Citric acid in blood

Nordmann et al. (N17) have recently found 1.54 0.09 mg% citric acid in blood plasma from 46 normal human subjects. This plasma level does not diflFer significantly in males and females (R4), but depends on the age of the subject. Rechenberger and Benndorf (R4) have shown, indeed, that the plasma citrate level falls with increasing age (being, for instance, 1.70 0.28 mg% between 11 and 20 years and 1.15 0.24 mg% after 60 years). 

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

An increase of citric acid in blood during liver failure has been found by many Scandinavian authors these studies have been reviewed by Hagelstam (H2) and Welin (WIO). The citric add content of the plasma is elevated during hepatitis, but not in patients vdth extrahepatic... 

Wolcott GH, Boyer PD (1948) A colorimetric method for the determination of citric acid in blood and plasma. J Biol Chem 172 729-736... 

Nordbo R, Scherstern B (1931) Determination of citric acid in blood by Thunberg s method and by the pentabromoacetone method. Scand Arch Physiol 63 124-132 Ostberg O (1934) Determination of citric acid in blood semm by Thunberg s method. Scand Arch Physiol 68 265-274... 

Human blood plasma, citric acid in, 6 632t Human chorionic gonadotropin (Chorulon), spawning aid for aquaculture in U.S., 3 214t... 

Human transferrin, yeast-derived, 26 486 Human whole blood, citric acid in, 6 632t Humectants, 12 32 in food, 12 65... 

The molar ratio of a-ketoglutaric acid to citric acid in whole blood is about 1 9.3 (G9). 

As compared to the numerous studies concerning alteration of the acids of the citric acid cycle and metabolically associated acids in blood, there have been only a few investigations on changes in the urinary... 

Platelet Adhesion. Venous blood from healthy human volunteers, who did not receive any agents which affect platelet function, was collected with a vacuum syringe containing 5 % citric acid. The blood was centrifuged at 800 rpm for 10 min at 25 C, and the platelet-rich plasma (PRP) was withdrawn with a polyethylene pipette and placed in clean vials at room temperature. A portion of PRP was diluted by adding PBS and centrifuged at 1800 rpm for 10 min to prepare platelet pellets. The residue of the blood was further centrifuged at 3,000 rpm for 10 min to obtain platelet-poor plasma (PPP). The platelet count was determined with Coulter Counter (Type 4) and adjusted to have 150,000 platelets in 1... 

Citric acid is a metabolic product of all respiring tissue. The skeleton constitutes an important source of circulating citric acid. The injections of labeled citric acid demonstrate that the turnover of citric acid in the blood is rapid, yet the levels of citric acid in the blood are constant however, the factors that determine citric acid homeostasis are not known. The amount of calcium in the circulating blood is likely to play an important role in regulating blood levels of citric acid. The plasma concentrations of citrate and calcium correlate consistently in the nephrecto-mized rat. Nephrectomy markedly elevates plasma citrate and causes a corresponding rise in the diffusible nonionized fraction of plasma calcium. Parathyroid extract produces a decrease in the plasma citric response to nephrectomy, and parathyroidectomy is much more effective in male than in female animals. 

Virtually no other quantitative data on concentrations of organic acids in blood from normal healthy individuals have been reported, although Chalmers (1974) recorded the citric acid concentration in blood plasma as determined by gas-liquid chromatography, as 2.6 mg (100 ml)" in agreement with data obtained by enzymic methods. Some other data on individual acids have been obtained in studies of specific disease states and these are recorded in the appropriate sections of Part III. 

Medical Uses. Citric acid and citrate salts are used to buffer a wide range of pharmaceuticals at their optimum pH for stabiUty and effectiveness (65—74). Effervescent formulations use citric acid and bicarbonate to provide rapid dissolution of active ingredients and improve palatabiUty. Citrates are used to chelate trace metal ions, preventing degradation of ingredients. Citrates are used to prevent the coagulation of both human and animal blood in plasma and blood fractionation. Calcium and ferric ammonium citrates are used in mineral supplements. 

In extrahepatic tissues, acetoacetate is activated to acetoacetyl-CoA by succinyl-CoA-acetoacetate CoA transferase. CoA is transferred from succinyl-CoA to form acetoacetyl-CoA (Figure 22-8). The acetoacetyl-CoA is split to acetyl-CoA by thiolase and oxidized in the citric acid cycle. If the blood level is raised, oxidation of ketone bodies increases until, at a concentration of approximately 12 mmol/L, they saturate the oxidative machinery. When this occurs, a large proportion of the oxygen consumption may be accounted for by the oxidation of ketone bodies. 

Contant G., Gouault-Heilmann M., Martinoli J. L. Heparin inactivation during blood storage Its prevention by blood collection in citric acid, theophylline, adenosine, dipyridamole—CTAD mixture. Thromb Res 1983 31,365-74. 

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. 

Citrated blood is diluted 1 10 with enzyme buffer solution, and preservative is added (H19). The buffer is prepared by dissolving 0.2 g of Clarase (Fisher Scientific Co., New York) in 100 ml citrate buffer (5 g potassium citrate monohydrate and 1 g citric acid monohydrate in 1000 ml distilled water, pH 5.6). The solution is incubated for 3 days at 37°. After incubation, it is autoclaved 15 minutes to stop enzymatic action and coagulate proteins. It is filtered, and 1.0, 1.5, and 2.0 ml of the supernatant is added to individual flasks and assayed. Control flasks are included to estimate pantothenic acid contamination of the enzyme. 

O Ketoacidosis is a dangerous condition that is characterized by the acidification of the blood and an acetone odour on the breath. The condition occurs when levels of oxaloacetic acid for the citric acid cycle are low. This leads to a buildup of acetyl CoA molecules, which the liver metabolizes to produce acidic ketone bodies. Since carbohydrates are the main source of oxaloacetic acid in the body, high-protein, low-carbohydrate diets have been linked to ketoacidosis. 

In a festing state, the liver produces more acetyl CoA from p oxidation than is used in the citric acid cycle. Much of the acetyl CoA is used to synthesize ketone bodies (essentially two acetyl CoA groups linked tc ether) that are released into the blood for other tissues. 

Pitfalls associated with metabolic screening are numerous. They can result from proximal tubulopathy, causing a reduction in blood lactate and an increase in urinary lactate from diabetes mellitus, hampering entry of pyruvate into the citric acid cycle from tissue-specific involvement or partial deficiency, which may barely alter the redox status in plasma. When metabolic tests are negative, respiratory chain deficiency may be misdiagnosed. 

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. ... 

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