Creatine creatinine levels, serum or plasma quantitative,testosterone increasing exercises list,testosterone metabolism in the skin - New On 2016

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Creatine kinase is the enzyme responsible for swapping the phosphate groups (shown in red) between PCr and ATP. Creatine and PCr later spontaneously degrade into creatinine, which is able to escape from the cell. The production of ATP from PCr has the added advantage that it also neutralizes muscle acidity (H+).
Legend: The presence of charged groups on creatine and PCr prevent them from transversing the muscle membrane. Also note that most of the muscle creatine is in the form of PCr, which also degrades at twice the rate of creatine. Learn how to best combine exercise, nutrition, and intelligent creatine use for maximal muscle growth and improved athletic performance. The next time you step away from your desk for a quick coffee, your computer can get to work…doing calculations for Muscular Dystrophy research. The majority of tyrosine that does not get incorporated into proteins is catabolized for energy production. Tyrosine is transported into catecholamine-secreting neurons and adrenal medullary cells where catechaolamine synthesis takes place.
Once synthesized, dopamine, norepinephrine and epinephrine are packaged in granulated vesicles. Metabolism of the catecholemines occurs through the actions of catecholamine-O-methyltransferase, (COMT) and monoamine oxidase, (MAO). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT, see also Biochemistry of Nerve Transmission) and melatonin (N-acetyl-5-methoxytryptamine).
Serotonin is synthesized through 2-step process involving a tetrahydrobiopterin-dependent hydroxylation reaction (catalyzed by tryptophan-5-monooxygenase) and then a decarboxylation catalyzed by aromatic L-amino acid decarboxylase. Serotonin is present at highest concentrations in platelets and in the gastrointestinal tract. Melatonin is derived from serotonin within the pineal gland and the retina, where the necessary N-acetyltransferase enzyme is found. Creatine is synthesized in the liver by methylation of guanidoacetate using SAM as the methyl donor. Glutathione (abbreviated GSH) is a tripeptide composed of glutamate, cysteine and glycine that has numerous important functions within cells.
The role of GSH as a reductant is extremely important particularly in the highly oxidizing environment of the erythrocyte. One of the earliest signals that cells have entered their replication cycle is the appearance of elevated levels of mRNA for ornithine decarboxylase (ODC), and then increased levels of the enzyme, which is the first enzyme in the pathway to synthesis of the polyamines.
The key features of the pathway are that it involves putrescine, an ornithine catabolite, and S-adenosylmethionine (SAM) as a donor of 2 propylamine residues. The signal for regulating ODC activity is unknown, but since the product of its activity, putrescine, regulates SAM decarboxylase activity, it appears that polyamine production is principally regulated by ODC concentration. The butylamino group of spermidine is used in a posttranslational modification reaction important to the process of translation. Vasodilators, such as acetylcholine, do not exert their effects upon the vascular smooth muscle cell in the absence of the overlying endothelium. Nitric oxide is involved in a number of other important cellular processes in addition to its impact on vascular smooth muscle cells.
NOS is a very complex enzyme, employing five redox cofactors: NADPH, FAD, FMN, heme and tetrahydrobiopterin. Creatine is quickly becoming one of my favorite supplements, and not just because of the way it helps me in the gym. Back in the early 1990s it became common for bodybuilders, wrestlers, sprinters and other athletes to take creatine as word got out that it contributed to increased muscle mass and energy.
In fact, research shows that creatine is most effective in high-intensity training and explosive activities. Recently I have switched from being an occasional user of creatine (3000 mg per day, cycling monthly) to a daily low dosage user (750 to 1500 mg per day every day) while on a high protein diet. Moreover, while creatine can be used as a strength enhancer and a cognitive booster, it may also have an important role in the prevention and treatment of neurodegeneration. As much as I'd like to take creatine, I have recurrent GERD, and for those of us with that condition creatine is a nasty trigger. Canadian futurist, science writer, and ethicist, George Dvorsky has written and spoken extensively about the impacts of cutting-edge science and technology—particularly as they pertain to the improvement of human performance and experience. The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. The goal of this article is to provide a comprehensive overview on the physiology and pathology of Cr and Crn metabolism. In fast-twitch skeletal muscles, a large pool of PCr is available for immediate regeneration of ATP hydrolyzed during short periods of intense work. Heart, slow-twitch skeletal muscles, or spermatozoa, on the other hand, depend on a more continuous delivery of high-energy phosphates to the sites of ATP utilization. Although the shuttle hypothesis seems logical and intelligible on first sight, there is an ongoing debate on whether it accurately describes the function of the CK system in endurance-type tissues (524, 837, 964). PCr and Cr, relative to ATP and ADP, are smaller and less negatively charged molecules and can build up to much higher concentrations in most CK-containing cells and tissues, thereby allowing for a higher intracellular flux of high-energy phosphates.
Schematic representation of the reactions and enzymes involved in vertebrate creatine and creatinine metabolism.
Many of the lower vertebrates (fish, frogs, and birds) have both AGAT and GAMT in their livers and often also in the kidneys (see Refs. Several lines of experimental evidence, however, demonstrate that this concept of the organization of Cr metabolism is too simplistic. On the other hand, GAMT mRNA and protein levels higher than those observed in male liver were detected in mouse testis, caput epididymis, and ovary (see Ref.
A specific, saturable, Na+- and Cl?-dependent Cr transporter responsible for Cr uptake across the plasma membrane has been described for skeletal muscle, heart, smooth muscle, fibroblasts, neuroblastoma and astroglia cells, as well as for red blood cells and macrophages (149, 150, 250,570, 659, 711, 876,965). An important aspect of Cr biosynthesis to add is that in humans, the daily utilization of methyl groups in the GAMT reaction approximately equals the daily intake of “labile” methyl groups (Met + choline) on a normal, equilibrated diet (671). The highest levels of Cr and PCr are found in skeletal muscle, heart, spermatozoa, and photoreceptor cells of the retina. A, ¦), which might be due to an involvement of the Cr transporter in the resorption of Cr from the primary urine.2) Liver has a considerably lower CK activity than expected from its Cr content (Fig.
B, ?), which may be an expression of a strict separation between Cr-synthesizing and CK-expressing tissues in the body. After donating its energy allotment to the contractile apparatus of muscle, ATP becomes ADP (Adenosine DiPhosphate). The upward reaction predominates during strenuous exercise when energy (ATP) is needed to fuel explosive movements. This effect should heighten our fatigue threshold during moments of intense physical exertion.
Creatinine, by contrast, has no charge and is thus able to freely slip through the muscle membrane escaping to the outside. These methods of helping mankind won’t cost you a cent, nor will they interfere with your daily routine. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals.
They are also involved in regulating blood pressure, electrolyte balance, and red blood cell production in the body. Both norepinephrine and the methylated derivative, epinephrine are stored in synaptic knobs of neurons that secrete it, however, epinephrine is not a mediator at postganglionic sympathetic endings. The first step in the process requires tyrosine hydroxylase, which like phenylalanine hydroxylase requires tetrahydrobiopterin as cofactor. Within these vesicles, norepinephrine and epinephrine are bound to ATP and a protein called chromogranin A.
The hydroxylase is normally not saturated and as a result, an increased uptake of tryptophan in the diet will lead to increased brain serotonin content.
The phosphate of ATP is transferred to creatine, generating creatine phosphate, through the action of creatine phosphokinase. Creatinine is formed in muscle from creatine phosphate by a nonenzymatic dehydration and loss of phosphate. It serves as a reductant, is conjugated to drugs to make them more water soluble, is involved in amino acid transport across cell membranes (the g-glutamyl cycle), is a part of the peptidoleukotrienes, serves as a cofactor for some enzymatic reactions and as an aid in the rearrangement of protein disulfide bonds. Many are symport or antiport mechanisms that couple amino acid transport to sodium transport. Because of the latter, and because the polyamines are highly cationic and tend to bind nucleic acids with high affinity, it is believed that the polyamines are important participants in DNA synthesis, or in the regulation of that process.
The first propylamine conjugation yields spermidine and addition of another to spermidine yields spermine. At the same time, SAM decarboxylase cleaves the SAM carboxyl residue, producing decarboxylated SAM (S-adenosymethylthiopropylamine), which retains the methyl group usually involved in SAM methyltransferase activity.
When acetylcholine binds its receptor on the surface of endothelial cells, a signal cascade, coupled to the activation phospholipase C-g (PLCg), is initiated. Events initiated by NO that are important for blood coagulation include inhibition of platelet aggregation and adhesion and inhibition of neutrophil adhesion to platelets and to the vascular endothelium. NO can also be formed from nitrite, derived from vasodilators such as glycerin trinitrate during their metabolism.

It's been shown that creatine can also be used as a nootropic and as a way to stave off potential neurodegeneration. Athletes began to consume two to three times the amount that could be obtained from a high protein diet. This includes weight training and sports that require short bursts of effort, such as sprinting, football, and baseball. I've done this for cost reasons while still hoping to take advantage of its benefits, which aren't just limited to the physical realm.
It's been shown to boost brain performance, including positive impacts on working intelligence and memory—both of which require improved cognitive processing speed. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases.
In contrast, Cr (from greekkreas, flesh) metabolism in general has attracted considerably less attention.
Because of the high cytosolic CK activity in these muscles, the CK reaction remains in a near-equilibrium state, keeps [ADP] and [ATP] almost constant (over several seconds), and thus “buffers” the cytosolic phosphorylation potential that seems to be crucial for the proper functioning of a variety of cellular ATPases.
In accordance with these ideas, the proportion of Mi-CK seems to correlate with the oxidative capacity of striated muscles.
Therefore, the buffer and transport models for CK function should be regarded neither as strictly true nor as static views that can be applied directly to any one tissue; rather, the CK system displays a high degree of flexibility and is able to adapt to the peculiar physiological requirements of a given tissue. 2), the situation is complicated by the fact that most tissues lack several of the enzymes required, thus necessitating transport of intermediates between the tissues through the blood to allow the whole cascade of reactions to proceed. In the course of evolution, both AGAT and GAMT seem to have evolved with the appearance of the lampreys (1056). The asterisk indicates the nitrogen atom to which a methyl group from S-adenosyl-l-methionine is transferred by GAMT to yield Cr.
Pyridoxine-deficient rats, despite a 65% decrease in kidney AGAT activity relative to controls, displayed increased liver and skeletal muscle concentrations of Cr (572).
These findings have recently been corroborated by cDNA cloning and Northern blot analysis of the rabbit, rat, mouse, and human Cr transporters (295, 319,415, 543, 691, 697,840, 860, 927).
Even if de novo Met biosynthesis also is taken into account, Cr biosynthesis still accounts for ?70% of the total utilization of labile methyl groups in the body.
Intermediate levels are found in brain, brown adipose tissue, intestine, seminal vesicles, seminal vesicle fluid, endothelial cells, and macrophages, and only low levels are found in lung, spleen, kidney, liver, white adipose tissue, blood cells, and serum (61,127, 175, 525, 547,568, 570, 693, 759,1080, 1082, 1083,1108, 1136).
During intense physical exertion ATP is rapidly recreated from ADP by the donation of a phosphate group from Phosphocreatine (PCr). The downward reactions primarily takes place during moments of rest and recreates our PCr reserves. This leakage pathway sets our requirement for new creatine (~2 grams per day, also see Chapter 4 of my creatine guide for greater explanation).
There he was involved in research in radiation biology and received the Huisking Scholarship.
The catecholamine neurotransmitters are dopamine, norepinephrine, and epinephrine (see also Biochemistry of Nerve Transmission). Serotonin containing neurons have their cell bodies in the midline raphe nuclei of the brain stem and project to portions of the hypothalamus, the limbic system, the neocortex and the spinal cord. The 5HT2C receptors are suspected in control of food intake as mice lacking this gene become obese from increased food intake and are also subject to fatal seizures.
Synthesis and secretion of melatonin increases during the dark period of the day and is maintained at a low level during daylight hours.
The amount of creatinine produced is related to muscle mass and remains remarkably constant from day to day. The resulting oxidized form of GSH consists of two molecules disulfide bonded together (abbreviated GSSG).
SAM decarboxylase activity is regulated by product inhibition and allosterically stimulated by putrescine. Following the modification the residue is hydroxylated yielding a residue in the protein termed hypusine. The PLCg-mediated release of inositol trisphosphate, IP3 (from membrane associated phosphatidylinositol-4,5-bisphosphate, PIP2), leads to the release of intracellular stores of Ca2+. NO is also generated by cells of the immune system and as such is involved in non-specific host defense mechanisms and macrophage-mediated killing.
Another important cardiovascular effect of NO is exerted through the production of cGMP, which acts to inhibit platelet aggregation. Because earlier reports of damage to the kidneys and liver by creatine supplementation have now been scientifically refuted, creatine is becoming increasingly accepted as a powerful and multi-faceted daily supplement. Creatine, which is typically bought in pills or flavored powders and mixed with liquid, increases the body's ability to produce energy rapidly.
As a CrossFitter and an occasional user of creatine, I can certainly vouch for these effects. Back in 2003, a study showed that people who took creatine for six weeks scored better on tests measuring intelligence and memory than those who did not take it. It's also being used by Parkinson's patients as way to slow the progression of the disease.
Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer.
The ?-phosphate group of ATP, synthesized within the mitochondrial matrix, is transferred by Mi-CK in the mitochondrial intermembrane space to Cr to yield ADP plus PCr.
It is by far higher in heart (up to 35% of total CK activity) than in fast-twitch skeletal muscles (0.5–2%). In skeletal muscle, for example, an adaptation of the CK system from a more buffer to a more transport type can be induced by endurance training or by chronic electrical stimulation (26, 861). These enzyme activities were not detected in invertebrates, whereas they are found in most but not all vertebrates examined. In mammals, pancreas contains high levels of both enzymes, whereas kidneys express fairly high amounts of AGAT but relatively lower levels of GAMT. Because muscle has virtually no Cr-synthesizing capacity, Cr has to be taken up from the blood against a large concentration gradient by a saturable, Na+- and Cl?-dependent Cr transporter that spans the plasma membrane (?). In another study, extrarenal synthesis was suggested to account for 40–60% of total Cr (290). Likewise, Sertoli cells of rat seminiferous tubules, in contrast to germ cells and interstitial cells, were shown to synthesize guanidinoacetate and Cr from Arg and Gly (664). Upon lowering of the Met and choline levels in the diet, the deficit in labile methyl groups is compensated for by increased de novo Met biosynthesis, indicating that the delivery of labile methyl groups, in the form of S-adenosyl-l-methionine, should normally not become limiting for Cr biosynthesis.
A fairly good correlation seems to exist between the Cr transporter mRNA level and total CK activity which, in turn, also correlates with the tissue concentration of total Cr (Cr + PCr; Fig. Creatinine is produced from creatine, a molecule of major importance for energy production in muscles. DOPA decarboxylase converts DOPA to dopamine, dopamine b-hydroxylase converts dopamine to norepinephrine and phenylethanolamine N-methyltransferase converts norepinephrine to epinephrine.
After release from serotonergic neurons, most of the released serotonin is recaptured by an active reuptake mechanism.
This diurnal variation in melatonin synthesis is brought about by norepinephrine secreted by the postganglionic sympathetic nerves that innervate the pineal gland. Creatinine is excreted by the kidneys and the level of excretion (creatinine clearance rate) is a measure of renal function. The enzyme glutathione reductase utilizes NADPH as a cofactor to reduce GSSG back to two moles of GSH. Spermidine synthase catalyzes the condensation reaction, producing spermidine and 5'-methylthioadenosine. In turn, the elevation in Ca2+ leads to the liberation of endothelium-derived relaxing factor (EDRF) which then diffuses into the adjacent smooth muscle.
This is because it is a highly reactive free radical and interacts with oxygen and superoxide. Creatine is naturally produced in the human body from amino acids primarily in the kidney and liver and is transported in the blood for use by muscles. I believe that creatine is responsible for adding as much as five to twenty pounds to my lifts (depending on the kind of lift) along with an added boost of muscular endurance—two very desirable qualities for CrossFit athletes. And interestingly, some of the most significant cognitive benefits are experienced by vegetarians and vegans, probably on account of protein deficiencies (which has an impact on the body's ability  produce creatine naturally). These effects, combined with its beneficial impacts on strength and endurance (both important health factors for longevity), lead me to believe that creatine is an indispensable part of any life extension strategy. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. For instance, Cr analogs have proven to be potent anticancer agents that act synergistically with currently used chemotherapeutics.
It is our hope that this review will stimulate future multidisciplinary research on the physiological functions of the CK system, on the pathways and regulation of Cr metabolism, and on the relationships between disturbances in Cr metabolism and human disease.
This concept may reflect the situation in tissues devoid of CK and PCr, like liver, but is clearly inadequate for CK-containing tissues with high and fluctuating energy demands like skeletal or cardiac muscle, brain, retina, and spermatozoa.
ADP liberated by the Mi-CK reaction may directly be transported back to the matrix where it is rephosphorylated to ATP. On the contrary, livers of all mammalian species tested so far contain high amounts of GAMT but display only low levels of Cr and almost completely lack CK activity. The daily demand for Cr is met either by intestinal absorption of dietary Cr or by de novo Cr biosynthesis.

Similarly, comparison of the hepatic and renal venous levels with the arterial levels of Arg, GAA, and Cr suggested that in humans, the liver is the most important organ contributing to biosynthesis of both GAA and Cr, whereas the kidney plays only a secondary role (842).
It may therefore be hypothesized that the Cr-synthesizing machinery in reproductive organs plays a role in the development or function of germ cells. He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine.
This latter reaction is one of several in the body that uses SAM as a methyl donor generating S-adenosylhomocysteine.
The function of the antidepressant, Prozac is to inhibit this reuptake process, thereby, resulting in prolonged serotonin presence in the synaptic cleft.
Most of these receptors are coupled to G-proteins that affect the activities of either adenylate cyclase or phospholipase Cg (PLCg). Also present in the gastrointestinal tract are 5HT4 receptors where they function in secretion and peristalsis. Hence, the pentose phosphate pathway is an extremely important pathway of erythrocytes for the continuing production of the NADPH needed by glutathione reductase.
Within smooth muscle cells, EDRF reacts with the heme moiety of a soluble guanylyl cyclase, resulting in activation of the latter and a consequent elevation of intracellular levels of cGMP. Additional cellular responses to NO include induction of apoptosis (programmed cell death), DNA breakage and mutation. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins.
Cyclocreatine, one of the Cr analogs, as well as PCr protect tissues from ischemic damage and may therefore have an impact on organ transplantation. In these latter tissues of mammals and birds, four distinct types of CK subunits are expressed species specifically, developmental stage specifically, and tissue specifically.
PCr leaves the mitochondria and diffuses through the cytosol to the sites of ATP consumption. Citrulline, synthesized in the liver or small intestine and transported through the blood, is taken up by the kidney and converted into Arg mainly by the proximal tubule of the nephron (273, 553). This implies that these species either accumulate Cr from the environment or from the feed, or that the enzymes for Cr biosynthesis in these animals escaped detection so far. Although livers of cow, pig, monkey, and human also have high amounts of AGAT, livers of common laboratory mammals such as the rat, mouse, dog, cat, and rabbit were reported to lack AGAT activity.
The first step of Cr biosynthesis probably occurs mainly in the kidney, whereas the liver is likely to be the principal organ accomplishing the subsequent methylation of guanidinoacetic acid (GAA) to Cr. In accordance with these observations, immunofluorescence microscopy revealed significant amounts of AGAT not only in rat kidney and pancreas, but also in liver (623). GAMT activity was also detected in rat spleen, heart, and skeletal muscle, in sheep muscle, as well as in human fetal lung fibroblasts and mouse neuroblastoma cells (149, 1130, 1135,1136). Within the substantia nigra and some other regions of the brain, synthesis proceeds only to dopamine. This leads to increased levels of cAMP, which in turn activate the N-acetyltransferase required for melatonin synthesis. In fact as much as 10% of glucose consumption, by erythrocytes, may be mediated by the pentose phosphate pathway. The enzyme g-glutamyl transpeptidase is located in the cell membrane and shuttles GSH to the cell surface to interact with an amino acid.
The net effect is the activation of cGMP-responsive enzymes which lead to smooth muscle cell relaxation.
These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system. Circumstantial evidence suggests a link between disturbances in Cr metabolism and muscle diseases as well as neurological disorders, and beneficial effects of oral Cr supplementation in such diseases have in fact been reported. The cytosolic M-CK (M for muscle) and B-CK (B for brain) subunits form dimeric molecules and thus give rise to the MM-, MB-, and BB-CK isoenzymes.
There cytosolic CK isoenzymes locally regenerate ATP and thus warrant a high phosphorylation potential in the intimate vicinity of the respective ATPases.
Arg formed within the kidney is then either released into the blood and consumed by other tissues or used within the kidney itself for guanidinoacetate synthesis. On the basis mostly of these latter findings and of the fact that the rate of Cr biosynthesis is considerably reduced in nephrectomized animals (248,291, 554), it was postulated, and is still largely accepted, that the main route of Cr biosynthesis in mammals involves formation of guanidinoacetate in the kidney, its transport through the blood, and its methylation to Cr in the liver (Fig.4). It must be stressed that the detailed contribution of different bodily tissues (pancreas, kidney, liver, testis) to total Cr synthesis is still rather unclear and may vary between species (see text). The apparent discrepancy from earlier investigations may be explained by the high levels of liver arginase interfering with AGAT activity assays. Although the specific activities in these tissues are rather low, the GAMT activity in skeletal muscle was calculated to have the potential to synthesize all Cr needed in this tissue (149). The kidneys filter out most of the creatinine and dispose of it in the urine.Because the muscle mass in the body is relatively constant from day to day, the creatinine production normally remains essentially unchanged on a daily basis.Why is it important to check blood creatinine levels? Melatonin functions by inhibiting the synthesis and secretion of other neurotransmitters such as dopamine and GABA.
Reaction with an amino acid liberates cysteinylglycine and generates a g-glutamyl-amino acid which is transported into the cell and hydrolyzed to release the amino acid.
The coronary artery vasodilator, nitroglycerin, acts to increase intracellular release of EDRF and thus of cGMP. Oral Cr ingestion has also been shown to increase athletic performance, and it therefore comes as no surprise that Cr is currently used by many athletes as a performance-boosting supplement.
The two mitochondrial CK isoforms, ubiquitous Mi-CK and sarcomeric Mi-CK, are located in the mitochondrial intermembrane space and form both homodimeric and homooctameric molecules that are readily interconvertible. Cr exported from the liver and transported through the blood may then be taken up by the Cr-requiring tissues. The muscular Cr and PCr are nonenzymatically converted at an almost steady rate (?2% of total Cr per day) to creatinine (Crn), which diffuses out of the cells and is excreted by the kidneys into the urine. Furthermore, AGAT activity was detected in heart, lung, spleen, muscle, brain, testis, and thymus, and it has been estimated that the total amount of AGAT in these tissues approaches that found in kidney and pancreas (769,1055). Finally, feeding of rats and mice with 3-guanidinopropionic acid (GPA), a competitive inhibitor of Cr entry into cells, progressively decreased the concentrations of Cr and PCr in heart and skeletal muscle but had only little influence on the Cr and PCr contents of brain (372).
Glutamate is released as 5-oxoproline and the cysteinylglycine is cleaved to its component amino acids. Some data suggest that Cr and creatinine (Crn) may act as precursors of food mutagens and uremic toxins. All CK isoenzymes catalyze the reversible transfer of the ?-phosphate group of ATP to the guanidino group of Cr to yield ADP and PCr (Fig.1). According to this hypothesis, transport of high-energy phosphates between sites of ATP production and ATP consumption is achieved mainly (but not exclusively) by PCr and Cr.
Although AGAT is absent from human placenta, the decidua of pregnant females displayed the highest specific AGAT activity of all rat tissues examined (1077), implying a major involvement of this tissue in Cr biosynthesis during early stages of development.
One possible explanation is that the brain contains its own Cr-synthesizing machinery (171). Regeneration of GSH requires an ATP-dependent conversion of 5-oxoproline to glutamate and then the 2 additional moles of ATP that are required during the normal generation of GSH. Finally, the recent identification, purification, and cloning of many of the enzymes involved in Cr metabolism have just opened the door to a wide variety of biochemical, physiological, as well as clinical investigations and applications.
Whereas for the buffer function, no Mi-CK isoenzyme is required, Mi-CK may be a prerequisite for efficient transport of high-energy phosphates, especially if diffusion of adenine nucleotides across the outer mitochondrial membrane were limited (see sect. In line with this conclusion, maternofetal transport of Cr was demonstrated in the rat (157). To conclude, the detailed contribution of the various tissues of the body to total Cr biosynthesis as well as the relevance of guanidinoacetate and Cr transport between the tissues are still rather unclear; this is due both to a lack of thorough investigations and to the pronounced species differences observed so far.
Elevated creatinine level signifies impaired kidney function or kidney disease.As the kidneys become impaired for any reason, the creatinine level in the blood will rise due to poor clearance of creatinine by the kidneys. Abnormally high levels of creatinine thus warn of possible malfunction or failure of the kidneys.
It is for this reason that standard blood tests routinely check the amount of creatinine in the blood.A more precise measure of the kidney function can be estimated by calculating how much creatinine is cleared from the body by the kidneys. This is referred to as creatinine clearance and it estimates the rate of filtration by kidneys (glomerular filtration rate, or GFR). It can be calculated (estimated) by a formula using serum (blood) creatinine level, patient's weight, and age. Creatinine clearance can also be more directly measured by collecting a 24-hour urine sample and then drawing a blood sample. The BUN-to-creatinine ratio generally provides more precise information about kidney function and its possible underlying cause compared with creatinine level alone.
BUN also increases with dehydration.Recently, elevated creatinine levels in infants were associated with bacteremia while elevated levels in adult males have been linked to incresed risk of prostate cancer.

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