Sabtu, 14 Februari 2009
Sabtu, 07 Februari 2009
The Urea Cycle
The Urea Cycle
Earlier it was noted that kidney glutaminase was responsible for converting excess glutamine from the liver to urine ammonium. However, about 80% of the excreted nitrogen is in the form of urea which is also largely made in the liver, in a series of reactions that are distributed between the mitochondrial matrix and the cytosol. The series of reactions that form urea is known as the Urea Cycle or the Krebs-Henseleit Cycle.
The essential features of the urea cycle reactions and their metabolic regulation are as follows: Arginine from the diet or from protein breakdown is cleaved by the cytosolic enzyme arginase, generating urea and ornithine. In subsequent reactions of the urea cycle a new urea residue is built on the ornithine, regenerating arginine and perpetuating the cycle.
Ornithine arising in the cytosol is transported to the mitochondrial matrix, where ornithine transcabamoylase catalyzes the condensation of ornithine with carbamoyl phosphate, producing citrulline. The energy for the reaction is provided by the high-energy anhydride of carbamoyl phosphate. The product, citrulline, is then transported to the cytosol, where the remaining reactions of the cycle take place.
The synthesis of citrulline requires a prior activation of carbon and nitrogen as carbamoyl phosphate (CP). The activation step requires 2 equivalents of ATP and the mitochondrial matrix enzyme carbamoyl phosphate synthetase-I (CPS-I). There are two CP synthetases: a mitochondrial enzyme, CPS-I, which forms CP destined for inclusion in the urea cycle, and a cytosolic CP synthatase (CPS-II), which is involved in pyrimidine nucleotide biosynthesis. CPS-I is positively regulated by the allosteric effector N-acetyl-glutamate, while the cytosolic enzyme is acetylglutamate independent.
In a 2-step reaction, catalyzed by cytosolic argininosuccinate synthetase, citrulline and aspartate are condensed to form argininosuccinate. The reaction involves the addition of AMP (from ATP) to the amido carbonyl of citrulline, forming an activated intermediate on the enzyme surface (AMP-citrulline), and the subsequent addition of aspartate to form argininosuccinate.
Arginine and fumarate are produced from argininosuccinate by the cytosolic enzyme argininosuccinate lyase (also called argininosuccinase). In the final step of the cycle arginase cleaves urea from aspartate, regenerating cytosolic ornithine, which can be transported to the mitochondrial matrix for another round of urea synthesis. The fumarate, generated via the action of arginiosuccinate lyase, is reconverted to aspartate for use in the argininosuccinate synthetase reaction. This occurs through the actions of cytosolic versions of the TCA cycle enzymes, fumarase (which yields malate) and malate dehydrogenase (which yields oxaloacetate). The oxaloacetate is then transaminated to aspartate by AST.
Beginning and ending with ornithine, the reactions of the cycle consumes 3 equivalents of ATP and a total of 4 high-energy nucleotide phosphates. Urea is the only new compound generated by the cycle; all other intermediates and reactants are recycled. The energy consumed in the production of urea is more than recovered by the release of energy formed during the synthesis of the urea cycle intermediates. Ammonia released during the glutamate dehydrogenase reaction is coupled to the formation of NADH. In addition, when fumarate is converted back to aspartate, the malate dehydrogenase reaction used to convert malate to oxaloacetate generates a mole of NADH. These two moles of NADH, thus, are oxidized in the mitochondria yielding 6 moles of ATP.
The Glutamine Synthetase Reaction
The Glutamine Synthetase Reaction
The glutamine synthetase reaction is also important in several respects. First it produces glutamine, one of the 20 major amino acids. Second, in animals, glutamine is the major amino acid found in the circulatory system. Its role there is to carry ammonia to and from various tissues but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolyzed by the enzyme glutaminase (reaction below); this process regenerates glutamate and free ammonium ion, which is excreted in the urine.
Note that, in this function, ammonia arising in peripheral tissue is carried in a non-ionizable form which has none of the neurotoxic or alkalosis-generating properties of free ammonia.
Liver contains both glutamine synthetase and glutaminase but the enzymes are localized in different cellular segments. This ensures that the liver is neither a net producer nor consumer of glutamine. The differences in cellular location of these two enzymes allows the liver to scavenge ammonia that has not been incorporated into urea. The enzymes of the urea cycle are located in the same cells as those that contain glutaminase. The result of the differential distribution of these two hepatic enzymes makes it possible to control ammonia incorporation into either urea or glutamine, the latter leads to excretion of ammonia by the kidney.
When acidosis occurs the body will divert more glutamine from the liver to the kidney. This allows for the conservation of bicarbonate ion since the incorporation of ammonia into urea requires bicarbonate (see below). When glutamine enters the kidney, glutaminase releases one mole of ammonia generating glutamate and then glutamate dehydrogenase releases another mole of ammonia generating α-KG. The ammonia will ionizes to ammonium ion (NH4+) which is excreted. The net effect is a reduction in the concentration of hydrogen ion, [H+], and thus an increase in the pH (see also Kidneys and Acid-Base Balance).
The Glutamate Dehydrogenase Reaction
The reaction catalyzed by glutamate dehydrogenase is:
The glutamine synthetase reaction is also important in several respects. First it produces glutamine, one of the 20 major amino acids. Second, in animals, glutamine is the major amino acid found in the circulatory system. Its role there is to carry ammonia to and from various tissues but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolyzed by the enzyme glutaminase (reaction below); this process regenerates glutamate and free ammonium ion, which is excreted in the urine.
Note that, in this function, ammonia arising in peripheral tissue is carried in a non-ionizable form which has none of the neurotoxic or alkalosis-generating properties of free ammonia.
Liver contains both glutamine synthetase and glutaminase but the enzymes are localized in different cellular segments. This ensures that the liver is neither a net producer nor consumer of glutamine. The differences in cellular location of these two enzymes allows the liver to scavenge ammonia that has not been incorporated into urea. The enzymes of the urea cycle are located in the same cells as those that contain glutaminase. The result of the differential distribution of these two hepatic enzymes makes it possible to control ammonia incorporation into either urea or glutamine, the latter leads to excretion of ammonia by the kidney.
When acidosis occurs the body will divert more glutamine from the liver to the kidney. This allows for the conservation of bicarbonate ion since the incorporation of ammonia into urea requires bicarbonate (see below). When glutamine enters the kidney, glutaminase releases one mole of ammonia generating glutamate and then glutamate dehydrogenase releases another mole of ammonia generating α-KG. The ammonia will ionizes to ammonium ion (NH4+) which is excreted. The net effect is a reduction in the concentration of hydrogen ion, [H+], and thus an increase in the pH (see also Kidneys and Acid-Base Balance).
Kamis, 05 Februari 2009
POWERS OF THE MIND
POWERS OF THE MIND
All over the world there has been the belief in the supernatural through the ages. All of us have heard of extraordinary happenings, and many of us have had some personal experience of them. I would rather introduce the subject by telling you certain facts, which have come within my own experience. I once heard of a man who, if anyone went to him with questions in his mind, would answer them immediately; and I was also informed that he foretold events. I was curious, and went to see him with a few fr iends. We each had something in our minds to ask, and, to avoid mistakes, we wrote down our questions and put them in our pockets. As soon as the man saw one of us, he repeated our questions and gave answers to them. Then he wrote something on paper, whi ch he folded up, asked me to sign on the back, and said, 'Don't look at it; put it in your pocket, and keep it there till I ask for it again'. And so on to each of us. He next told us about some events that would happen to us in the future. Then he said, 'Now, think of a word or sentence, from any language you like.' I thought of a long sentence from Sanskrit, a language of which he was entirely ignorant. 'Now take out the paper from your pocket', he said. The Sanskrit sentence was written there! He had written it an hour before with the remark, 'In conformation of what I have written, this man will think of this sentence.' It was correct. Another of us who had been given a similar paper, which he had signed and placed in his pocket, was also asked to think of a sentence. He thought of a sentence in Arabic, which it was, still less possible for the man to know; it was some passage from the Koran. And my friend found this written down on the paper.
Another of us was physician. He thought of a sentence from a German medical book. It was written on his paper.
Several days later I went to this man again, thinking possibly I had been deluded somehow before. I took other friends, and on this occasion also he came out wonderfully triumphant.
Well, I saw many things like that. Going about India you find hundreds of similar things in different places. These are in every country. Even in this country you will find some such wonderful things. Of course there is a great deal of fraud, no doubt ; but then, whenever you see fraud, you have also to say that fraud is an imitation. There must be some truth somewhere that is being imitated; you cannot imitate anything. Imitation must be of something substantially true.
In very remote times in India, thousands of years ago, these facts used to happen even more than they do today. It seems to me that when a country becomes very thickly populated, psychical powers deteriorates. Given a vast country thinly inhabited, th ere will, perhaps, be more of psychical power there. These facts, the Hindus being analytically minded, took up and investigated. And they came to certain remarkable conclusions; that is, they made a science of it. They found out that all these, though e xtraordinary, are also natural; there is nothing supernatural. They are under laws just the same as any other physical phenomenon. It is not a freak of nature that a man is born with such powers. They can be systematically studied, practiced and acquired . This science they call the science of Raja-Yoga. There are thousands of people who cultivate the study of this science, and for the whole nation it has become a part of daily worship.
The conclusion they have reached is that all these extraordinary powers are in the mind of man. This mind is a part of the universal mind. Each mind is connected with every other mind. And each mind, whenever it is located, is in actual communication with the whole world.
Have you ever noticed the phenomenon that is called thought-transference? A man here is thinking something, and that thought is manifested in somebody else, in some other place. With preparations- not by chance- a man wants to send a thought to anothe r mind at a distance, and this other mind knows that a thought is coming, and he receives it exactly as it is sent out. Distance makes no difference. The thought goes and reaches the other man, and he understands it. If your mind were an isolated somethi ng here, and my mind were an isolated something their, and there were no connection between the two, how would it be possible for my thought to reach you? In the ordinary cases, it is not my thought that is reaching you direct; but my thought has got to be dissolved into ethereal vibrations and those ethereal vibrations go into your brain, and they have to be resolved again into your brain, and they have to be resolved again into your own thoughts. Here is dissolution of thought, and there is a resoluti on of thought. It is a roundabout process. But in telepathy, there is no such thing; it is direct.
This shows that there is a continuity of mind, as the Yogis call it. The mind is universal. Your mind, my mind, all these little minds, are fragments of that universal mind, little waves in the ocean; and on account of this continuity, we can convey o ur thoughts directly to one another.
You see what is happening all around us. The world is one of influence. Part of our energy is used up in the preservation of our own bodies. Beyond that, every particle of our energy is day and night being used in influencing others. Our bodies, our v irtues, our intellect, and our spirituality, all these are continuously influencing others; and so, conversely, we are influenced by them. This is going on all around us. Now, to take a concrete example. A man comes; you know he is very learned, his lang uage is beautiful, and he speaks to you by the hour; but he does not make any impression. Another man comes, and he speaks a few words, not well arranged, ungrammatical perhaps; all the same, he makes an immense impression. Many of you have seen that. So it is evident that words alone cannot always produce an impression. Words, even thoughts, contribute only one-third of the influence in making an impression, the man, two-thirds. What you call the personal magnetism of the man- that is what goes out and impresses you.
In our families there are the heads; some of them are successful, others are not. Why? We complain of others in our failure. The moment I am unsuccessful, I say, so-and-so is the cause of the failure. In failures, one does not like to confess one's ow n faults and weaknesses. Each person tries to hold himself faultless and lay the blame upon somebody or something else or even on bad luck. When heads of families fail, they should ask themselves, why it is that some persons manage a family so well and o thers do not. Then you will find that the difference is owing to the man- his presence, his personality.
Coming to great leaders of mankind, we always find that it was the personality of the man that counted. Now, take all the great authors of the past, the great thinkers. Really speaking, how many thoughts have they thought? Take all the writings that h ave been left to us by the past leaders of mankind; take each one of their books and appraise them. The real thoughts, new and genuine, that have been thought in this world up to this time, amount to only a handful. Read in their books the thoughts they have left to us. The authors do not appear to be giants to us, and yet we know that they were great giants in their days. What made them so? Not simply the thoughts they thought, neither the books they wrote, nor the speeches they made, it was something else that is now gone, that is their personality. As I have already remarked, the personality of the man is two-thirds, and his intellect, his words, are but one-third. It is the real man, the personality of the man that runs through us. Our actions are but effects. Actions must come when the man is there; the effect is bound to follow the cause.
The ideal of all education, all training, should be this man-making. But, instead of that, we are always trying to polish up the outside. What use to polish up the outside when there is no inside? The end and aim of all training is to make the man gro w. The man who influences, who throws his magic, as it were, upon his fellow-beings, is a dynamo of power, and when that man is ready, he can do anything and everything he likes; that personality put upon anything will make it work.
Now, we see that though this is a fact, no physical laws that we know of will explain it by chemical and physical knowledge? How much of oxygen, hydrogen, carbon, how many molecules in different positions, and how many cells, etc., etc., can explain t his mysterious personality? And we still see, it is a fact, and not only that, it is the real man; and it is that man that lives and moves his fellow-beings, and passes out, and his intellect and books and works are but traces left behind. Think of this. Compare the great teachers of religion with the great philosophers. The philosophers scarcely influenced anybody's inner man, and yet they wrote most marvelous books. The religious teachers, on the other hand, moved countries in their lifetime. The diff erence was made by personality. In the philosopher, it is a faint personality that influences; in the great prophets it is temendous. In the former we touch the intellect, in the latter we touch life. In the one case, it is simply a chemical process, put ting certain chemical ingredients together, which may gradually, combine and under proper circumstances bring out a flash of light or may fail. In the other, it is like a torch that goes round quickly, lighting others.
The science of Yoga claims that it has discovered the laws, which develop this personality, and by proper attention to those laws and methods, each one can grow and strengthen his personality. This is one of the great practical things and this is the secret of all education.
All over the world there has been the belief in the supernatural through the ages. All of us have heard of extraordinary happenings, and many of us have had some personal experience of them. I would rather introduce the subject by telling you certain facts, which have come within my own experience. I once heard of a man who, if anyone went to him with questions in his mind, would answer them immediately; and I was also informed that he foretold events. I was curious, and went to see him with a few fr iends. We each had something in our minds to ask, and, to avoid mistakes, we wrote down our questions and put them in our pockets. As soon as the man saw one of us, he repeated our questions and gave answers to them. Then he wrote something on paper, whi ch he folded up, asked me to sign on the back, and said, 'Don't look at it; put it in your pocket, and keep it there till I ask for it again'. And so on to each of us. He next told us about some events that would happen to us in the future. Then he said, 'Now, think of a word or sentence, from any language you like.' I thought of a long sentence from Sanskrit, a language of which he was entirely ignorant. 'Now take out the paper from your pocket', he said. The Sanskrit sentence was written there! He had written it an hour before with the remark, 'In conformation of what I have written, this man will think of this sentence.' It was correct. Another of us who had been given a similar paper, which he had signed and placed in his pocket, was also asked to think of a sentence. He thought of a sentence in Arabic, which it was, still less possible for the man to know; it was some passage from the Koran. And my friend found this written down on the paper.
Another of us was physician. He thought of a sentence from a German medical book. It was written on his paper.
Several days later I went to this man again, thinking possibly I had been deluded somehow before. I took other friends, and on this occasion also he came out wonderfully triumphant.
Well, I saw many things like that. Going about India you find hundreds of similar things in different places. These are in every country. Even in this country you will find some such wonderful things. Of course there is a great deal of fraud, no doubt ; but then, whenever you see fraud, you have also to say that fraud is an imitation. There must be some truth somewhere that is being imitated; you cannot imitate anything. Imitation must be of something substantially true.
In very remote times in India, thousands of years ago, these facts used to happen even more than they do today. It seems to me that when a country becomes very thickly populated, psychical powers deteriorates. Given a vast country thinly inhabited, th ere will, perhaps, be more of psychical power there. These facts, the Hindus being analytically minded, took up and investigated. And they came to certain remarkable conclusions; that is, they made a science of it. They found out that all these, though e xtraordinary, are also natural; there is nothing supernatural. They are under laws just the same as any other physical phenomenon. It is not a freak of nature that a man is born with such powers. They can be systematically studied, practiced and acquired . This science they call the science of Raja-Yoga. There are thousands of people who cultivate the study of this science, and for the whole nation it has become a part of daily worship.
The conclusion they have reached is that all these extraordinary powers are in the mind of man. This mind is a part of the universal mind. Each mind is connected with every other mind. And each mind, whenever it is located, is in actual communication with the whole world.
Have you ever noticed the phenomenon that is called thought-transference? A man here is thinking something, and that thought is manifested in somebody else, in some other place. With preparations- not by chance- a man wants to send a thought to anothe r mind at a distance, and this other mind knows that a thought is coming, and he receives it exactly as it is sent out. Distance makes no difference. The thought goes and reaches the other man, and he understands it. If your mind were an isolated somethi ng here, and my mind were an isolated something their, and there were no connection between the two, how would it be possible for my thought to reach you? In the ordinary cases, it is not my thought that is reaching you direct; but my thought has got to be dissolved into ethereal vibrations and those ethereal vibrations go into your brain, and they have to be resolved again into your brain, and they have to be resolved again into your own thoughts. Here is dissolution of thought, and there is a resoluti on of thought. It is a roundabout process. But in telepathy, there is no such thing; it is direct.
This shows that there is a continuity of mind, as the Yogis call it. The mind is universal. Your mind, my mind, all these little minds, are fragments of that universal mind, little waves in the ocean; and on account of this continuity, we can convey o ur thoughts directly to one another.
You see what is happening all around us. The world is one of influence. Part of our energy is used up in the preservation of our own bodies. Beyond that, every particle of our energy is day and night being used in influencing others. Our bodies, our v irtues, our intellect, and our spirituality, all these are continuously influencing others; and so, conversely, we are influenced by them. This is going on all around us. Now, to take a concrete example. A man comes; you know he is very learned, his lang uage is beautiful, and he speaks to you by the hour; but he does not make any impression. Another man comes, and he speaks a few words, not well arranged, ungrammatical perhaps; all the same, he makes an immense impression. Many of you have seen that. So it is evident that words alone cannot always produce an impression. Words, even thoughts, contribute only one-third of the influence in making an impression, the man, two-thirds. What you call the personal magnetism of the man- that is what goes out and impresses you.
In our families there are the heads; some of them are successful, others are not. Why? We complain of others in our failure. The moment I am unsuccessful, I say, so-and-so is the cause of the failure. In failures, one does not like to confess one's ow n faults and weaknesses. Each person tries to hold himself faultless and lay the blame upon somebody or something else or even on bad luck. When heads of families fail, they should ask themselves, why it is that some persons manage a family so well and o thers do not. Then you will find that the difference is owing to the man- his presence, his personality.
Coming to great leaders of mankind, we always find that it was the personality of the man that counted. Now, take all the great authors of the past, the great thinkers. Really speaking, how many thoughts have they thought? Take all the writings that h ave been left to us by the past leaders of mankind; take each one of their books and appraise them. The real thoughts, new and genuine, that have been thought in this world up to this time, amount to only a handful. Read in their books the thoughts they have left to us. The authors do not appear to be giants to us, and yet we know that they were great giants in their days. What made them so? Not simply the thoughts they thought, neither the books they wrote, nor the speeches they made, it was something else that is now gone, that is their personality. As I have already remarked, the personality of the man is two-thirds, and his intellect, his words, are but one-third. It is the real man, the personality of the man that runs through us. Our actions are but effects. Actions must come when the man is there; the effect is bound to follow the cause.
The ideal of all education, all training, should be this man-making. But, instead of that, we are always trying to polish up the outside. What use to polish up the outside when there is no inside? The end and aim of all training is to make the man gro w. The man who influences, who throws his magic, as it were, upon his fellow-beings, is a dynamo of power, and when that man is ready, he can do anything and everything he likes; that personality put upon anything will make it work.
Now, we see that though this is a fact, no physical laws that we know of will explain it by chemical and physical knowledge? How much of oxygen, hydrogen, carbon, how many molecules in different positions, and how many cells, etc., etc., can explain t his mysterious personality? And we still see, it is a fact, and not only that, it is the real man; and it is that man that lives and moves his fellow-beings, and passes out, and his intellect and books and works are but traces left behind. Think of this. Compare the great teachers of religion with the great philosophers. The philosophers scarcely influenced anybody's inner man, and yet they wrote most marvelous books. The religious teachers, on the other hand, moved countries in their lifetime. The diff erence was made by personality. In the philosopher, it is a faint personality that influences; in the great prophets it is temendous. In the former we touch the intellect, in the latter we touch life. In the one case, it is simply a chemical process, put ting certain chemical ingredients together, which may gradually, combine and under proper circumstances bring out a flash of light or may fail. In the other, it is like a torch that goes round quickly, lighting others.
The science of Yoga claims that it has discovered the laws, which develop this personality, and by proper attention to those laws and methods, each one can grow and strengthen his personality. This is one of the great practical things and this is the secret of all education.
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