyrimidine derivatives which have acted as participants of primitive control of amino acid synthesis and catabolism, is suggested.  相似文献   

4.
Metabolic pathways exhibit structures resulting from an evolutionary process. Pathways have been inherited through time with modification, from the earliest periods of life. It is possible to compare the structure of pathways as done in comparative anatomy, i.e. for inferring ancestral pathways or parts of it (ancestral enzymatic functions), using standard phylogenetic reconstruction. Thus a phylogenetic tree of pathways provides a relative ordering of the rise of enzymatic functions. It even becomes possible to order the birth of each complete pathway in time. This particular "DNA-free" conceptual approach to evolutionary biochemistry is reviewed, gathering all the justifications given for it. Then, the method of assigning a given pathway to a time span of biochemical development is revisited. The previous method used an implicit "clock" of metabolic development that is difficult to justify. We develop a new clock-free approach, using functional biochemical arguments. Results of the two methods are not significantly different; our method is just more precise. This suggests that the clock assumed in the first method does not provoke any important artefact in describing the development of biochemical evolution. It is just unnecessary to postulate it. As a result, most of the amino acid metabolic pathways develop forwards, confirming former models of amino acid catabolism evolution, but not those for amino acid anabolism. The order of appearance of sectors of universal cellular metabolism is: (1) amino acid catabolism, (2) amino acid anabolism and closure of the urea cycle, (3) glycolysis and glycogenesis, (4) closure of the pentose-phosphate cycle, (5) closure of the Krebs cycle and fatty acids metabolism, (6) closure of the Calvin cycle.  相似文献   

5.
When radioactive polyamines (putrescine or spermidine) were incubated with mammalian cells in tissue culture, the radioactivity was incorporated into cellular proteins via two different metabolic pathways; one is metabolic labeling of an 18,000-dalton protein via hypusine formation, and the other is general protein synthesis employing radioactive amino acids derived from biodegradation of polyamines via GABA shunt and Krebs cycle. Aminoguanidine, a potent inhibitor of diamine oxidase, blocked the metabolic conversion of polyamines to amino acids but had no effect on the metabolic labeling of the 18,000-dalton protein. We have investigated these two polyamine-associated biochemical events in IMR-90 human diploid fibroblasts as a function of their population doubling level (PDL). We found that (1) the metabolic labeling of the 18,000-dalton protein was about two-fold greater in young cells (PDL = 22) than that in old cells (PDL = 48), and (2) the metabolic labeling of other cellular proteins, employing amino acids derived from putrescine via polyamine catabolic pathway, was more than six-fold greater in the old cells (PDL = 48) than in the young cells (PDL = 22). Since the rate of protein synthesis was about 1.4-fold higher in the young cells as compared to the old cells, our data indicated that the activity of catabolic conversion of putrescine (or spermidine) to amino acids in old IMR-90 cells was about eight-fold greater than that in young cells. This remarkable increase of polyamine catabolism and the slight decrease of metabolic labeling of the 18,000-dalton protein were also observed in cell strains derived from patients with premature aging disease.  相似文献   

6.
Enzymes control the course of biochemical reactions. The enzymes involved in bioenergetic processes play most important role in cell metabolism. One of them is 2-oxoglutarate dehydrogenase complex (OGDHC), the key regulatory enzyme of Krebs cycle. Krebs cycle integrates basic metabolic pathways of carbohydrates, fatty acids and amino acids during catabolic as well as anabolic reactions. Due to the key position of OGDHC in mitochondrial metabolism, its activity is controlled by many factors. Allosteric regulation by positive effectors (ADP, Pi, Ca2+, Mn2+) of the complex is very important. These effectors strongly enhances affinity of the first component of OGDHC to 2-oxoglutarate. Moreover there are negative effectors (ATP, NADH, succinyl-CoA) which affect all three enzymes of the complex. Regulation of biosynthesis of individual components of the complex by activation or inactivation of genes expression is very important for proper OGDHC activity too. Activity of OGDHC also depends on posttranslational modifications of its components. All of this control processes maintain OGDHC activity on adequate level and prevent the complex against its excessive action.  相似文献   

7.
A yeast glutamate auxotroph (glt1 ? 1), blocked in the tricarboxylic acid cycle at aconitase, is shown to possess catabolic pathways to glutamate from proline, arginine and glutamine, and grows on any of these amino acids in a minimal medium. This mutant does not, however, grow on these amino acids in a medium containing the full complement of common amino acids minus glutamate. The mechanism of this growth failure involves partial inhibition of the catabolic routes to glutamate by more than half the common amino acids. In the case of proline catabolism, this inhibition is localized principally at the enzyme Δ1-pyrroline-5-carboxylate: NAD(P)+ oxidoreductase by in vitro studies. Similar results with this enzyme prepared both from yeast and from beef kidney mitochondria suggest that the inhibition observed may be the basis of a regulatory mechanism of general significance.  相似文献   

8.
l-Leucine can be assimilated by bacteria when sugars or other preferential carbon sources in the habitat are depleted. The l-leucine catabolism is widely spread among bacteria and has been thoroughly studied. Its pathway is comprised by multiple reactions and converges with other catabolic routes, generating acetoacetate and acetyl-CoA as its final products. The initial three steps are conserved in most bacteria, constituting the first steps of the branched-chain amino acids catabolic pathway. The main product of these sequential reactions is the 3-methylcrotonyl-CoA metabolite, which undergoes further enzymatic steps towards the production of acetoacetate and acetyl-CoA. These, however, are not always the final products of l-leucine catabolism, as intermediates of the pathway can further synthesize fatty acids or feed other secondary metabolism pathways in order to produce diverse compounds which can exhibit biological activities. This alternative metabolism typically leads to the accumulation of products bearing industrial relevance, including volatile compounds used in the food industry, compounds with antimicrobial activity, production of biofuels and biopolymers. In anaerobic bacteria, the l-leucine catabolism may induce the accumulation of a variety of organic compounds acids, such as isovaleric, isocaproic, and 2-methylbutyric acids. In conclusion, the usage by bacterial species of l-leucine as an alternative carbon and nitrogen source may contribute to their environment adaptability and, more importantly, the diverse products that can be obtained from l-leucine metabolism may be represent a valuable source of compounds of biotechnological interest.  相似文献   

9.
A yeast glutamate auxotroph (glt1 − 1), blocked in the tricarboxylic acid cycle at aconitase, is shown to possess catabolic pathways to glutamate from proline, arginine and glutamine, and grows on any of these amino acids in a minimal medium. This mutant does not, however, grow on these amino acids in a medium containing the full complement of common amino acids minus glutamate. The mechanism of this growth failure involves partial inhibition of the catabolic routes to glutamate by more than half the common amino acids. In the case of proline catabolism, this inhibition is localized principally at the enzyme Δ1-pyrroline-5-carboxylate: NAD(P)+ oxidoreductase by in vitro studies. Similar results with this enzyme prepared both from yeast and from beef kidney mitochondria suggest that the inhibition observed may be the basis of a regulatory mechanism of general significance.  相似文献   

10.
An examination of cellular extracts ofLegionella pneumophila (Philadelphia 1 and Knoxville 1) was undertaken and key enzymes of the Embden-Meyerhof-Parnas (EMP) and pentose phosphate (PP) pathways, and the Krebs cycle were found. No enzymatic evidence of the ED pathway was obtained. In regard to carbon flow in the EMP pathway, the activities of fructose-1,6-biphosphatase (6–7.3 nmol/min/mg protein) and of phosphofructokinase (0.67–0.8 nmol/min/mg protein) suggested a gluconeogenic role. In further support of this direction, good activities were detected for phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase. While an energized membrane was required for glutamate uptake by whole cells, an energized mechanism for glucose uptake could not be demonstrated. The Krebs cycle was essentially complete and, despite high specific activities for isocitrate and malate dehydrogenases, whole cells failed to oxidize these substrates, suggesting a transport deficiency. The major carbon and energy sources serine and glutamate were catabolized vial-serine dehydratase and glutamate-aspartate transaminase, respectively. This study confirmed that amino acids are catabolized via the Krebs cycle and that sugars are synthesized by the gluconeogenic enzymes of the EMP pathway.  相似文献   

11.
Peptidases and amino acid catabolism in lactic acid bacteria   总被引:28,自引:0,他引:28  
The conversion of peptides to free amino acids and their subsequent utilization is a central metabolic activity in prokaryotes. At least 16 peptidases from lactic acid bacteria (LAB) have been characterized biochemically and/or genetically. Among LAB, the peptidase systems of Lactobacillus helveticus and Lactococcus lactis have been examined in greatest detail. While there are homologous enzymes common to both systems, significant differences exist in the peptidase complement of these organisms. The characterization of single and multiple peptidase mutants indicate that these strains generally exhibit reduced specific growth rates in milk compared to the parental strains. LAB can also catabolize amino acids produced by peptide hydrolysis. While the catabolism of amino acids such as Arg, Thr, and His is well understood, few other amino acid catabolic pathways from lactic acid bacteria have been characterized in significant detail. Increasing research attention is being directed toward elucidating these pathways as well as characterizing their physiological and industrial significance.  相似文献   

12.
The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into asingle-solution problem, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.  相似文献   

13.
The origin of the biosynthetic pathways for the branched-chain amino acids cannot be understood in terms of the backwards development of the present acetolactate pathway because it contains unstable intermediates. We propose that the first biosynthesis of the branched-chain amino acids was by the reductive carboxylation of short branched chain fatty acids giving keto acids which were then transaminated. Similar reaction sequences mediated by nonspecific enzymes would produce serine and threonine from the abundant prebiotic compounds glycolic and lactic acids. The aromatic amino acids may also have first been synthesized in this way, e.g. tryptophan from indole acetic acid. The next step would have been the biosynthesis of leucine from -ketoisovaleric acid. The acetolactate pathway developed subsequently. The first version of the Krebs cycle, which was used for amino acid biosynthesis, would have been assembled by making use of the reductive carboxylation and leucine biosynthesis enzymes, and completed with the development of a single new enzyme, succinate dehydrogenase. This evolutionary scheme suggests that there may be limitations to inferring the origins of metabolism by a simple back extrapolation of current pathways.  相似文献   

14.
The functioning of the biosynthetic pathways of the amino acids alanine, glycine, aspartic acid, glutamic acid and tyrosine, and of nucleosides in the photosynthetic bacterium Chlorobium thiosulfatophilum during heterotrophic growth on 13CO2 and unlabelled acetate was investigated using 13C-NMR as the method for determination of the labelling patterns of the separated substances. On the basis of the analysis of the multiplet structure of the spectra of the tightly-coupled systems, the conclusion was drawn that the Calvin cycle does not function in the experimental conditions used. The labelling pattern of the glutamic acid indicated that about 30% of the amino acid molecules were synthesized through the reactions of the reductive carboxylic acid cycle, the remaining 70% being derived from oxaloacetate and exogenous acetate through the reactions of the Krebs cycle. Labelling patterns of the nucleosides were in agreement with their known biosynthetic pathways.  相似文献   

15.
Between the different types of Acyl-CoA dehydrogenases (ACADs), those specific for branched chain acyl-CoA derivatives are involved in the catabolism of amino acids. In mammals, isovaleryl-CoA dehydrogenase (IVD), an enzyme of the leucine catabolic pathway, is a mitochondrial protein, as other acyl-CoA dehydrogenases involved in fatty acid beta-oxidation. In plants, fatty acid beta-oxidation takes place mainly in peroxisomes, and the cellular location of the enzymes involved in the catabolism of branched-chain amino acids had not been definitely assigned. Here, we describe that highly purified potato mitochondria have important IVD activity. The enzyme was partially purified and cDNAs from two different genes were obtained. The partially purified enzyme has enzymatic constant values with respect to isovaleryl-CoA comparable to those of the mammalian enzyme. It is not active towards straight-chain acyl-CoA substrates tested, but significant activity was also found with isobutyryl-CoA, implying an additional role of the enzyme in the catabolism of valine. The present study confirms recent reports that in plants IVD activity resides in mitochondria and opens the way to a more detailed study of amino-acid catabolism in plant development.  相似文献   

16.
The capacity of Escherichia coli to adapt its catabolism to prevailing redox conditions resides mainly in three catabolic branch points involving (i) pyruvate formate-lyase (PFL) and the pyruvate dehydrogenase complex (PDHc), (ii) the exclusively fermentative enzymes and those of the Krebs cycle, and (iii) the alternative terminal cytochrome bd and cytochrome bo oxidases. A quantitative analysis of the relative catabolic fluxes through these pathways is presented for steady-state glucose-limited chemostat cultures with controlled oxygen availability ranging from full aerobiosis to complete anaerobiosis. Remarkably, PFL contributed significantly to the catabolic flux under microaerobic conditions and was found to be active simultaneously with PDHc and cytochrome bd oxidase-dependent respiration. The synthesis of PFL and cytochrome bd oxidase was found to be maximal in the lower microaerobic range but not in a delta ArcA mutant, and we conclude that the Arc system is more active with respect to regulation of these two positively regulated operons during microaerobiosis than during anaerobiosis.  相似文献   

17.
The catabolic and energy metabolism capacities during spotted wolffish (Anarhichas minor) embryogenesis were investigated. We assessed the embryo's ability to catabolize proteins (trypsin-like proteases) and lipids (triglyceride lipase) and examined the development of metabolic capacities using enzymatic assays: ability to use carbohydrates (pyruvate kinase), amino acids (aspartate aminotransferase) and fatty acids (hydroxyacyl-CoA dehydrogenase) for energy production, and aerobic (citrate synthase) and anaerobic (lactate dehydrogenase) energy production. Functional enzymatic systems were detected from the eyed stage (350 degree-days), except for fatty acids, which was detected from 540 degree-days. To compare the development of 1) aerobic and anaerobic pathways and 2) the capacity to mobilize the different energy substrates, enzymatic ratios were calculated. Anaerobic capacity appeared to increase at a significantly higher rate than the aerobic capacity. Ratios revealing the relative capacity to use specific energy substrates showed a significantly slower increase during development in the capacity to use carbohydrates than amino acids and fatty acids. The end of embryogenesis was characterized by a significant decrease in the use of carbohydrates for aerobic energy production but an increasing capacity to use amino acids. Egg survival as affected by the variability in metabolic parameters is discussed.  相似文献   

18.
The present study aimed to explore the lactation-induced changes in hepatic gene expression in sows (Sus scrofa) during lactation. Using a porcine whole-genome microarray a total of 632 differentially expressed genes in the liver of lactating compared to non-lactating sows could be identified. Enrichment analysis revealed that the differentially expressed genes were mainly involved in fatty acid metabolism, pyruvate metabolism, glutathione metabolism, glycine, serine and threonine metabolism, citrate cycle, glycerophospholipid metabolism, PPAR signaling, and focal adhesion. The most striking observation with respect to intermediary metabolism was that genes involved in fatty acid catabolism, the catabolism of gluconeogenic amino acids, the citrate cycle and the respiratory chain were up-regulated in the liver of sows during lactation. With respect to immune response, it could be demonstrated that genes encoding acute phase proteins and genes involved in tissue repair were up-regulated and genes encoding adhesion molecules were down-regulated in the liver of sows during lactation. The results indicate that energy-generating pathways and pathways involved in the delivery of gluconeogenic substrates are induced in sow liver during lactation. The alterations of expression of genes encoding proteins involved in immune response suggest that lactation in sows may cause an adaptive immune response that possibly counteracts hepatic inflammation.  相似文献   

19.
BCAAs (branched-chain amino acids) are indispensable (essential) amino acids that are required for body protein synthesis. Indispensable amino acids cannot be synthesized by the body and must be acquired from the diet. The BCAA leucine provides hormone-like signals to tissues such as skeletal muscle, indicating overall nutrient sufficiency. BCAA metabolism provides an important transport system to move nitrogen throughout the body for the synthesis of dispensable (non-essential) amino acids, including the neurotransmitter glutamate in the central nervous system. BCAA metabolism is tightly regulated to maintain levels high enough to support these important functions, but at the same time excesses are prevented via stimulation of irreversible disposal pathways. It is well known from inborn errors of BCAA metabolism that dysregulation of the BCAA catabolic pathways that leads to excess BCAAs and their alpha-keto acid metabolites results in neural dysfunction. In this issue of Biochemical Journal, Joshi and colleagues have disrupted the murine BDK (branched-chain alpha-keto acid dehydrogenase kinase) gene. This enzyme serves as the brake on BCAA catabolism. The impaired growth and neurological abnormalities observed in this animal show conclusively the importance of tight regulation of indispensable amino acid metabolism.  相似文献   

20.
Glycine and serine are two interconvertible amino acids that play an important role in C1 metabolism. Using 13C NMR and various 13C-labelled substrates, we studied the catabolism of each of these amino acids in non-photosynthetic sycamore cambial cells. On one hand, we observed a rapid glycine catabolism that involved glycine oxidation by the mitochondrial glycine decarboxylase (GDC) system. The methylenetetra- hydrofolate (CH2-THF) produced during this reaction did not equilibrate with the overall CH2-THF pool, but was almost totally recycled by the mitochondrial serine hydroxymethyltransferase (SHMT) for the synthesis of one serine from a second molecule of glycine. Glycine, in contrast to serine, was a poor source of C1 units for the synthesis of methionine. On the other hand, catabolism of serine was about three times lower than catabolism of glycine. Part of this catabolism presumably involved the glycolytic pathway. However, the largest part (about two-thirds) involved serine-to-glycine conversion by cytosolic SHMT, then glycine oxidation by GDC. The availability of cytosolic THF for the initial SHMT reaction is possibly the limiting factor of this catabolic pathway. These data support the view that serine catabolism in plants is essentially connected to C1 metabolism. The glycine formed during this process is rapidly oxidized by the mitochondrial GDC-SHMT enzymatic system, which is therefore required in all plant tissues.  相似文献   

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