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Study Guide: Uric Acid: Biochemistry, Physiology, and Clinical Significance

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Uric Acid: Biochemistry, Physiology, and Clinical Significance Study Guide

Biochemical Properties and Structure

Uric acid, a key metabolic byproduct, is characterized as a heterocyclic compound comprising carbon, nitrogen, oxygen, and hydrogen atoms.

Answer: True

Explanation: The molecular structure of uric acid is that of a heterocyclic compound containing carbon, nitrogen, oxygen, and hydrogen. Its chemical formula is C5H4N4O3.

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Uric acid exhibits lactam-lactim tautomerism and predominantly crystallizes in the lactam form, which is recognized as its most stable tautomeric configuration.

Answer: True

Explanation: Uric acid can exist in two tautomeric forms, lactam and lactim, due to proton and double bond migration. It crystallizes in the lactam form, which computational studies confirm as the most stable.

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Uric acid is a simple organic compound containing only carbon, hydrogen, and nitrogen.

Answer: False

Explanation: Uric acid is a heterocyclic compound composed of carbon, nitrogen, oxygen, and hydrogen. Its chemical formula is C5H4N4O3.

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Uric acid is a monoprotic acid with a single pKa value, indicating that only one proton can be readily removed.

Answer: False

Explanation: Uric acid is a diprotic acid, possessing two pKa values (approximately 5.4 and 10.3), meaning it can donate two protons under different conditions.

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Uric acid and its alkali metal salts exhibit high water solubility, particularly in cold aqueous solutions.

Answer: False

Explanation: Uric acid and its alkali metal salts have generally low water solubility. While solubility increases with temperature, they are less soluble in cold water compared to hot water.

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Urate salts demonstrate significant solubility in ethanol, comparable to their solubility in water.

Answer: False

Explanation: Urate salts exhibit very low or negligible solubility in ethanol. Their solubility in ethanol-water mixtures falls between the values for pure ethanol and pure water.

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What is the molecular formula for uric acid?

Answer: C5H4N4O3

Explanation: The chemical formula for uric acid is C5H4N4O3. This reflects its composition of five carbon atoms, four nitrogen atoms, four hydrogen atoms, and three oxygen atoms.

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What type of chemical phenomenon does uric acid exhibit regarding its structure, allowing it to exist in two forms differing by proton and double bond position?

Answer: Lactam-lactim tautomerism

Explanation: Uric acid exhibits lactam-lactim tautomerism, a form of isomerism where a molecule can exist in two forms that differ by the position of a proton and a double bond. It crystallizes in the lactam form, which is the most stable tautomer.

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What is the predominant ionic species of uric acid in aqueous solution at physiological pH (approximately 7.4)?

Answer: Hydrogen urate ion

Explanation: At physiological pH of approximately 7.4, uric acid predominantly exists as the hydrogen urate ion (urate anion), due to its first pKa value being below this pH.

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How does the water solubility of uric acid and its salts generally behave in relation to temperature?

Answer: They are more soluble in hot water than in cold water.

Explanation: The solubility of uric acid and its alkali metal salts increases with temperature; they are generally more soluble in hot water than in cold water.

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Discovery and Synthesis

Carl Wilhelm Scheele is credited with the initial isolation of uric acid in 1776, obtaining it from kidney stones.

Answer: True

Explanation: Carl Wilhelm Scheele, a Swedish chemist, first isolated uric acid in 1776. His isolation was achieved by analyzing kidney stones.

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The initial laboratory synthesis of uric acid was achieved by Ivan Horbaczewski in 1882 through the fusion of urea and glycine.

Answer: True

Explanation: Ivan Horbaczewski, a Ukrainian chemist, first synthesized uric acid in 1882 via a process involving the melting of urea with glycine.

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Carl Wilhelm Scheele discovered uric acid in 1776 by isolating it from human blood plasma.

Answer: False

Explanation: Carl Wilhelm Scheele first isolated uric acid in 1776, but his source material was kidney stones, not blood plasma.

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Who first isolated uric acid, and from what substance was it obtained?

Answer: Carl Wilhelm Scheele, from kidney stones

Explanation: Carl Wilhelm Scheele, a Swedish chemist, first isolated uric acid in 1776. His isolation was achieved by analyzing kidney stones.

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Metabolism and Enzymology

Molybdenum is an essential component within the active site of xanthine oxidase, playing a critical role in its catalytic function.

Answer: True

Explanation: Molybdenum is a crucial cofactor integrated into the active site of the xanthine oxidase enzyme, enabling its catalytic activity in the metabolism of purines.

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The enzyme xanthine oxidase catalyzes the conversion of uric acid into hypoxanthine and xanthine.

Answer: False

Explanation: Xanthine oxidase catalyzes the final steps in purine catabolism, converting hypoxanthine to xanthine and then xanthine to uric acid. It does not break down uric acid.

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Which enzyme is responsible for catalyzing the conversion of hypoxanthine and xanthine into uric acid?

Answer: Xanthine oxidase

Explanation: The enzyme xanthine oxidase (XO) catalyzes the final two steps of purine catabolism: the conversion of hypoxanthine to xanthine, and xanthine to uric acid.

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What is the primary role of molybdenum within the xanthine oxidase enzyme?

Answer: It is essential for the enzyme's catalytic activity in its active site.

Explanation: Molybdenum, integrated into the cofactor of xanthine oxidase, is critical for the enzyme's catalytic function, participating directly in the oxidation reactions of purine substrates.

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Physiology, Excretion, and Antioxidant Roles

In humans, the hydrogen urate ion contributes substantially, accounting for over half of the total antioxidant capacity present in blood plasma.

Answer: True

Explanation: The hydrogen urate ion is a significant endogenous antioxidant in human blood plasma, contributing more than 50% of its overall antioxidant capacity.

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The renal system is responsible for the elimination of approximately 70% of the body's daily uric acid load in humans.

Answer: True

Explanation: The kidneys play a primary role in uric acid homeostasis, excreting roughly 70% of the daily production through urine. Impaired renal excretion is a common cause of hyperuricemia.

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Uric acid is typically released or its production is favored under conditions of high oxygen saturation.

Answer: False

Explanation: Uric acid production and release are favored under hypoxic conditions, which are characterized by reduced oxygen availability, not high oxygen saturation.

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Normal uric acid levels in human blood are typically higher for women than for men.

Answer: False

Explanation: Generally, normal uric acid concentrations in human blood are higher in men than in women, although levels can vary based on age and physiological status.

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The daily excretion of uric acid in human urine is significantly higher than that of urea.

Answer: False

Explanation: The daily excretion of uric acid in human urine is considerably lower than that of urea. Uric acid excretion is approximately 270-360 mg daily, whereas urea excretion is much higher.

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Under which physiological conditions is uric acid typically released or its production favored?

Answer: Hypoxic conditions

Explanation: Uric acid production and release are favored under hypoxic conditions, which are characterized by reduced oxygen availability, impacting cellular redox states.

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What functional similarity has been proposed between uric acid in higher primates and ascorbic acid (Vitamin C)?

Answer: Both function as strong reducing agents and potent antioxidants.

Explanation: The loss of uricase in higher primates suggests that urate may have evolved to serve as a potent antioxidant, similar to ascorbic acid, due to its strong reducing capabilities.

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What proportion of the antioxidant capacity of human blood plasma is attributed to the hydrogen urate ion?

Answer: Over half

Explanation: The hydrogen urate ion is a significant contributor to the antioxidant capacity of human blood plasma, accounting for more than 50% of this function.

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How is uric acid primarily eliminated from the body in humans?

Answer: Through the kidneys into urine

Explanation: The primary route for uric acid elimination in humans is through the kidneys, where approximately 70% of the daily load is excreted in the urine.

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What is pseudohypoxia in the context of uric acid metabolism?

Answer: A disrupted NADH/NAD+ ratio leading to elevated uric acid.

Explanation: Pseudohypoxia refers to a condition where cellular redox state, specifically a disrupted NADH/NAD+ ratio, mimics the effects of low oxygen, leading to increased uric acid production.

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How do gut bacteria metabolize uric acid in humans?

Answer: Into xanthine, lactate, acetate, and butyrate.

Explanation: A portion of uric acid is metabolized by anaerobic gut bacteria into various compounds, including xanthine, lactate, acetate, and butyrate.

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Clinical Manifestations and Pathophysiology

The limited aqueous solubility of uric acid is a significant factor contributing to the pathogenesis of gout, as it can precipitate as crystals within joints.

Answer: True

Explanation: The low water solubility of uric acid is a primary etiological factor in gout, leading to the deposition of urate crystals in synovial joints and other tissues.

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Hyperuricemia, characterized by elevated serum uric acid levels, is associated with various components of the metabolic syndrome in both adult and pediatric populations.

Answer: True

Explanation: Elevated blood uric acid levels (hyperuricemia) have been observed to correlate with key features of metabolic syndrome, including hypertension, dyslipidemia, insulin resistance, and central obesity, across different age groups.

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Uric acid crystals can potentially act as 'seed crystals,' thereby promoting the formation of calcium oxalate stones within the renal system.

Answer: True

Explanation: The presence of uric acid crystals can facilitate the nucleation and growth of calcium oxalate stones, acting as a nidus for their formation in the kidneys.

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Myogenic hyperuricemia is characterized by high ATP reserves in muscle cells, leading to decreased purine nucleotide cycle activity.

Answer: False

Explanation: Myogenic hyperuricemia is associated with low ATP reserves in muscle cells, which activates the purine nucleotide cycle and leads to increased purine breakdown products, including uric acid.

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Gout is a condition characterized by low uric acid levels, causing urate crystals to precipitate in tissues.

Answer: False

Explanation: Gout is fundamentally caused by excess uric acid in the blood (hyperuricemia), leading to the precipitation of monosodium urate crystals in joints and other tissues.

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Which condition is directly associated with high blood concentrations of uric acid (hyperuricemia) due to crystal precipitation?

Answer: Gout

Explanation: Gout is a direct clinical manifestation of hyperuricemia, resulting from the deposition of monosodium urate crystals in joints and soft tissues.

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Myogenic hyperuricemia is characterized by:

Answer: Low ATP reserves in muscle cells and active purine cycle.

Explanation: Myogenic hyperuricemia arises from low intracellular ATP levels in muscle cells, which stimulates the purine nucleotide cycle and leads to increased production of uric acid precursors.

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What metabolic complication associated with certain cancers or chemotherapy leads to elevated uric acid levels due to the release of cellular contents?

Answer: Tumor lysis syndrome

Explanation: Tumor lysis syndrome is a condition resulting from the rapid breakdown of cancer cells, releasing intracellular components including purines, which leads to a significant increase in uric acid production.

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Gout is primarily caused by:

Answer: Excess uric acid in the blood (hyperuricemia) leading to crystal precipitation.

Explanation: Gout is a form of inflammatory arthritis resulting from hyperuricemia, where excess uric acid crystallizes and deposits in joints, triggering inflammation.

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What is a potential cause for low uric acid levels (hypouricemia)?

Answer: Use of sevelamer medication

Explanation: The medication sevelamer, used in managing chronic kidney disease, has been shown to significantly reduce serum uric acid levels, potentially leading to hypouricemia.

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Studies suggest a correlation between lower serum uric acid levels and which neurological condition?

Answer: Multiple sclerosis

Explanation: Research indicates that individuals diagnosed with multiple sclerosis tend to have significantly lower serum uric acid levels compared to healthy controls.

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Evolutionary and Comparative Biology

The evolutionary loss of the uricase enzyme in higher primates mirrors the loss of Vitamin C synthesis, suggesting that urate may serve an antioxidant function.

Answer: True

Explanation: The absence of functional uricase in higher primates, analogous to the loss of ascorbic acid synthesis, has led to the hypothesis that urate may provide a compensatory antioxidant capacity.

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In the majority of mammalian species, the enzyme uricase further oxidizes uric acid into allantoin.

Answer: True

Explanation: The enzyme uricase is responsible for the further oxidation of uric acid to allantoin in most mammals. Humans, however, lack a functional uricase enzyme.

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In humans, the enzyme uricase converts uric acid into allantoin, mirroring the metabolic pathway found in most other mammals.

Answer: False

Explanation: Humans lack the functional uricase enzyme and therefore cannot convert uric acid into allantoin. This metabolic pathway is present in most other mammals.

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Dalmatian dogs, unlike most mammals, possess an efficient uricase enzyme that converts uric acid into allantoin.

Answer: False

Explanation: Dalmatian dogs are genetically distinct in their uric acid metabolism; they lack the efficient uricase enzyme and excrete uric acid directly in urine, rather than converting it to allantoin.

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In birds and reptiles, uric acid is the final product of purine metabolism and is excreted dissolved in water.

Answer: False

Explanation: While uric acid is the final product of purine metabolism in birds and reptiles, it is excreted as a semi-solid or dry paste to conserve water, not dissolved in water.

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In most mammals, what is the final metabolic product derived from uric acid?

Answer: Allantoin

Explanation: In most mammals, the enzyme uricase catalyzes the conversion of uric acid into allantoin, which is a more water-soluble compound.

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What metabolic characteristic regarding uric acid excretion is unique to Dalmatian dogs compared to most other mammals?

Answer: They excrete uric acid directly in their urine due to a genetic defect.

Explanation: Dalmatian dogs possess a specific genetic defect affecting uric acid transport in the liver and kidneys, causing them to excrete uric acid directly into urine rather than metabolizing it to allantoin.

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In which animal groups is uric acid the final product of purine metabolism and typically excreted as a dry mass?

Answer: Birds, reptiles, and certain desert mammals

Explanation: Birds, reptiles, and certain desert-dwelling mammals excrete uric acid as the terminal product of purine metabolism, often in a dry or semi-solid form to conserve water.

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Genetic, Pharmacological, and Dietary Factors

The SLC2A9 gene encodes the GLUT9 transporter protein, which is implicated in the transport of both uric acid and fructose across cell membranes.

Answer: True

Explanation: The SLC2A9 gene provides the instructions for making the GLUT9 protein, a transporter known to facilitate the movement of both uric acid and fructose, and its variants are associated with serum urate levels.

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Dietary consumption of purine-rich foods, such as organ meats and certain seafood, is associated with an elevated risk of developing gout.

Answer: True

Explanation: Ingestion of foods high in purines, including organ meats and specific types of seafood, is recognized as a dietary factor that can increase the risk of gout due to elevated serum uric acid levels.

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Allopurinol is a therapeutic agent that manages urate levels by inhibiting the activity of xanthine oxidase, thereby reducing the endogenous production of uric acid.

Answer: True

Explanation: Allopurinol functions as a xanthine oxidase inhibitor, effectively decreasing the synthesis of uric acid from its precursors, hypoxanthine and xanthine, thus serving as a treatment for hyperuricemia.

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Dietary factors such as meat and seafood are considered the primary contributors to high serum urate levels, surpassing the influence of genetics.

Answer: False

Explanation: While diet plays a role, genetic variations are considered a substantially greater contributor to high serum urate levels compared to dietary purine intake.

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Which factor is considered a greater contributor to elevated serum urate levels: dietary intake or genetic predisposition?

Answer: Genetic variation

Explanation: Genetic variations are recognized as having a substantially greater impact on determining an individual's serum urate levels compared to dietary factors alone.

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The SLC2A9 gene encodes which transporter protein known to transport both uric acid and fructose?

Answer: GLUT9

Explanation: The SLC2A9 gene encodes the GLUT9 transporter protein, which plays a role in the cellular uptake and transport of both uric acid and fructose.

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Which dietary components are mentioned as factors that can increase uric acid levels in the blood?

Answer: High-fructose corn syrup and sucrose

Explanation: Consumption of high-fructose corn syrup and sucrose is identified as a dietary factor that can contribute to elevated uric acid levels.

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How do thiazide diuretics typically affect blood uric acid levels?

Answer: They increase levels by interfering with kidney clearance.

Explanation: Thiazide diuretics can elevate blood uric acid levels by impairing the kidneys' ability to excrete uric acid, leading to reduced clearance.

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Which of the following foods is NOT typically considered a high-purine food that increases gout risk?

Answer: Moderate purine-rich vegetables

Explanation: Unlike organ meats and certain seafood, moderate consumption of purine-rich vegetables is not associated with an increased risk of gout.

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How does the medication allopurinol help manage uric acid levels?

Answer: By inhibiting xanthine oxidase, thus reducing uric acid production.

Explanation: Allopurinol functions as a xanthine oxidase inhibitor, which decreases the synthesis of uric acid from its precursors, thereby lowering serum urate levels.

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Miscellaneous Roles and Organisms

What specific role does uric acid fulfill in the marine polychaete worm *Platynereis dumerilii*?

Answer: It functions as a sexual pheromone.

Explanation: In the marine polychaete worm *Platynereis dumerilii*, uric acid serves as a sexual pheromone, influencing mating behavior.

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