Wuxing Theory is an Ideal Mode for Discovering the Interrelationships Between the Energy Metabolism and Stem Cell Proliferation & Differentiation in Our Body

Xio Dngsheng (肖党生), Yng Jiezun (杨介钻), Fng Hui (方 辉)

a. VIP Ward, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China

b. First Affiliated Hospital, College of Medicine, Zhejiang University, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China

c. Department of Internal Medicine, First Affiliated Hospital,College of Medicine, Zhejiang University, Hangzhou 310000,China

ABSTRACT Yinyang theory and Wuxing theory are the core part in Traditional Chinese Medicine. On the principles of these theories, we definite the energy metabolism and stem cell proliferation & differentiation (SCPD) as yang and yin respectively. There are five factors which can influence the energy metabolism and SCPD: nutrition, oxygen, energy,end metabolic products and stem cell. These five factors have their metabolic pathways in our body. On the principle of wuxing theory, supply of nutrition should be regarded as earthTCM, supply of oxygen as metalTCM, releasing and utilization of energy as fireTCM, releasing of end metabolic products as waterTCM, and SCPD as woodTCM. The interrelationship between the five pathways can be described on the principle of wuxing theory. In all, both yinyang theory and wuxing theory are the just model to discover the mysteries of life.

KEYWORDS: Yinyang; Wuxing; TCM; Energy metabolism; Stem cell

Reductionism plays an important role for us to discover the mysteries of life[1,2]. On the principles of reductionism, we can give detailed researches on tissues,organs and cells in our body as well as proteins or pathways in cells. Now, we had known that there are many organs in our body which are made of billions of cells and there are thousands of proteins or a variety of biomolecules in a cell. Still there are many puzzles wandering in our mind: why and how so many biomolecules, proteins are organized in cells and so many cells are organized in our body? How and why does a cell or individual respond to different stimuli? What is living force in our body even in a cell and how does it work? The list of such puzzles still goes on. Generations of researchers are fascinated with such puzzles and do their best to find out answers. Perhaps,Traditional Chinese Medicine (TCM) may take some new insights about such puzzles.

TCM, with a unique theory which is different from modern medicine, is characterized by its eyesight of the human body as a whole system. Yinyang theory and wuxing theory are the core parts of TCM. One of directions for the modernization of TCM is to give exact medical interpretation of these core concepts[3-6]. In past,we had coined the definitions of yinyang and wuxing in a cell. With these definitions, we can conclude that there are two core undividable pathways in cell: energy metabolism[7], which should be regarded as yang and gene expression which should be regarded as yin. Basing on the two pathways, all metabolisms can be simplified as the oxidation of energy agents while wuxing theory is a just model to interpret the interrelationships among these factors which play the direct effects on the oxidation of energy agents[8]. In our body, energy metabolism and stem cell proliferation & differentiation(SCPD) are also the two essential pathways which can be regarded as yang and yin respectively while all metabolisms can also be abstracted as oxidation of nutrition[9]. Still there are these five factors in our body which play their effects on the oxidation of energy agents and the interrelationships can also be described on the principles of the wuxing theory.

Figure 1. The energy metabolism in our body

THE ESSENTIAL PATHWAYS IN OUR BODY

In our body, energy metabolism and SCPD are the essential pathways. Energy metabolism is the oxidation of nutrition which can be divided into two steps. The first step is that nutrition is decomposed into energy agents such as monosaccharides, amino acids, fatty acids.The second step is that these energy agents, after being absorbed, will be oxidized into end metabolic products such as water, carbon dioxide, urea, etc. In both steps,chemical energy will be transformed into heat energy which will be utilized or released.

In our body, the oxidation of energy agents only occurred in cells and these cells will go to die after finishing their function[10]. At this time, stem cells will migrate from bone marrow to local tissue for proliferation& differentiation so as to take the place of the dead cells[10-12]. This is another essential pathway in our body:stem cell proliferation & differentiation.

Figure 2. The SCPD in human body

Now, we can conclude that energy agents(monosaccharides, amino acids and fatty acids), the substrates for all metabolisms in body, had two essential pathways in our body. Firstly, after being absorbed,energy agents will be oxidized into end metabolic products which will be discharged. This way is the same as the oxidation of energy agents and should be named as short metabolic pathways. Secondly, the absorbed energy agents will enter stem cells for building the structures of the cell and stimulate these cells to produce somatic cells. After somatic cells go to die, energy agents will be released from the decomposition of biomacromolecules and then enter energy metabolism for oxidation. This pathway, which is the combination of SCPD and energy metabolism with SCPD being first and energy metabolism being second, should be named as long pathways.With the short metabolic pathways and long metabolic pathway, all metabolisms in our body can be abstracted into a metabolic circle. All of organs, tissues, cells,proteins and biomolecular are organized for operation of this metabolic circle.

However, there are many metabolic bypasses connecting energy metabolism and SCPD and we should not deny that the oxidation of the energy agents is the core pathway in our body while the metabolic circle only presents a framework of this oxidation. A new question is how many factors can play their influences on the oxidation in our body? Just like those in cell, there are five factors which play direct effects on the oxidation of energy agents.The five factors is nutrition, oxygen, SCPD, releasing of energy, excretion of metabolic end products while every factor has its pathway and can influence the other. The relationships between of the five factors can be described on the principles of wuxing theory.

THE FIVE PATHWAYS IN OUR BODY.

In TCM, "retaining", "reverse-retaining","promoting" and "reverse-promoting" are the essential concepts to explain the relationships between five factors on the principles of wuxing theory. We had been insisting that wuxing should be translated as five pathways instead of five elements while the five factors were the core agents for every pathway respectively. In cell, energy agents,oxygen, genes, heat energy and end products can play their effects on the oxidation of energy agents. Every factor has its metabolic pathway respectively while a variety of molecules, proteins and organelles are organized for the operation of every pathway. Taking oxygen as an example,although oxygen plays its oxidation in mitochondria, many molecular, protein and nucleic acid are organized for this pathways and oxygen plays the dominant role. The same phenomenon can also appear in other factors.

Figure 3. The five pathways in cell

Same as those in cell, all metabolisms in our body can also be simplified as the oxidation of nutrition while the foods, oxygen, heat energy, end products and stem cell will play their effects on the oxidation. Every factor has its pathway and a variety of organs, tissues and cells are organized for serving these pathways. On the principles of wuxing theory, foods, oxygen, heat energy,end products and stem cell should be regarded as earthTCM,metalTCM, fireTCM, waterTCMand woodTCM, respectively while the wuxing theory is the just model for explaining the interrelationships between these factors.

The metabolic pathways of nutrition: earthTCM

Figure 4. The five pathways in our body

Our body can get the energy agents only from nutrition or foods. After being taken, foods will be digested into energy agents, which will be absorbed and stored in our body. All of digestive organs attend the digestion of nutrition and the absorbing of energy agents.After being absorbed, these energy agents will be stored as fat or glycogen in adipose tissue, muscle and liver. This is the essential metabolic pathway of nutrition while the supply and storages of energy agents should be regarded as earthTCMjust like that in cells.

We had pointed that in cell, proteins are also the pattern for the storage of energy agents, especially for the storage of amino acids. In cell, the storages of energy agents as proteins should be regarded as earthTCMreverseretaining woodTCM. In our body, energy agents can also be used for synthesis of proteins which will take the place of inactivated proteins or build the structure of cells. However, in the stem cells, synthesis of proteins is beneficial for proliferation & differentiation of stem cell.So, we can say that the supply of nutrition will stimulates the SCPD, which should be regarded as earthTCMreverseretaining woodTCM.

In our body, the next step for the absorbed energy agents is to be oxidized into end products which should be regarded as earthTCMpromoting metalTCM.

Nearly all energy agents are hydrosoluble and they must be dissolved in water for their metabolisms.Therefore, the supply of energy agents in our body may take the prevention against the discharge of water, which should be regarded as earthTCMretaining waterTCM.

Not all nutrition can be accepted by us and not all energy agents will be absorbed by our body. By neuroendocrine system, our body will take the needed energy agents and distribute them to all cells for metabolism which should be regard as fireTCMpromoting earthTCM.

Oxidation: metalTCM

Oxygen can not be stored in our body and we get oxygen only by respiratory movement of lung. After being inhaled, oxygen will be transported to all cells to oxidize the energy agents. This is aerobic oxidation and circulatory system attends this process. There are some anaerobic oxidations in our body, such as decompositions of dead cell, proteins and other organic molecules. In our body, the aerobic oxidation is an irreversible reaction so as to be beneficial for the anaerobic oxidation which will afford substrates for the aerobic oxidation. Both aerobic oxidation and anaerobic oxidation are the essential metabolic pathways in our body which should be regarded as metalTCM.

Both in cell and in our body, oxygen can oxidize all energy agents into end products, which should be regarded as metalTCMreverse-promoting earthTCM. During the oxidization, the production of end products should be regarded as metalTCMpromoting waterTCM. The water is the most important end products. At the same time, a lot of energy will be released which should be regarded as metalTCMreverse-retaining fireTCM.

In cell, the decomposition of proteins should be regarded as metalTCMretaining woodTCM. In stem cell, the decomposition of proteins will play negative effect on its proliferation & differentiation, which should be regarded as metalTCMretaining woodTCMin our body. On the other hand,all dead cells will be decomposed into energy agents which will be oxidized into end products. This process should also be regarded as metalTCMretaining woodTCM.

The releasing of end metabolic products: waterTCM

Water, carbon dioxide, urea, etc. are the end metabolic products in our body which will be excreted as sweet, urine or breathed out by lung. This is the pathway for the releasing of end metabolic products. Water is an important end product for as solvents, water can take other end products such as carbon dioxide, urea, out of our body.Furthermore, the excretion of water will take much energy,which should be regarded as waterTCMretaining fireTCM.As an end product, discharging of water will be beneficial for undergoing of oxidation, which should be regarded as waterTCMreverse-promoting metalTCM. As a solvent, water can solves all energy agents and take advantage for the absorbing of this energy agents, which should be regarded as waterTCMreverse-retaining earthTCM.

In cell, DNA is regarded as kidney essence and classified as waterTCM. DNA is double stranded molecule and hydrogen bonds play the important role to maintain the structure of DNA. Water can destroy the hydrogen bonds so that double stranded DNA will be unwound and replication or transcription of genes will be initiated. The syntheses of proteins, DNA, RNA are the key factors for the division and differentiation of stem cells. The condensation reaction of amino acids, mono ribonucleic acids, mononuclear deoxynucleic acids, are the key steps for the synthesis of proteins while the water is one of products of these reaction. In other word, the excretion of water will be beneficial for the synthesis of these biomolecules so as to promote the SCPD, which should be regarded as waterTCMpromoting woodTCM. Factually, the releasing of water is the double-edged sword for SCPD for the releasing of water will help the DNA to be in the closed state which is disadvantageous for replication and transcription so that the stem cell will keep in silence. For this reason, the stem cell should be regarded as kidney essence in our body.

Releasing and utilization of energy: fireTCM

There are two detectable models for our body to releasing the energy carried by energy agents. One is the heat energy. Heat energy is the molecular irregular thermal motion. The general idea is that radiation, conduction,convection and sweating are the main method for our body to release heat energy. On the principles of thermodynamics(E=1/2mv2), water is the just molecule to carry the heat energy. So, the heat can drive the water off our body, which should be regarded as fireTCMreverse-retaining waterTCM.Factually, heat energy can also drive other end products off our body, which should also be regarded as fireTCMreverseretaining waterTCM. Another is the mechanic energy which should be regarded as the utilization of the energy carried by energy agents. Writing, speaking, running, breathing,and heart beating are the mechanic energy, during which the energy carried by energy agents are transformed into mechanic energy. On the principles of physics, mechanic energy will be transformed into heat energy ultimately for driving the water off our body.

It should be admitted that mechanic motion is the outward functions of our body or organs. Nearly all mechanic motions of our body or organs are controlled by neuroendocrine system. By action potential, neuron cells sent the regulation signal from brain to effectors including muscles. By releasing neurotransmitters, hormones or cytokines, neuroendocrine cells regulate the metabolism of our body including mechanic motions of our body or organs. Action potential is the transformation from chemical energy to electric energy. Neurotransmitters,hormones or cytokine should be regarded as carriers of chemical energy just like energy agents while synthesis and releasing of these biomolecules should also be regarded as the transformation from chemical energy to another one. So, action potential and chemical energy released by neuroendocrine system should also be regarded as the utilization of energy released by the oxidation of energy agents. In the other word, with the neuroendocrine system,our body uses a little energy to regulate all metabolisms in our body including the mechanic motion of organs and body as well as the releasing of heat energy. By observing the mechanic motion of organs or/and our body, we can conclude the collective action of neuroendocrine system.

Now, our conclusion is that the neuroendocrine system should be regarded as fireTCM, which regulates all metabolisms in our body. On the principle of wuxing theory, neuroendocrine system regulating the excretion of water should be regarded as fireTCMreverse-retaining waterTCM. Neuroendocrine system regulating the uptake,digestion and absorbing of nutrition should be regarded as fireTCMpromoting earthTCM. Neuroendocrine system regulating the proliferation & differentiation of stem cells should be regarded as fireTCMreverse-promoting woodTCM.Neuroendocrine system regulating the uptake of oxygen should be regarded as fireTCMretaining metalTCM.

SCPD: woodTCM

It should not be denied that by SCPD, a seed will grow into a tree which will afford a lot of wood. For us, by SCPD, a fertilized egg will grow into mature individuals. As for a multicellular individual, SCPD is the key difference from the inanimate entity. SCPD is the another core pathway in our body, which should be regarded as woodTCM[13]. When stem cells go into proliferation & differentiation, they will absorb energy agents for the constructing their structures which should be regarded as woodTCMretaining earthTCM. Somatic cells attend energy metabolism and play their functions,which should be regarded as woodTCMpromoting fireTCM.When stem cells go into proliferation & differentiation,anabolism is stronger than catabolism so that the oxidation is partly inhabited, which be regarded as woodTCMreverse–retaining metalTCMwhile the somatic cell going to death and being decomposed into energy agents should be regarded as metalTCMretaining woodTCM.

In our body, stem cell should be classified as kidney essence for they are stored in marrow. When stem cells are activated, they will go into proliferation& differentiation, which should be regarded as woodTCMreverse-promoting waterTCM. For SCPD, the synthesis of DNA, RNA, and protein are necessary while water is the by-product. This means that SCPD will be beneficial for the product of water, which should also be regarded as woodTCMreverse-promoting waterTCM.

We had pointed out that organic molecules should be regarded as carriers of chemical energy. On this ideal, we can get following conclusions. Firstly, cell is composed of a variety of organic molecules, so cell should also be regarded as a carrier of chemical energy. Secondly, cell division is the process that a mother cell produces two daughter cells and we can also say cell division is the process that a mother cell release chemical energy as a daughter cell, which should be regarded as woodTCMpromoting fireTCM.

SUMMARY

Wuxing theory will take many novel understandings on the living entity with the energy metabolism as the core pathway. Now, we abstracted our understanding on wuxing theory in following figure.

In fact, both in our body and in a cell, the five pathways are undividable. Any function of our body,organs and tissues are the collective behaviors of the five pathways with one pathway playing the dominant role. Taking the walking and speaking as the examples,both behaviors are the transformations from chemical energy to mechanic energy. During these behaviors,neuroendocrine system (fireTCM) plays the dominant role for this the system regulates the motion of muscles.However, our body or local tissues and organs must get energy agents from nutrition or food (earthTCM) and oxygen (metalTCM) will oxidize the energy agents into end products(waterTCM) which will be released. At the same time, stem cell(woodTCM) will product new somatic cells to replace the dead ones. In case that any pathway was out of order, walking or speaking will be abnormal.

"Retaining", "reverse-retaining", "promoting"and "reverse-promoting" are the words to describe therelationships between the five pathways, but they are not the just translation. Factually, one pathway may take advantage or disadvantage to another pathway at different condition. For example, the relationship between supply of oxygen and SCPD is described as metalTCMretaining woodTCMwhich does not imply that oxygen will only take the disadvantage to the SCPD. Oxygen is cytotoxic to cells and can kill all cells. However, at the case that oxygen can oxidize the dead cells into end metabolic products, stem cell will get the place for the producing news somatic cells, which implies that oxygen take the advantage for SCPD. On the contrary, at the case that oxygen takes the cytotoxicity to stem cells, stem cells will go to die which is disadvantageous for SCPD. The same interrelationships always appear between other pathways and we need some syndromes or parameters to distinguish the advantage or disadvantage, which is another fascinating field in the modernization of TCM.

Table 1. The relationship between wuxing theory and the five pathways in cell and in body

In all, on the principle of yinyang theory and wuxing theory, a novel mode about our body is presented.In this model, energy metabolism and SCPD play the dominant role in all behaviors of our body or organs.Nutrition, oxygen, end metabolic products, SCPD, and energy releasing, which have their pathways in our body,will influence the energy metabolism and SCPD. When the five pathways are in normal, our body will be in health or in a good state. At the case that any pathway is out of order, our body will feel unsatisfied or get some diseases. Perhaps, rectifying the abnormality of one or more pathways is the general therapy to the diseases.