JPS61501564A - How to treat memory disorders in the elderly - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] How to treat memory disorders in the elderly Background of the invention 1. Field of invention Memory loss is becoming an increasingly common problem with each passing decade. it is very large It occurs in many degenerative brain diseases. Degenerative brain diseases often affect glucose metabolism is associated with disability in Such disorders can lead to confusion and memory loss. may be characterized. Associated with memory loss and also low blood sugar levels The confusion associated with pellagra, Alzheimer's disease, and A late stage of Kinnon syndrome, co-occurring with Fernicke syndrome in alcoholism. Includes Rusakoff syndrome and more or less well-known syndromes. Kwaziorkor and Severe forms of wasting and protein deficiency commonly lead to stupor in their later stages. and deranged and late agonist protein deficiencies can exhibit similar symptomatology. Ru.

The difficulty of explaining and treating these diseases and the dangers of these end-stage diseases Possibility of showing how fundamental metabolic changes underlie economic events. There is.

All attempts to understand glucose metabolism have been Eventually we encounter the recarboxylic acid cycle. Balanced of highly resonant compounds The factors involved in maintaining production and distribution are important in each of the above syndromes. seems to be included.

Description of prior art 2. Prior art ``Monoamine oxidase converts neuroactive amines to inactive aldehydes.'' It is claimed to be a yellow protein oxidase of central abject importance.・・・・・・Hula Bin-bound monoamine oxidase is concentrated in the outer mitochondrial membrane of animal cells (Walsh, No. 402 JN, p. 403). . Effect: Mono Amine oxidase is a complex enzyme system that is widely distributed throughout the body. experiment Drugs that block monoamine oxidase in the chamber are associated with many clinical effects. ing. Therefore, the MAO inhibitor itself, other drugs, the speculative effects of both, or It is not known whether the interaction is responsive to the observed clinical effects.

Therefore, physicians have become familiar with all of the effects produced by this class of drugs. (PDR (Physician's Desk Reference) ians' Desk Reference) 1983) p. 1516].

Two classifications of amine oxidases have been provided. Activity of amine oxidase in seedlings Blanyuko (Bl) used responsiveness to carbonyl inhibitors to distinguish between the sexes. ashko) et al. Zeller (Ze) using semicarpant inhibitor ller) et al. Use of inhibitors to classify amine oxidase in purifying these enzymes and studying the structure of their active site. It reflects the difficulties encountered.

“Existence 0 monoamine oxidase (MAO) has been investigated (1970) in all Classes of dorsal vertebrates: found in clear mammals, birds, reptiles, amphibians, and teleosts. It was brought out (161). The enzyme is found in many different tissues, especially glandular, smooth Occurs in the muscular and nervous systems (162). In humans, the parotid and mandibular glands are M It appears to be the most abundant source of AO (163). It is also molluscs and plants (4)” (Kapeller Adler) ) 31).

Antituberculous drugs were introduced in 1957 to treat depression (June 1981). Article in the New York Times, page B9, March 4). It has been widely researched and It is a noamine oxidase inhibitor. However, in addition to its effect on depression, It had various effects. These issues were raised on a daily basis. Use of these drugs continued to be experimental. Anti-tuberculosis drugs have been removed from the market due to severe liver toxicity. It was. Depression anywhere from a week to a few weeks after these drugs begin treatment It is interesting to note that they have been shown to have a beneficial effect on patients. place to become In some cases, the improvement leads to a state of determination, a state of hypomania, or a state of mania. There is a possibility that it will proceed. Central stimulant effects occur in normal individuals and in patients with depression. and are seen using these drugs (Bevan). Other effects are Orthostatic hypotension, allergic reactions affecting the liver and many cholinergic inhibitors This is a type of symptom.

Disorders in glucose levels have been associated with various diseases. within normal range Glucose maintenance is a substance that lowers its level in glycemia, and various types of It is a substance that increases blood sugar levels in cases of hypoglycemia. Once expressed, true Hyperglycemia in diabetes is usually permanent or becomes so. Hypoglycemia and hyperglycemia It may turn into sexual diabetes. The latter disease has a high morbidity and It is the main cause of death.

Chemical action of monoamine oxidase “Specificity ``The enzyme, isolated from multiple sources, exhibits low specificity.Generally, primary, secondary Primary and tertiary amines, tritamine derivatives and catecholamines are oxidized ( 1.5). However, enzymes isolated from human placenta attack primary amines. and monoalkylamine increase in chain length produces increased affinity. Cheat (7). ” (Barman, p. 180).

``Inhibition of MAO is associated with levels of isoprobil artenelol in the sympathetic nervous system.'' The monoamines serotonin and isoprovir in the monoamine-containing neurons of the CNS. deceives the levels of artenellol and dopamine, leading to a very significant increase... -Multiple amines then accumulate in the cytoplasm. The storage site is quickly depleted of the transmitter. I feel deeply satisfied. Neuroamines in neurons It is assumed that the increased accumulation of is the basis for the depressant effect of MAO inhibitors. . The presence of large amounts of unsubstituted serotonin and 30-methylated catecholamines in the urine It should be added that MAO inhibitor depression is characteristic of excavated patients (viva (Revan, pages 183 and 184). These urine compounds are blood The scavenging of the above amines from The rotation rate corresponds to the rotation rate.

Yellow responsive to oxidative membrane amination of catecholamines (monoamine oxidase) Color proteins are found in a wide variety of tissues and are found primarily in the outer membrane of mitochondria. It is arranged as follows. '(Fr1sell, page 628) Halogenated compounds often enter the body from the environment.

The anesthetics halothane and methoxyflurane are suitable examples. liver microsomes, NA Common anesthetics halothane and methoxyflurane volatile with DPH and oxygen The incubation of (labeled with 15C,4) is accompanied by a large demineralization.

Similarly, thyroxine and triodothyronine are deactivated by liver microsomal enzymes. Receive (8). (Bacq, p. 577). Dimino ) and Hoch (1972) in the liver of rats injected with T4. We found a significant enrichment of iodine in mitochondria.

These mitochondria are more concentrated than those of untreated animals. appear to contain iodine tightly bound to their internal membranes (9 ).

Although the direct action of T4 on isolated mitochondria has been known for some time, However, they occur only at high non-physiological concentrations and their significance is elaborate.

(9)” (Lash (La5h) p. 332). The actual biochemical mechanism of mon action is poorly understood. Multiple production of thyroid hormones It is clear that no single regulatory response was found to explain the effect.

Although the activities of more than 100 enzymes were shown to be affected by tyrosine administration, All appear to be unaffected by the same species degree (10). (Frisse # (Fr1s ell　page 608).

Radiation studies have shown that only 3-4% of the orally administered dose is absorbed by rats. Early studies of greenbelve with manganese (65) showed that. absorbed Manganese is readily expressed in bile and excreted in feces. including humans Experiments since that time with several species have shown that Mann 7 penetrates the intestinal wall by several routes. It is then almost entirely excreted. These pathways are interdependent and Together, efficient dynamic equilibrium mechanisms regulate tissue manganese levels. (16.90.129). In the organization referenced by the first person The relative stability of manganese concentrations is due to such control rather than regulated absorption. (27). '(Uncierwood) p. 184).

Each of these tissues of the intestinal tract actually uses the same system to take in and absorb manganese. It is important to recognize that there are two types of processing.

The above description demonstrates the flux of manganese into and out of mitochondria. It is. It is a reflection of the mitochondrial pool, which is highly unstable It's a pool. Manganese is carried into the plasma bound to proteins. its very A small amount is purified by the kidney store.

Injected radioactive manganese quickly disappears from the bloodstream. Borg ) and Cotzias (28) divided these cleaning into three phases. Divided. The first and fastest of these is normal transcapillary movement. This suggests that the cleaning rate is the same as that of other small ions, and the second is the cleaning rate of tissue mitochondria. The third and slowest entry of manganese into Doria can be identified. The composition can indicate the rate of accumulation of the nucleus of that element, and is useful for blood purification. The kinetic pattern for hepatic absorption of manganese and manganese is (blood manganese and liver mitochondrial manganese) are quickly brought into equilibrium. It shows almost the same thing. A high proportion of manganese in the body is therefore dynamic It must be in a state of mobility. (Underwood) 1st (page 85).

The turnover rate of parenterally administered 54Mn was found to be high in the diet of mice over a wide range. was directly related to stable manganese levels (27). Tracer emission rate A linear relationship between 54Mn and dietary manganese levels was observed and tissue 54Mn The concentration of manganese was directly related to the stable level of manganese in the diet. This is a variable suction The argument that variable excretion, rather than intake, regulates the concentration of this metal in tissues. Provide additional support for. ”(Underwood) p. 185).

``Mechanisms of absorption of manganese from the gastrointestinal tract or excess dietary calcium and Little is known about the means by which phosphorus reduces the effectiveness of manganese... ...Changes in dietary calcium and phosphorus on 54Mn metabolism in rats The effect was further studied by Lasiter and associates (100 ). These researchers found that fecal excretion of parenterally administered Mn was much higher and Liver retention was higher on a 1.0% calcium diet than on a 0.64% 4% calcium diet. It's lower than that. Calcium therefore acts on the retention of absorbed manganese. Affects manganese metabolism, especially by acting on manganese absorption. It seems possible. Changes in dietary phosphorus are associated with excretion of 5'Mn administered i.p. Although it was not possible to compare the effects on It was done. (Underwood, p. 186).

During the 1970s, there was a rush of books on energization in the structure of the mitochondrial membrane. Attention was drawn to the translocations or transports that occurred and to the changes that occurred. Mitochondrial oxidative There was a wide correlation created by sphorylization.

(1975), some of these are due to the fact that a large number of solutes can be transferred to mitochondria without active transport. It was ignored by the flame that crossed the Ndria membrane. protons, phosphates and A number of hypotheses have emerged encompassing other mechanisms for these transports.

In muscle and nerve tissue, 60 millivolts is applied between the inner and outer surfaces of cell membranes. or more. Ca, 1Mg pump describes a wide variety of data Ru.

About highly resonant phosphate compounds that activate mitochondrial cation pumps At first, the data seemed to be good. Such a pump pumps calcium influenced by changes in concentration and it is also regulated by Mg Ru. Mn easily enters and exits mitochondria. It is an activation transition. and with alkaline earth metals.

Other metals participate, but to a lesser extent.

Working in cooperation with Na,/KATPase, (Ca,/) vi Ashiponzo fits into the cell membrane. not only will it have a place in the mitochondrial organization of the object .

Midocon I”J is a primitive substance that is first ingested when cells express phagocytic function. It has long been suggested that it represents a common type of bacteria. Effective oxidation of ingested cells The method is cited as the cause of the manifestation of symbiosis. The corollary of that suggestion is that the first cell developed to correlate the flow between compounds of high resonance between and mitochondria. There is a need to do so. This theory suggests that metabolic diseases are caused by the relationship between the metabolism of two different cells. This suggests that complex metabolic regulation such as this occurs sufficiently. This mechanism of adjustment ism is consistent with that theory.

High efficiency attributed to mitochondria as a source of high resonance coupling It should be further pointed out that Must be. Such a mechanism controls mitochondrial energy production in cells, It must be checked against the energy mechanisms of the organs and, in fact, of the whole organism. Cal Sium is a modulator of the interaction system between mature nuclear cells and myoconglia. It seems to be an inferential choice as a child. This is consistent with the current presentation.

This control mechanism and system was called the regulatory mechanism. Record The order of listed components is cation, ATPase pump, Mn, deiodination. Includes enzymes, thyroid hormones, monoamine oxidases and amines. all are found in close proximity in mitochondria.

combination Addendum In diabetes mellitus, in hypoglycemic disorders, and in relation to glucose in body fluids. This addition was made to facilitate understanding of the use of this method in diseases where associated changes occur. The description will be written. MTA (or CMTA) order in these symptoms Further described.

The digital Journal of the B, O, Society (the J, of the P, O, Soc, ) September 1969, Vol. 52, No. 9, p. 559 Continuing the push of ARCUS), a review of the effective amount of material that should be provided is changing. was most commonly seen with an understanding of the underlying chemical systems. listed here The regulatory mechanisms currently involved in the discussed disease states may be more likely than not. with inherent differences in appropriate line reasoning.

``Dehydrogenation of glutamate is a process in which a portion of many different amino acids are liberated. If the amine group is converted to NH,j/NH3, NH,”t or NH3, then the amine group is Only one fate exists: (1) to be recycled or (2) to be excreted as urine. It can be understood as a major oxidative reaction in the metabolism of living humans. . ' (Fr1sell, p. 240, 1982).

The alpha NH2 group of glutamate can be removed by deamination method. Qualitatively easy to accept. Especially in the liver, alpha ketogel tar acid and NH, There is a highly active dehydrogenase that can respond to the deamination of glutamate to Ru. The enzyme is present in both the cytoplasm and the mitochondria...''( Ibid (yori ta)).

This is due to the rapid glutaminosis both in the sitoturus and in the mitochondria. Causes phosphate destruction. Control mechanisms for enzymes are located in mitochondria It also shows that it may work not only in plants, but also in plants. . This in turn activates dehalogenases in the endoplasmic reticulum to dehydrogenate glutamate in the citrocne. Related to enzymes (glutamate dehydrogenase).

Similarities are associated with glutamate dehydrogenase in the mitochondrial matrix. It is clear that the inner mitochondrial membrane dehalogenase is in close proximity to Therefore, it is inferred that the mechanism for both is the same. in each case Delodenase is inhibited by manganese. Thyroxine as a result The concentration is quite large. Increased thyroxine increases each glutamate dehydrogenase Increase inhibition.

The distance from the endoplasmic reticulum to the glutamate dehydrogenase in the sitotulus is T3 and T4. has a concentration gradient of The same goes from the inner membrane to the mitochondrial matrix. This is true about the distance to glutamate dehydrogenase. If in each case If the distance between The concentrations of T4 and T3 reached will be adequate to cause inhibition.

Such inhibition results in an increase in the amount of metabolism required for biochemical synthesis. this is consistent with the anabolic function of thyroid hormone.

Glutamate dehydrogenase has a thyroxine-associated receptor, possibly allosterin. It is blocked when the target area is occupied. This enzyme lags behind less glutamate. cause destruction. This in turn leads to glutamic acid transamination following amino acid transamination. Delays salt formation. Less glutamate is present as well, such as glutamine and urea. There are fewer formations. Unchanged amino acids are present at high levels in the cellular amino acid pool. remain.

MAO inhibition by thyroxine prevents the destruction of biogenic amines, while glutamine Inhibition of acid salt dehydrogenase activity prevents amino acid destruction. For example, catecholamines While amino acids increase the activity of the cell, the amino acids are It will be effective as a building block. Two groups of substances are for cells) Synchronized for large metabolism.

There is an optimal range within which these metabolisms are synchronized. Beyond that, instability develops. Ru. These are either at the lower or upper levels of normal physiological function. There is a possibility that it is. For example, dogs or humans with toxic goiter may develop diabetes. Hyperglycemia of a sloppy magnitude develops. Appropriateness of normal pattern of target behavior Attention spans may be shortened to the point where they become less attractive and divided. .

Next, to maintain health, the MTA (or CMTA) order should be within normal limits. have to work. Fortunately these limits usually cover a wide range of normal values. Contains.

``The product of glutamic acid, gamma-aminobutyric acid (0ABA), is a neurotransmitter. It is essential for brain function because it slows down the transmission of pulses. GABA is glutami ib is generated due to the loss of the number one carboxyl group of the phosphate salt:... 75% of the total free acids in the brain are aspartate, glutamate and their derivatives. It may be recognized that this can be explained by ′(Frisel( Fr1sell), p. 258 (1982)).

Glutamate is of course synthesized from ammonia and alpha-ketogel tarrate. can be accomplished.

Enzyme from beef liver, 1.4.1.3L ~ Glutamate: NAD (P) oxidation Reductase (deamination), (glutamate dehydrogenase) (Bar; an) (1969, p. 170, vol. 1) is a structural guide to aid such synthesis. actually perform a function in an organization. It is because of the ammonia that goes into the amino acids. This is the gate through which you pass. This is done by feeding cows cut up rough paper and nitrogen Illustrated by using urea as a source.

In 1955, Rose published a book on the literature of the world and especially in the middle of this century. At the end of one of the most important groups of papers published up to this point, there is the following statement: reported on the requirements for nitrogen in cages: ``Recently, it has been determined that nitrogen is the minimum human requirement.'' As a result, the presence of essential elements is reduced and in their place glycine and urea are introduced into the food. It was announced that he would be admitted. Both of the latter compounds serve the purpose in question. (16). human odor There is no reason to doubt that they can perform a similar function. '.

Next, the reported structure and experimental results convincingly supported the claim.

However, as shown, alpha-ketogel tarrates are It is readily formed by salt dehydrogenases as part of the TCA cycle. fact, Alpha-ketogel tarrate from glutamate dehydrogenase is a TCA site. What can be considered stoichiometric in the above background as the return of the initial product to the I can do that.

Lenin, the great mitochondrial analyst and commentator... nger) on glutamate dehydrogenase, page 430 (1970). As mentioned in the next section, 2' probably plays a central role in the transport of amino groups. Therefore, glutamate dehydrogenase is an allosteric enzyme. Beef liver enzyme is 2 It has a molecular weight of 80,000 and has a large number of apparently identical subunits. ing. The enzyme is in a larger aggregate of 2.2 million rod-shaped particles. will be combined into. Equilibrium between monomeric and polyvalent forms can be controlled unidirectionally or by various actuators. or transferred in the other direction. The enzyme is activated by the agonists ATP, GTP, and NADH. It is inhibited by ADP and activated by certain amino acids. It's also Affected by the thyroid hormone thyroxine and certain steroid hormones.

Regarding this, Fr1sell, p. 240 (1982) Thyroid hormone, thyroquinone also affects the activity of glutamate dehydrogenase. However, the significance of this effect has not yet been established. ' There is.

Shortly before that, he ``regarded the macromolecular structure of glutamate dehydrogenation. A prime consists of six identical subunits. As summarized below, the enzyme The unitary property gives it the possibility of being forced into allosteric control. I can do it. In fact, the dehydrogenase can be blocked by NADH, ATP and GTP. "It is stimulated by kDPXGDP and some amino acids."

Ba/l/? y (Barman) Volume 1 (1970) No. 170-171 On pages (1, 4, 1, 3), "Regarding enzymes isolated from bovine liver" GTP and diethylstilbesterol are derived from the following monocarboxylic amino acids, Thialanine, leucine isoleucine, methionine, valine, norleucine, nor It stimulates the oxidation of valine and 2-aminobutyric acid, and ADP blocks these oxidations.

However, glutamate oxidation Although blocked by GTP and diethylstilbesterol, Stimulated by ADP.

These data suggest that the equilibrium between different forms of the enzyme with different relative substrate specificities and that the position of this equilibrium is influenced by the regulator. Conceivable. ′ is somewhat more specific.

Oxidation of monocarboxylic amino acids is dicarboxylic amino acid glutamic acid. You can see what happens when this is not done. The glutamate is It is oxidized when the monocarboxylamino group is not oxidized.

In tabular form, Barman's data can be represented as follows: Can: oxidation Stimulation + inhibition O Beef liver GTP and DES ADP L-glutamate O+ Note: For the reverse reaction, pyruvate is available for growing liver enzymes and bovine liver enzymes. Ru.

To understand the different forms, we use standard terminology Lehninger (Leh (1970) (pp. 58-59). will do.

It is as follows: ``Special terms refer to different features of protein structure or the covalent backbone of leveled chains.'' reference is made to the amino acid residues thereof and in particular their consecutive amino acid residues. The second structure is particularly It is called a polypeptide chain because peptide chains occur in fibrous proteins. The term tertiary structure is The polypeptide chain is bent or folded into a compact structure. The globular protein (Figure 3-2) has a bent structure. ) refers to the combined secondary and tertiary structures of peptide chains in proteins. for A quaternary structure is a protein with more than one chain in which each polypeptide chain is arranged in space. Showing how it is placed or arranged. Either fibrous or spherical Large proteins contain two or more polypeptide chains, between which There is a possibility that there is no covalent bond (Figure 2-2). Generally a polypeptide chain of a protein usually has 100-300 amino acid units (molecular weight 12, ODD~ 36,000”).A few proteins include serum albumin (approximately 550 residues) and It has a longer chain, like myosin (approximately 1,800 residues). However, 5 Any protein with a molecular weight greater than 0,000 has two or more chains. It can then be inferred.

``Proteins with many chains rather than one are known examples of oligomers, which have four polypeptide chains.'' hemoglobin, consisting of a tride chain, two identical alpha chains, and two identical beta chains. It's Robin. Each chain has approximately 140 amino acids. The four chains are covalent bonds together to form a large stable spherical aggregate despite the lack of It fits perfectly. Oligomeric proteins usually contain a uniform number of peptide chains. have From 2 to 12 subunit chains in smaller oligomeric proteins, may exist in either a few dozen or even up to hundreds of large proteins. There is a potential. Tobacco mosaic virus grains have over 2000 peptide chains. Ru.

``Oligomeric proteins are usually two or more proteins that are not covalently linked to each other. Oligomeric proteins are called “molecules” because they contain more than one polypeptide chain. It is inappropriate, or at least inappropriate, to refer to It seems clear, but it doesn't bother me. However, most oligomeric proteins In quality, a complete particle is so solid that it behaves like a single molecule in solution. It is a combination of different particles. In addition, all components of oligomeric proteins Branches or subunits are usually necessary for their function. ′ To bring this further into the big picture in physiological terms and the structural details To enable us to reconcile observed changes in biological function, we Each had even the best extension to the "subunits".

This is what Lenin says on pages 184-185 of Lehninger. Discussed in the paper: This mechanism for hemoglobin oxygenation is a regulatory enzyme. It can be applied directly to the basics. The first substrate molecule for one subunit of a homotrogenic enzyme bond to a first subunit that is mechanically or sterically transferred to a second subunit. There are structural changes that increase the binding of the second substrate molecule to the second subunit. Today In all cases studied in molecule: perhaps the presence of interacting units determines their function. It is necessary for

The term “subunit” is ambiguous and refers to oligomeric proteins. It should be recognized that when applied to quality it may have two different meanings. Hemo Globins have four structural subunits or zolotomers, namely two alpha chains and Although it contains two beta chains, it also contains two functional subunits, i.e. two beta chains. Contains half a rufer beta molecule.

Isozymes ゛Recent research has shown that some enzymes are controlled by features of their molecular structure. revealed other ways in which it can be done. Many different enzymes can also be found within a single building. was found to exist in multiple molecular forms even within a single cell. Such multiple The forms can be detected and separated by gel electrophoresis of cell extracts. they are therefore distinguishable molecular species that differ in net charge. single species Or the multiple forms in the cell are isozymes (or isoenzymes) ) is called.

"Lactate dehydrogenase".

The first widely studied enzyme in this class is found in five different enzymes in rat tissues. It exists in the essential form or isozyme (Figures 9-12). These are obtained in pure form It was. All five inzymes of lactate dehydrogenase catalyze the same overall reaction act but have distinguishable different Km values for their substrates; these differences The biological significance of will be described in Chapters 15 and 18. five isozymes have the same particle mass, approximately 134,000 and all have four polypeptide chains. (each molecular weight 33,500).

If glutamate dehydrogenase is inhibited, less transamination occurs. Koru. This results in less destruction of amino acids with transaminase enzymes. Ru. This is a fact about the inhibition of polymeric forms of glutamate dehydrogenase. However, the monomeric form oxidatively deamines the three branched chain amino acids. Probably Deamination of the methionine chain leads to L-homoserine hero to 2-oxobutyrate. Occurs through lyase (deamination) conversion. This enzyme has HOH added and N It is named homoserine dehydratase where H3 and HOH are the reaction products.

However, methionine and also 2-aminobutyrate are probably glycated in monomeric form. It is listed as a substrate for rutamic acid dehydrogenase. This is □succinyl-CoA poses some questions regarding the pathway of methionine degradation in its ultimate production of wake up Cytonol is a thick suspension. The mitochondrial matrix is very may be a much thicker suspension with a higher protein content. Like that From the viewpoint of the monomer of glutamate dehydrogenase that is produced in a This is consistent with the idea of methionine destruction not involving a B-6 assisted step.

Lysine and threonine are two essential amino acids that are not transaminated. Ru. In fact, they are not easily destroyed. Lysine forms an organic electrolyte, polyamine is required for the formation and transport of branched-chain fatty acids into the mitochondria. for the synthesis of carnitine, which is necessary for carnitine acyltransferase activity. The overall effect of the enzymatic process will be to increase the demand for branched chain amino acids. death Therefore, the two aromatic amino acids, phenylalanine and tryptophan, are glutamate. Saved by inhibition of mate dehydrogenase. On the other hand, valine, inleucine, leucine The initial sparing of methionine and It can be changed depending on the monomer of the enzyme to be minated. Under these circumstances, the savings effect increases and increase the need for these amino acids. at least However, currently, threonine degrades to the extent that it becomes succinyl-CoA. Also, the amino acids may have a sparing effect on the polymeric form or blocked glutamate. It seems likely that some of the increased degradation of the monomeric form of dehydrogenase is involved. Not possible. Lysine is purely ketogenic. to the acetyl-CoA pool Its contribution would seem irreversible under these circumstances.

Alpha-ketogel tarrate is inocitrate dehydrogenation in TCA cycle Formed by an enzyme (isocitrated dehydrogenase) . This pool is expanded by the action of glutamate dehydrogenase. alpha Ketogel tarrate dehydrogenase (alpha-ketoglutarate) dehydrogenase) quickly converts it to succinyl-CoA. Ru. Next, succinyl-CoA is produced by succinyl-CoA synthetase (5yntheta se) to succinic acid, and at the same time the GTP molecules are converted into GDP and Pl. formed from.

Rate-limiting citrate nontase (5ynthase) in the TCA cycle In discussing the process, Frisel (engineer) ``The synthase reaction has hitherto been accepted as a nonequilibrium reaction and is the main component for the cycle. It's becoming a control reaction. The rate of the synthase reaction depends on the use of acetyl-CoA. It makes sense to be sensitive to your needs. However, even more cycle succinyl-CoA, an intermediate in the body, inhibits citrate synthesis by competition with active acetate. prevent. ' he said.

This means that the size of the pools of acetyl-CoA and succinyl-CoA increases during the TCA cycle. It is possible to estimate the primary importance in measuring the overall proportion of It suggests that. Many substances are degraded to succinyl-CoA.

these are: 1. Inleucine and valine via methylmalonyl-CoA 2. Branched chain via propionyl CoA which is then converted to methylmalonyl CoA fatty acid 3. Methionyl via alpha ketogel tarate to propionyl CoA and tryptophan. Methylmalonyl-CoA is produced by the action of mutase. is rearranged to form succinyl-CoA. This conversion of the enzyme to become active B-12 is required for this purpose. The reaction for fluorionyl-CoA itself is biotinylated. Requires a link.

4. Pyrimidine destruction products from thymine, including these, are also succinyl C Contribute to oA.

Polymeric glutamate dehydrogenase produces alpha-11 ketogel tarrate (2- The point of indirectly feeding into this pool through shredded. When the polymeric form is loaded, the heptad-mer form increases the destruction of the above amino acids. Much as if the polymer form would replace what was lost if it were blocked. Generate Zaku/Nil-CoA as follows.

Summary of the invention The present invention aims to improve degeneration, especially in the elderly, where memory loss and low blood sugar levels commonly occur together. Provided for the use of methods of increasing blood glucose levels in sexual brain diseases Ru. The use of hyperglycemic effects of various amino acids together with manganese in effective proportions is chemical hypoglycemia and hypoglycemia as part of the syndrome. Returning normal levels of glucose to patients with degenerative brain disease that occurs with glycemia In its relation to a given effective amount, the present invention is used for There is a pattern of varying amounts and frequency of administration to afflicted individuals. It differs in that it is constantly changing, just like it is.

How to use this method Description of preferred embodiments How to study geriatric patients with memory impairment is important to understand how vulnerable patients are and how A clear idea of what other illnesses may complicate the clinical plan is required. It is. If the clinician is satisfied with the use of common stimuli, the first effort should be to The goal should be to precisely specify the state of the substitution injection.

These disorders are found across a wide spectrum of clinical diseases. death Therefore, numerous small emboli in the brain from vascular atherosis are associated with Alzheimer's disease. and may result in a general loss of memory, which is common with that in other diseases. be. Of all the syndromes, Alzheimer's syndrome is the most common and hundreds of Including 10,000 patients. The decline course lasts on average about 6 years. Arnoheimer's patients have a flat glucose tolerance curve indicating hypoglycemia during that portion of the test. Artsakh The greatest difficulty in developing a plan for Immel's disease is confusion and confusion about the diagnosis. It arose from the constant demand that this, that, or the other treatment was effective.

It is notable for the lack of effective treatments and the majority of ineffective treatments. this The confusion has probably hastened the current clinical crisis on a large scale. False hope is that be encouraged to treat diseases in such a way as to bring them into a true state of knowledge regarding It reflected reluctance on the part of those who

Hypotension is a hallmark of the disease. Expansion pressures are uniformly low.

the back of the brain where neurons have the highest need for oxygen of all cells in the body The onset of a slow progressive loss of cells on the parietal and parietal areas is a sign of repeated intermittent metabolic failure. and this is in good agreement with the finding of a flat glucose tolerance curve. I will.

Hypoglycemia in many alcoholics, in memory impairment in alcoholism It may be helpful to remember that these are commonly found. That syndrome continued properly. If you receive vitamin treatment many times, you will receive a wide response. however, develops memory loss Alcoholics often remain with significant memory deficits as well.

Patients with the disease often experience periods of confusion and agitation. child These are probably due to a surge in arenarin secretion to overcome the initial glucose drop. as due to falling glucose causing reactive hypoglycemia followed by best explained. Glucose drops, adrenaline is released, and glucose The blood pressure rises and insulin is released again. The borderline level is above If an adrenaline rush occurs in the situation described above, help the patient overcome confusion. It's not enough.

If long duration GTTs of 8 hours or less are used, there may be no adverse effects on the patient. Therefore, it is necessary to discontinue the test. necessary to assess the patient's condition. The key is to control glucose levels, and therefore to control hypoglycemia. Is Rukoto. This condition has the same problem. Many of largely limited effectiveness Treatment is available and reliable and effective treatment has never been available before. Glucose levels are The primary effort should be to return glucose levels to normal, as they can be effectively raised. It should be. However, various amino acids have not yet been effectively used. It is necessary to realize the pursuit of a transition in the function of the noic acid pump.

The combined electrolyte changes that occur as the hypoglycemia returns to normal blood sugar are the response. the relative amounts of amino acids transferred may be aromatic relative to each other; As the ratio of group amino acids as well as the ratio of amino acids in other groups is varied. Change.

If blood sugar is increased, blood pressure may increase as well. this is not treated and return to the original blood pressure level after the glucose level has stabilized at the desired normal level. calm down. For this reason, we raise blood sugar in small steps and in small increases. It is useful to The interval between such changes in level is one week or so. It may be more than that. The patient's general situation must be considered. but However, these drugs are cumulative and should not be treated beyond the desired point. is the most important. Therefore, step-by-step measures should be taken to prevent such situations from occurring. A treatment plan can help.゛This also requires the clinician to personally supervise the treatment plan. Clearly emphasize the importance. One way to do this is to monitor your blood sugar continuously before meals. by using and giving the medication while the patient is eating a meal. such food Things should contain high potency protein.

Identification of some of these syndromes restore normoglycemia and then reassess the patient's condition. This is achieved by

Because of changes in the function of large neutral amino acid bongs that contain many essential amino acids , to assess when the patient's amino acid balance has settled down to its current state. is sometimes necessary. The nonpolar residues of amino acids are often essential amino acids. It is an acid (-) which means that these amino acids are used for the synthesis of the active site of the enzyme. emphasize the great importance of

Treatment must be guided to give the patient a small eye.

The use of valine is essentially associated with neuromuscular disorders.

These themselves are common and progressive in Arnoheimer's disease and Parkinson's disease. Diagnostically expressed in changes in handwriting that deteriorates. its use and combination There appears to be a pronounced combined demand effect. However, the use of valine has been Submit honorarium consideration. Roynone is derived from valine and beta- from branched chain fatty acids. It is formed via a leuzycobalamin-dependent shunt (5hunt). of leucine The hypoglycemic effect is therefore enhanced by valine as a reserve source of leunon.

On the other hand, if there is no shortage of leucine, this should not be a problem. However While controlling the glucose value within an appropriate range, e.g. It seems best to ensure a large amount of L-isoleucine under the given circumstances. The following is an example. The amount can be increased for a while, but then decreased I have to let it happen. No effort is made to restore the inoleucif/leucine ratio to the normal range. Must not be too expensive.

Most cases of memory loss in the elderly are caused by Chief Justice Holmes. Due to handwritten changes such as those described by Ice Holmes be accompanied. In an effort to correct the disorders that lead to handwriting deterioration, It is best to focus your efforts on leucine and then use L-valine later.

The amount given should always be small, increasing gradually and then depending on the patient's needs. It will be tapered off as needs are met. This applies to each substance used .

Characteristically lower blood curves are found in degenerative brain diseases of the elderly. Here Among the diseases mentioned, all other than the atheroma syndromes mentioned have lower curves. It's falling. Even in Parkinson's disease, this means that the medications used may alter blood sugar levels somewhat. characterized by memory loss, although it is often misdiagnosed because of there is a possibility. Levels in patients at base level are low for glucose It tends to be.

Example≠1 shows the treatment of an individual with low blood sugar levels but no memory loss problems provided for. The patient is nearing retirement age and has a full and active job. He led a life of

Example + i Patients M, V.

Clinical situation: Patient has a long history of low, flat glucose tolerance tests There is.

Values were particularly low in the previous year.

However, they are in the range of 50m9. remains within the range and its low Normal level of blood sugar glucose level Attempts to change the range It was done.

Treatment period: Hashime underwent two days of treatment over the weekend. then next three weeks while It was done many times.

Treatment period intervals - range from 1 week to 2 days.

Objective observation: I Blood glucose: from about 5 milligrams/100 milliliters (rw%) upwards 100 towards over a range of mysi.

■ Suppression: A-systolic pressure: ranges from 150 to 124In9Hg (millimeter water silver pressure).

B expansion pressure: ranges from 86 to 110 to 75 mmHg in order.

C pulse pressure: ranges from 90 to 34 mmHg.

■ Pulse 2 Ranges from 70 to 7 Otsu.

Scope of medication: Rate: Manganese (In9 manganese curconate) 2m at intervals of 1-10 days g+.

Isoleucine - in locks, handcuffs and one tablet.

500 between meals within 10 days m9/tablet (body weight 1 m9) (0,007-0.27 Purpose of treatment: To lower glucose levels from (100-110) to (140-150) m 9% normal Bringing to the range.

Subjective observations: The patient was anxious and healthy during the period with upper respiratory infection. harm the Ta. During this time anxiety was noticeable.

Clinical response: Episodes of unstable blood pressure occur during the included period and then 2 weeks Up to 124/75 over the period It went down and fluctuated. blood glucose water Changes in standards occurred easily.

The most striking observation is that the level of 9 orng chi was still present after 6 months. It was.

patient was his usual pattern Feeling much better day by day It continued.

Submission of translation of written amendment (Article 84-7, Paragraph 1 of the Patent Act)

Claims (1)

[Claims] 1. (a) L-valine, D-valine, L-methionine in a ratio effective for memory enhancement; , D-methionine, L-isoleucine, D-inleucine, their alphas -keto and alpha-hydroxy analogs and their amino acids di- and tripe at least one of peptides or pharmaceutically acceptable acid addition salts thereof; a memory-enhancing effective amount of the species compound and (b) L-phenylalanine. , L-tyrosine, D-phenylalanine, D-tyrosine, their alpha- Keto and alpha-hydroxy analogues and their amino acids di- and tripep At least one of tide or a pharmaceutically acceptable acid addition salt thereof (C) a preparation consisting essentially of a manganese compound; consisting of administering to the afflicted patient together with an effective non-lethal dose thereof. How to treat memory loss in dorsal vertebrates.