Different organisms need to synthesize different kinds of complex molecules. Autotrophic organisms, such as plants, can use simple small molecules, such as carbon dioxide and water, to synthesize complex organic molecules, such as polysaccharides and protein. Heterotrophs needs more complex material sources, such as monosaccharides and amino acids, to produce corresponding complex molecules. According to different energy sources, organisms can also be divided into photoautotrophs and photoheterotrophs, and chemoautotrophs and chemoautotrophs obtained from inorganic oxidation process or energy. Plant cells (surrounded by purple cell walls) are full of chloroplasts (green), which is the "factory" of photosynthesis.
Photosynthesis is a process that uses sunlight, carbon dioxide (CO2) and water to synthesize sugars and release oxygen. This process uses ATP and NADPH produced by photosynthetic reaction center to convert CO2 into 3- phosphoglyceric acid, and continues to convert 3- phosphoglyceric acid into glucose needed by organisms, so this process is called carbon fixation. As part of Calvin-Benson cycle, carbon fixation is catalyzed by RuBisCO enzyme. Photosynthesis in plants can be divided into three types: C3 carbon fixation, C4 carbon fixation and CAM photosynthesis. The difference between these photosynthetic species is that carbon dioxide enters calvin cycle in different ways: C3 plants can directly fix carbon dioxide; C4 and CAM types first combine CO2 with other compounds, which is adapted to strong light and dry environment.
In photosynthetic prokaryotes, the mechanism of carbon fixation is only more different. For example, carbon dioxide can be fixed by Calvin-Benson cycle (trans-citric acid cycle) [or carboxylation of acetyl coenzyme A]. In addition, prokaryotic autotrophic bacteria can also fix CO2 through Calvin-Benson cycle, but use energy from inorganic compounds to drive the reaction. In the anabolism of sugar, simple organic acids can be converted into monosaccharides (such as glucose), and then the monosaccharides are polymerized together to form polysaccharides (such as starch). The process of producing glucose from compounds including pyruvate, lactic acid, glycerol, glyceric acid 3- phosphate and amino acids is called gluconeogenesis. Gluconeogenesis converts pyruvate into glucose -6- phosphate through a series of intermediates, many of which can be shared with glycolysis. However, gluconeogenesis is not a simple reverse reaction of glycolysis, and many steps are catalyzed by enzymes that do not work in glycolysis. In this way, the synthesis and decomposition of glucose can be regulated and controlled respectively, and these two pathways can be prevented from entering an ineffective cycle.
Although fat is a common way to store energy, in vertebrates such as humans, stored fatty acids cannot be converted into glucose by gluconeogenesis, because these organisms cannot convert acetyl-CoA into pyruvate (plants have necessary enzymes, but animals don't). Therefore, after long-term hunger, vertebrates need to use fatty acids instead of glucose in tissues to make ketone bodies, because tissues like the brain cannot metabolize fatty acids. In other organisms, such as plants and bacteria, due to glyoxylic acid cycle, the decarboxylation reaction in citric acid cycle can be skipped, and acetyl-CoA can be converted into oxaloacetic acid to produce glucose, thus solving this metabolic problem in vertebrates.
Polysaccharides and polysaccharides are synthesized by gradually adding monosaccharides. The process of adding monosaccharide is that the sugar group is transferred from the activated sugar-phosphate donor (such as glucouridine diphosphate) to the hydroxyl group as the acceptor (located on the extended polysaccharide chain). Because any hydroxyl group on the sugar ring can be used as an acceptor, the polysaccharide chain can be straight chain structure or contain multiple branches. These produced polysaccharides can have structural or metabolic functions themselves, and can also be transferred to lipids and protein under the action of oligosaccharide chain transferase (i.e. glycosylation).
Fatty acids, terpenoids and steroids
Schematic diagram of steroid metabolism pathway. Among them, isopentene pyrophosphate (IPP), dimethyl allyl pyrophosphate (DMAPP), geranium pyrophosphate (GPP) and squalene are the intermediates. Some intermediates were omitted. The product is lanosterol.
Fatty acid synthesis is the process of polymerization and reduction of acetyl coenzyme A. The acetyl chain on fatty acid extends through a reaction cycle, including the process of adding acetyl group, reducing it to ethanol, and continuing to reduce it to alkanes. Enzymes that play a role in fatty acid biosynthesis can be divided into two categories: in animals and fungi, all fatty acid synthesis reactions are completed by a single multifunctional enzyme-type I fatty acid synthase; In plant plastids and bacteria, there are many different enzymes that catalyze each reaction, which are collectively called type I fatty acid synthase.
Terpenes and isoprene compounds (including carotenoids) are a large family of lipids, which constitute the largest class of natural compounds in plants. These compounds are polymerized and modified with isoprene as a unit; Among them, isoprene is provided by reactive precursors isopentene pyrophosphate and diallyl pyrophosphate. [These two precursors can be synthesized by different methods. Animals and archaea produce these two compounds from acetyl-CoA by methylic acid pathway. Plants and bacteria use pyruvate and glyceraldehyde -3- phosphate as substrates, which are produced through non-methyl uric acid pathway. Another important reaction using these activated isoprene donors is steroid biosynthesis. Among them, isoprene units are linked together to form squalene, which is folded again and lanosterol is obtained through continuous cyclization initiated by protons. Lanosterol can be continuously converted into other steroids, such as cholesterol and ergosterol.
protein
The ability of biosynthesis of 20 basic amino acids varies from organism to organism. Most bacteria and plants can synthesize these 20 amino acids, while mammals can only synthesize 10 non-essential amino acids. Therefore, for mammals, including humans, the only way to obtain essential amino acids is to eat foods rich in these amino acids. All amino acids can be produced by the intermediate products of glycolysis, citric acid cycle or pentose phosphate cycle. Among them, the nitrogen required for the synthesis process is provided by glutamic acid and glutamine. Amino acid synthesis requires the formation of appropriate α -keto acids, and then amino acids are formed by transamination.
Amino acids are linked together by peptide bonds to further form protein. Each protein has its own unique amino acid sequence (also called primary structure). Just as more than 20 letters can be arranged and combined into tens of thousands of words, different amino acids can be connected to form a large number of protein species. Amino acids are activated by connecting to corresponding transport RNA(t RNA) molecules to form aminoacyl trna, and then they can be connected together. This aminoacyl -tRNA precursor is synthesized by ATP-dependent reaction (connecting trna with the correct amino acid), which is catalyzed by aminoacyl -tRNA synthetase. [Then, under the guidance of the sequence information in the messenger RNA, the amino acid correct aminoacyl -tRNA molecule can be bound to the corresponding position of the ribosome, and the amino acid can be connected to the extended protein chain under the action of the ribosome.
nucleotide
Nucleotides are synthesized from amino acids, carbon dioxide and formic acid. Because its synthetic pathway needs to consume a lot of metabolic energy, most organisms have effective nucleotide rescue systems. Purine is synthesized on the basis of nucleoside (that is, ribose attached to base). Adenine and guanine are derived from inosine monophosphate (inosine monophosphate), which is a precursor nucleoside molecule, and inosine monophosphate is synthesized from glycine, glutamine and glutamine atoms and formic acid groups transferred by coenzyme tetrahydrofolate. Pyrimidine is synthesized from the base orotate, which is converted from glutamine and glutamine.
Heterotypic biomass metabolism and redox metabolism
If all living things continue to ingest non-food substances without corresponding metabolic pathways, these substances will accumulate in cells and cause harm. These substances that exist in the body and may cause damage are called xenobiotics. Heterogeneous biomass includes synthetic drugs, natural poisons and antibiotics. Fortunately, they can be detoxified by a series of metabolic enzymes of alien biomass. In human body, cytochrome P450 oxidase, UDP- glucuronosyltransferase and glutathione S- transferase all belong to this kind of enzymes. The function of this enzyme system has three stages: firstly, the heterogeneous biomass is oxidized, then water-soluble groups are attached to the substance molecules, and finally the modified heterogeneous biomass containing water-soluble groups is transported out of the cell (in multicellular organisms, it can be further metabolized and excreted). In ecology, these reactions play an extremely important role in microbial degradation of pollutants and bioremediation of contaminated soil (especially oil pollution). Many of these microbial reactions also exist in multicellular organisms, but due to the diversity of microbial species, they can metabolize much more substances than multicellular organisms, and even degrade persistent organic pollutants including organochlorine.
Aerobic organisms also have the problem of oxidative stress Among them, reactive oxygen species (such as hydrogen peroxide) produced by oxidative phosphorylation and disulfide bond formation in protein folding need to be treated. [These oxidative active substances that can damage the body are eliminated by antioxidant metabolites (such as glutathione) and related enzymes (such as catalase and horseradish peroxidase).
Biothermodynamics
Biology must also obey the laws of thermodynamics (describing the transfer relationship between work and heat). The second law of thermodynamics points out that entropy always tends to increase in any closed system. Although the high complexity of biology seems to violate this law, biology is actually an open system, which can exchange material and energy with the surrounding environment; Therefore, the life system is not in a state of equilibrium, but a dissipative structure that maintains its high complexity and increases the entropy of the surrounding environment. [Metabolism in cells maintains its complexity by coupling the spontaneous process of catabolism with the involuntary process of anabolism. According to thermodynamics, metabolism is actually to maintain order by creating disorder.
regulatory mechanism
Because the external environment of the organism is constantly changing, it is necessary to accurately adjust the metabolic reaction to maintain the stability of the components in the cell, that is, the balance in the body. Metabolic regulation also enables organisms to feedback external signals and interact with the surrounding environment. Among them, two closely related concepts are very important for understanding the regulation mechanism of metabolic pathway: first, the regulation of an enzyme in metabolic pathway is how its enzyme activity increases or decreases according to signals; Secondly, the control function of this enzyme is the influence of its activity change on the total rate (pathway flux) of metabolic pathway. For example, the activity of an enzyme can change greatly (for example, it is highly regulated), but if these changes have little effect on the flux of its metabolic pathway, then the enzyme cannot control this pathway.
Metabolic regulation can be divided into multiple levels. In self-regulation, metabolic pathways can self-regulate in response to changes in the level of substrates or products; For example, the decrease of product quantity can cause the increase of channel flux, so that the product quantity can be compensated. This type of regulation includes allosteric regulation of various enzyme activities in the pathway. In multicellular organisms, cells react after receiving signals from other cells and change their metabolism, which belongs to external regulation. These signals are usually transmitted by soluble molecules ("messengers"), such as hormones and growth factors, which can specifically bind to specific receptor molecules on the cell surface. After binding to the receptor, the signal will be transmitted to the cell through the second messenger system, which usually contains phosphorylation of protein.
Glucose metabolism regulated by insulin is a well-studied example of external regulation. [The body synthesizes insulin to cope with the increase of blood sugar level. Insulin binds to the insulin receptor on the cell surface, and then activates a series of protein kinase cascade reactions, so that cells can absorb glucose and convert it into energy storage molecules, such as fatty acids and glycogen. Glycogen metabolism is controlled by phosphorylase and glycogen synthase. The former can degrade glycogen, while the latter can synthesize glycogen. These enzymes are mutually regulated: phosphorylation can inhibit the activity of glycogen synthase, but activate the activity of phosphorylase. Insulin can reduce the phosphorylation of protein phosphatase by activating protein phosphatase, thus synthesizing glycogen.
develop
Phylogenetic tree shows that all creatures from three biological domains have a common ancestor. Bacteria are blue, eukaryotes are red and archaea are green. The relative positions of some doors are also marked around the phylogenetic tree.
As mentioned above, the central pathways of metabolism, such as glycolysis and tricarboxylic acid cycle, exist in all organisms in the three domains and once existed in the "last common ancestor". The common ancestor cells are prokaryotes, probably methanogens, which metabolize amino acids, sugars and lipids extensively. The reason why these ancient metabolic pathways have not evolved further may be that the reactions in the pathways have been optimized solutions to specific metabolic problems and can achieve high efficiency with few steps. The first enzyme-based metabolic pathway (which may now be part of purine nucleotide metabolism) and the previous metabolic pathway are part of the original RNA world.
Researchers have proposed various models to describe how new metabolic pathways evolved: for example, adding new enzymes to a shorter original pathway, or replicating and then differentiating the whole pathway, and bringing existing enzymes and their complexes into new reaction pathways. It is not clear which of these evolutionary mechanisms is more important, but genome research shows that enzymes in the same pathway may have a common "ancestor", which indicates that many pathways use existing reaction steps to obtain new functions through gradual evolution. Another reasonable model comes from the research on the evolution of protein structure in metabolic network. The results suggest that the enzyme is universal, and the same enzyme can be used in different metabolic pathways to play a similar role. These utilization processes lead to evolution, in which enzymes are spliced in a manner similar to mosaic arrangement. The third possibility is that some parts of metabolism can exist in the form of "modules", which can be used in different ways to perform similar functions on different molecules.
While evolving new metabolic pathways, evolution may also lead to the reduction or loss of metabolic function. For example, some parasites lose metabolic processes that are not critical to survival, but obtain amino acids, nucleotides and sugars directly from the host. Similar degradation of metabolic capacity was observed in some endosymbionts.
Related research and analysis
Metabolic network of tricarboxylic acid cycle in Arabidopsis thaliana Enzymes and metabolites are represented by red squares, and their interactions are represented by black lines.
The classic research method of metabolism is reduction method, that is, studying a single metabolic pathway. Radiotracer is a very useful research method, which tracks the metabolic process by locating the radioactive labeled intermediates and products, so that metabolism can be studied at different levels of the whole organism, tissue or cell. Subsequently, the enzymes catalyzing these chemical reactions were purified and their kinetic properties and corresponding inhibitors were identified. Another research method is to identify small molecules related to metabolism in cells or tissues, all of which are called metabolomics. To sum up, these studies give the composition structure and function of a single metabolic pathway; However, these methods cannot be effectively applied to more complex systems, such as all metabolism in a complete cell.
Intracellular metabolic networks (including thousands of different enzymes) are extremely complex, as shown in the right figure (only the interaction between 43 protein and 40 metabolites is included in the figure). However, genome data can be used to construct a complete metabolic chemical reaction network and generate a more complete mathematical model to explain and predict various metabolic behaviors. In particular, integrating the data of metabolic pathways and metabolites obtained by classical research methods, as well as the data obtained by protein omics and DNA microarray research into these mathematical models can greatly improve these mathematical models. Using all these technologies, a human metabolic model is proposed, which will provide guidance for future drug and biochemical research.
One of the main technical applications of metabolic information is metabolic engineering. In metabolic engineering, organisms such as yeast, plants and bacteria are transformed into effective tools in biotechnology through genetic engineering, which are used to produce drugs, including antibiotics or industrial chemicals such as 1, 3- propanediol and shikimic acid. [[These transformations usually help to reduce energy consumption in product synthesis, increase output and reduce waste generation.