Urine citric acid

Tartaric acid and tartrates are poorly absorbed from the intestine. Their metaboHsm is different from that of citric acid in that tartaric acid is only slightly oxidized. The acid that is absorbed is excreted unchanged in the urine. So far as is known, all nutritional and physiological investigations have been made with the dextrorotatory enantiomer. 

Citric acid occurs widely in the plant and animal kingdoms (12). It is found most abundantiy in the fmits of the citms species, but is also present as the free acid or as a salt in the fmit, seeds, or juices of a wide variety of flowers and plants. The citrate ion occurs in all animal tissues and fluids (12). The total ckculating citric acid in the semm of humans is approximately 1 mg/kg body weight. Normal daily excretion in human urine is 0.2—1.0 g. This natural occurrence of citric acid is described in Table 7. 

Marnela et al. [57] used an amino acid analyzer using fluorescence detection to determine penicillamine in urine. Urine is analyzed on a Kontron Chromakon 500 amino acid analyzer containing a column (20 cm x 3.2 mm) of AS70 resin in the Li (I) form. Buffers containing LiOH, citric acid, methanol, HC1, and Brij 35 at pH 2.60, 3.20, and 3.60 are used as mobile phases (0.4 mL/h). The fluorescence reagent is prepared by the method of Benson and Hare. Detection is at 450 nm (excitation at 350 nm). The analyte response is linear from 0.025 to 10 mM, with a limit of detection of 25 pM. 

Bergstrom et al. [63] used HPLC for determination of penicillamine in body fluids. Proteins were precipitated from plasma and hemolyzed blood with trichloroacetic acid and metaphosphoric acid, respectively, and, after centrifugation, the supernatant solution was injected into the HPLC system via a 20-pL loop valve. Urine samples were directly injected after dilution with 0.4 M citric acid. Two columns (5 cm x 0.41 cm and 30 cm x 0.41 cm) packed with Zipax SCX (30 pm) were used as the guard and analytical columns, respectively. The mobile phase (2.5 mL/min) was deoxygenated 0.03 M citric acid-0.01 M Na2HP04 buffer, and use was made of an electrochemical detector equipped with a three-electrode thin-layer cell. The method was selective and sensitive for mercapto-compounds. Recoveries of penicillamine averaged 101% from plasma and 107% from urine, with coefficients of variation equal to 3.68 and 4.25%, respectively. The limits of detection for penicillamine were 0.5 pm and 3 pm in plasma and in urine, respectively. This method is selective and sensitive for sulfhydryl compounds. 

Tin metabolic acidosis (p. 652) there is an increase in glutamine processing by the kidneys. Not all the excess NH4 thus produced is released into the bloodstream or converted to urea some is excreted directly into the urine. In the kidney, the NH% forms salts with metabolic acids, facilitating their removal in the urine. Bicarbonate produced by the decarboxylation of a-lcetoglutarate in the citric acid cycle can also serve as a buffer in blood plasma. Taken together, these effects of glutamine metabolism in the kidney tend to counteract acidosis. ... 

In ureotelic organisms, the ammonia deposited in the mitochondria of hepatocytes is converted to urea in the urea cycle. This pathway was discovered in 1932 by Hans Krebs (who later also discovered the citric acid cycle) and a medical student associate, Kurt Henseleit. Urea production occurs almost exclusively in the liver and is the fate of most of the ammonia channeled there. The urea passes into the bloodstream and thus to the kidneys and is excreted into the urine. The production of urea now becomes the focus of our discussion. 

The urea cycle Urea is synthesized in the liver by the urea cycle. It is then secreted into the bloodstream and taken up by the kidneys for excretion in the urine. The urea cycle was the first cyclic metabolic pathway to be discovered by Hans Krebs and Kurt Henseleit in 1932,5 years before Krebs discovered the citric acid cycle (see Topic LI). The overall reaction of the pathway is ... 

Pathological urine A add 4 g glucose, 2 mL acetone and 2 g citric acid to 500 mL water... 

Citric acid is used in effervescing mixtures and granules. Formulations that contain citric acid are used in the management of dry mouth and to dissolve renal calculi, alkalinize the urine, and prevent encrustation of urinary catheters. Citric acid is also an ingredient of citrated anticoagulant solutions. 

Urine can turn dark in color in the first 24 hours after parenteral iron injection. The reddish-brown color, which has been observed after the intramuscular injection of iron sorbitol-citric acid complex (SED-8, 515), is due to urinary excretion of part of the iron compound. It has to be distinguished from the black discoloration that may develop if urine of patients who have received iron-sorbitex is allowed to stand, assumed to be due to production of iron sulfide by bacterial growth. Phenomena of this kind are unhkely to occur after the... 

Urine and bile analyzed on AE column (ES-502N 7C) with citric acid (15 mmol L , pH 2) as a mobile phase liver supernatants, plasma and red blood cells lysates on gel filtration column (GS 220 HQ) with ammonium acetate buffer (50 mmol L pH 6.5) on-line ICP-MS... 

Reduction of urine acidity can be accomplished by the administration of sodium bicarbonate or Shohl s solution (40 g citric acid and 98 g sodium citrate per liter). With the former, 2 to 6 g/day is given in equally divided doses at 6- to 8-hour intervals. A dose of 20 to 60 mL of ShohTs solution per day, given in three or four divided doses, provides an equivalent amount of alkali. If use of a sodium salt is contraindicated, potassium citrate may be used instead. 

Fates of tyrosine. Tyrosine can be degraded by oxidative processes to ace-toacetate and fumarate which enter the energy generating pathways of the citric acid cycle to produce ATP as indicated in Figure 38-2. Tyrosine can be further metabolized to produce various neurotransmitters such as dopamine, epinephrine, and norepinephrine. Hydroxylation of tyrosine by tyrosine hydroxylase produces dihydroxyphenylalanine (DORA). This enzyme, like phenylalanine hydroxylase, requires molecular oxygen and telrahydrobiopterin. As is the case for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to perturbations in dihydropteridine reductase or the biopterin synthesis pathway, anyone of which could lead to interruption of tyrosine hydroxylation, an increase in tyrosine levels, and an increase in transamination of tyrosine to form its cognate a-keto acid, para-hydroxyphenylpyruvate, which also would appear in urine as a contributor to phenylketonuria. 

Historical Development. Citric acid was the first of these acids to be identified in blood and urine. A few studies were later concerned with a-ketoglutaric and succinic acids in these biological fluids, until the development of chromatographic techniques allowed the determination of all acids of the tricarboxylic acid cycle, except the unstable ones (oxa-losuccinic and oxalacetic acids). Besides the chromatographic techniques, new enzymatic and fluorimetric methods have been described for some of these acids, including oxalacetic acid. 

Citric Acid. Thunberg (T21) has summarized the steps which led to the identification of citric acid in urine. Found in lemon juice by Scheele in 1784, citric acid was considered a typical plant acid until its presence was shown in milk in 1888. Classified among the normal metabolites by Thunberg since 1910, this acid was found first in animal urine after administration of citrate, then in normal human urine by Amberg and McClure (A6). Later on, it was found also in normal human plasma by Benni et al. (B9). 

Citric acid forms a constant spot on the chromatograms of organic acids of plasma or urine obtained by the general technique summarized ear-her. This spot is, however, badly separated from the starting point, due to interference by residual quantities of phosphate and sulfate. Such chromatographic techniques are therefore not suitable for estimating the citric acid content of blood or urine. 

Influence of age. The influence of age on the blood citrate level has already been discussed. Excretion of acids of the citric acid cycle, as well as of other organic acids, has been studied by Zweimiiller and McCance (Z6, Z7) in urine passed before and shortly after birth the acids of the tricarboxylic acid cycle are already present in such urine samples. 

The question arises whether or not the changes in elimination due to the variations in the acid-base balance affect citric acid specifically. Melius and Lipton (M18) thus found that, in experimental alkalosis produced in rats after injection of bicarbonate, only about 50 % of the increase of urinary organic acids is due to citrate. Evans et al. (E8), who did not find the same result in man after bicarbonate administration, state also that citrate represents less than 50 % of the inerease of organic acids in urine produced in man by hyperventilation. 

A few facts concerning pathological modifications of citric acid in blood or urine will be discussed before considering these diseases. 

Extensive work has been done on modifications of citric acid metabolism, which appear especially interesting because of the interrelationship between citrate and calcium in blood and urine, and of the numerous factors which are known to affect the citrate level in normal subjects. 

The elimination of citric acid was shown by many workers to be decreased in diabetic patients (B24, K18, 08, 012) thus, Otto (08) found that the amount of citrate excreted in urine during diabetic coma is only 2-10 % of the normal values. It is not established whether this hypocitraturia is related to a metabolic abnormaUty, due to the disease itself, or to the acidosis, or even to a renal failure during coma (08) it appears, however, that the magnitude in the decrease of urinary citrate is not related to the severity of the acidosis (08). One must add that, if the results of Rechenberger and Benndorf (R4) concerning the decrease of blood citrate levels are confirmed, diabetic patients present a simultaneous decrease in blood and urine citrate analogous to that found by Nordmann et al. (N17) during acute renal insuflBciency. 

There are no studies that indicate that metabolism of ammonia differs between children and adults. Ammonia is eliminated from the body mainly by processing through the urea cycle in the liver, and urea is then eliminated in the urine and feces. The urea cycle is fully functional in infants at birth therefore, it is not expected that infants or children are at greater risk of hyperammonemia. Neurotoxicity resulting from h q)erammonemia involves alteration of levels of some components of the citric acid cycle, which leads to depletion of ATP, and starvation of brain cells, and depletion of glutamate, a precursor to the neurotransmitter y-aminobutyrate (GABA). It is not expected that children are more susceptible than adults to ATP depletion via this mechanism. 

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