Metabolism and Disposal of Urea, Creatinine and Uric Acid: MCQ

Multiple Choice Question on Metabolism and Disposal of  Urea, Creatinine, 

and Uric Acid

1) The urea molecule consists of two Nitrogens and one carbon atom. The first nitrogen atom is derived from the free ammonium ion and the second is from an amino acid. 

The amino acid that donates the second amino group for the formation of urea is................................

a) Arginine

b) Aspartate

 c) Glutamate

d) Ornithine

2) The free ammonium group  (NH4+) is derived from the following processes:

a) Oxidative deamination of Glutamine catalyzed by enzyme glutamate dehydrogenase
b) Deamidation of histidine catalyzed by the enzyme histidase
c) Deamidation of serine and threonine by a PLP requiring enzyme serine dehydratase
d) All of the above

3) The first step in the urea cycle is a condensation of CO2, ammonia, and ATP to form carbamoyl phosphate. 

The following are true regarding the formation of carbamoyl phosphate, Except:

a) The reaction is catalyzed by a rate-limiting enzyme carbamoyl phosphate synthase-I
b) The presence of N-acetyl glutamate inhibits the activity of the CPS I enzyme
c) Two molecules of ATP are required for this reaction
d) The reaction occurs in mitochondria

4) Which of the following amino acid: keto acid pair bridges the urea cycle with the tricarboxylic acid cycle for the maintenance of the nitrogen and amino acid pool?

a) Glutamate: Alpha-ketoglutarate
b) Aspartate: Oxaloacetate
c) Alanine: Pyruvate
d) None of the above

5) Four Adenosine triphosphate equivalents are required for the formation of urea in the urea cycle. 

Which of the following enzymes utilize the ATPs? 

a) Carbamoyl Phosphate synthase I
b) Ornithine Transcarbamoylase
c) Argininosuccinate synthase
d) Ariginosuccinase

6) The carbamoyl-phosphate is synthesized in the mitochondria and subsequently converted into citrulline. The remainder of the steps occurs in the cytosol requiring the transport of citrulline into the cytosol. The mitochondrial transporter is a.............................................

a) symport that co-transport arginine with ornithine
b) antiport that exchanges arginine with ornithine
c) symport that co-transport citrulline with ornithine
d) antiport that exchanges citrulline with ornithine

7) The deficiency of which of the following enzymes urea cycle results in impaired synthesis of urea, accumulation of ammonia (hyperammonemia), and orotic aciduria?

a) Carbamoyl Phosphate synthase I
b) Ornithine Transcarbamoylase
c) Argininosuccinate synthase
d) Ariginosuccinase

8) The deficiency of which of the following enzyme causes Citrullinemia- a condition with an accumulation of citrulline in the blood?

a) Carbamoyl Phosphate I
b) Ornithine Transcarbamoylase
c) Argininosuccinate synthase
d) Ariginosuccinase

9) Which of the following compound is administered to patients with urea cycle defects to remove ammonia?

a) Inulin
b) Phenylbutyrate
c) Arginine
d) Ornithine

10) The following conditions lead to the hyperammonemia
a) Chronic Liver Cirrhosis
b) GI bleeding
c) Deficiency of CPS I
d) All of the above

11) The creatine synthesis begins in the kidney and is completed liver and requires three different amino acids for its formation. The creatine undergoes phosphorylation to form creatine phosphate in various tissue. 

The following amino acids are required for its synthesis EXCEPT:

a) Alanine
b) Arginine
c) Glycine
d) Methionine

12) The interconversion of creatine and creatine phosphate is catalyzed by an enzyme creatine kinase. Creatine kinase has three different isoenzymes.  

Which of the following isoenzyme is present in heart tissue that is elevated in myocardial infarction?

a) CK-MM
b) CK-MB
c) CK-BB
d) None of the above

13) The interconversion of creatine and creatine phosphate is catalyzed by an enzyme creatine kinase. Creatine kinase has three different isoenzymes.  

Which of the following isoenzyme is elevated in skeletal muscle atrophy?

a) CK-MM
b) CK-MB
c) CK-BB
d) None of the above

14) Creatinine is a compound formed by a spontaneous cyclization of creatine phosphate in the brain and muscles. 

The following statement is true for creatinine, Except:

a) One to two percent of Creatine phosphate is irreversibly converted to creatinine
b) The concentration of creatinine is fairly constant and relative to body muscle mass
c) Creatinine is freely filtered through the glomerular membrane
d) Creatinine is not secreted by kidney tubules

15) Creatinine clearance is used for............................................

a) estimation of renal blood flow
b) estimation of glomerular filtration rate

c) evaluation of nephrolithiasis
d) None of the above

16) Uric acid is the excretory end product of purine metabolism. 

Which of the following condition lead to the increased production of uric acid?

a) Hypoxanthine- Guanosine phosphoribosyltransferase
b) Increased lactate levels and chronic alcoholism
c) Acute and Chronic Renal Disease
d) All of the above

17) Which of the following amino acids have an important role in the transport of amino groups from peripheral tissues to the liver?

a) Serine
b) Methionine
c) Glutamine
d) Arginine

18) The following metabolites are excreted via urine to maintain the nitrogen balance, Except:

a) Amino acids

b) Creatinine

c) Urea

d) Ammonia

19) In citrullinemia- a problem in the urea cycle, which of the following pathway is suppressed?

a) Glycolysis

b) Glycogenesis

c) Glycogenolysis

d) Gluconeogenesis

20) The Urea cycle is the most energy-efficient cycle. It requires ATP for the continuation of the cycle. 

Identify an intermediate that utilizes ATP for the formation:

a) Arginine

b) Ornithine

c) Citrulline

d) Arginine succinate

21) Which of the following is the end product of purine metabolism in humans?

a) Xanthine

b) Uric acid

c) Urea

d) Allantoin

Multiple Choice Answers and Explanation:-
1-b) Aspartate

The second amino group for the formation of urea comes from aspartate, which is an amino acid that is synthesized in the liver. Aspartate is converted to oxaloacetate, which can then react with ammonia to form carbamoyl phosphate in the mitochondrial matrix. This carbamoyl phosphate can then enter the urea cycle and react with ornithine to form citrulline, as described in my previous response.
In summary, the second amino group for the formation of urea comes from the amino acid aspartate, which is converted to carbamoyl phosphate in the mitochondrial matrix and then enters the urea cycle.

2-d) All of the above

In the urea cycle, the ammonium ion (NH4+) is formed from the reaction of ammonia (NH3) with carbon dioxide (CO2) and ATP, which is catalyzed by the enzyme carbamoyl phosphate synthetase I (CPS I). This reaction occurs in the mitochondrial matrix of liver cells.
Deamination of amino acids releases free ammonia: Amino acids are the building blocks of proteins, and when they are broken down in the body, the amino group (-NH2) is removed from the amino acid and converted to ammonia (NH3). This reaction occurs mainly in the liver.

Glutamate dehydrogenase (GDH) is an enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate (also known as 2-oxoglutarate) and ammonia (NH3). GDH plays an important role in the metabolism of amino acids and the urea cycle.
Histidase, also known as histidine ammonia-lyase (HAL), is an enzyme that catalyzes the breakdown of the amino acid histidine to urocanic acid and ammonia. 

Serine dehydratase, also known as serine racemase, is an enzyme that catalyzes the conversion of serine to pyruvate, with the concomitant release of ammonia.

3- b) The presence of N-acetyl glutamate inhibits the activity of the CPS I enzyme

The first step in the urea cycle is the conversion of ammonia and carbon dioxide to carbamoyl phosphate, which is catalyzed by the enzyme carbamoyl phosphate synthetase I (CPS I).
The activity of CPSI is allosterically regulated by N-acetylglutamate (NAG), which is synthesized from acetyl-CoA and glutamate by the enzyme N-acetylglutamate synthase (NAGS). NAG is an allosteric activator of CPSI, and its binding to the enzyme enhances its activity. The levels of NAG are determined by the availability of its precursors, acetyl-CoA and glutamate. Thus, when there is an increase in the levels of ammonia or amino acids, the production of NAG is stimulated, leading to an increase in the activity of CPSI and the urea cycle.
The reaction requires the input of two molecules of ATP (adenosine triphosphate), which provide the energy necessary for the reaction to proceed. In the liver, CPSI is localized in the mitochondrial matrix, where it can access the ammonia that is generated during the catabolism of amino acids. T

4- b) Aspartate: Oxaloacetate

There are two keto acid pairs that bridge the urea cycle with the tricarboxylic acid (TCA) cycle, namely, aspartate-α-ketoglutarate and glutamate-oxaloacetate.
Aspartate-α-ketoglutarate pair: Aspartate is formed in the urea cycle from the condensation of carbamoyl phosphate and aspartate. Aspartate can then be transported out of the mitochondria and converted back into oxaloacetate by the action of the enzyme aspartate aminotransferase. The resulting α-ketoglutarate can enter the TCA cycle and undergo oxidative metabolism to generate energy.
Glutamate-oxaloacetate pair: Glutamate is formed in the urea cycle from the condensation of ammonia and α-ketoglutarate. Glutamate can then be transported out of the mitochondria and converted back into α-ketoglutarate by the action of the enzyme glutamate dehydrogenase. The resulting oxaloacetate can enter the TCA cycle and undergo oxidative metabolism to generate energy.

5-a) Carbamoyl Phosphate synthase I &c) Argininosuccinate synthase

CPSI (carbamoyl phosphate synthetase I): CPSI uses two molecules of ATP to convert ammonia and bicarbonate into carbamoyl phosphate, which is the first step in the urea cycle.
ASS (argininosuccinate synthase): ASS uses one molecule of ATP to catalyze the formation of argininosuccinate from citrulline and aspartate, which is the step that precedes the formation of arginine in the urea cycle.

6- d) Antiport that exchanges citrulline with ornithine

The mitochondrial transporter involved in the urea cycle is called the ornithine/citrulline transporter. This transporter facilitates the transport of ornithine, citrulline, and arginine across the mitochondrial membrane. Ornithine is transported into the mitochondria to initiate the urea cycle, while citrulline and arginine are exported out of the mitochondria and into the cytosol for further metabolism and elimination of nitrogen.
The ornithine/citrulline transporter is an antiporter, which means that it simultaneously transports two substrates in opposite directions. It exchanges ornithine for citrulline or vice versa, depending on the concentration gradient of the substrates across the mitochondrial membrane. 

7- b) Ornithine Transcarbamoylase

The enzyme deficiency that results in impaired synthesis of urea, accumulation of ammonia (hyperammonemia), and orotic aciduria is Ornithine Transcarbamylase (OTC) deficiency.
OTC is the enzyme responsible for catalyzing the reaction between carbamoyl phosphate and ornithine to form citrulline in the urea cycle. In the absence or deficiency of OTC, carbamoyl phosphate accumulates and is shunted towards alternative pathways, resulting in the accumulation of ammonia and the formation of orotic acid.
The accumulation of ammonia can lead to neurotoxicity and other adverse effects, while the orotic aciduria can result in a variety of symptoms, including growth retardation, anemia, and hyperammonemia. OTC deficiency is an X-linked genetic disorder and is the most common urea cycle disorder. 

8- c) Argininosuccinate synthase

Citrullinemia is a rare genetic disorder that affects the urea cycle, resulting in the accumulation of the amino acid citrulline and ammonia in the blood. Citrullinemia is caused by a deficiency in the enzyme argininosuccinate synthase (ASS), which catalyzes the formation of argininosuccinate from citrulline and aspartate.

9- b) Phenylbutyrate

The compound that is commonly administered to patients with urea cycle defects to remove ammonia is sodium phenylacetate/sodium benzoate. This medication works by conjugating with glutamine in the liver to form phenylacetylglutamine and hippuric acid, which can be excreted in the urine, thereby removing excess ammonia.
Sodium phenylacetate/sodium benzoate is typically given as an intravenous infusion in the hospital setting to treat acute hyperammonemia in patients with urea cycle disorders. It is often used in conjunction with other treatments, such as hemodialysis and supportive care. 

10- d) All of the above

Hyperammonemia is a medical condition characterized by an abnormally high level of ammonia in the blood. Ammonia is a toxic waste product that is produced by the body when proteins are broken down. Normally, the liver processes ammonia and converts it into urea, which is then eliminated from the body through urine.
There are several conditions that can lead to hyperammonemia, including:
Liver disease: Liver disease can impair the liver's ability to process ammonia, leading to a buildup of ammonia in the blood.
Urea cycle disorders: Urea cycle disorders are rare genetic disorders that affect the body's ability to convert ammonia into urea. This can result in hyperammonemia.
Gastrointestinal bleeding: Gastrointestinal bleeding can lead to the release of blood into the digestive tract, which can increase the amount of protein that is broken down in the body and produce more ammonia.
Certain medications: Certain medications, such as valproic acid and topiramate, can interfere with the liver's ability to process ammonia, leading to hyperammonemia.
Reye's syndrome: Reye's syndrome is a rare but serious condition that can occur in children who are recovering from a viral infection. It can cause hyperammonemia, as well as liver and brain damage.
Congenital portosystemic shunts: In this condition, blood is shunted around the liver, bypassing the organ's normal processing of ammonia. This can lead to hyperammonemia.

11- a) Alanine

Creatine is synthesized in a two-step process, which occurs mainly in the liver, kidney, and pancreas.
-Step 1: The first step involves the synthesis of guanidinoacetate from arginine and glycine. This reaction is catalyzed by the enzyme arginine:glycine amidinotransferase (AGAT), which transfers the amidino group from arginine to glycine to form guanidinoacetate.
- Step 2: The second step involves the methylation of guanidinoacetate to form creatine. This reaction is catalyzed by the enzyme guanidinoacetate methyltransferase (GAMT), which transfers a methyl group from S-adenosylmethionine (SAM) to guanidinoacetate, forming creatine. 

Alanine is not utilized for synthesis of creatine. 

12- b) CK-MB

Creatine kinase (CK) is an enzyme that catalyzes the conversion of creatine and ATP to phosphocreatine and ADP, which is an important reaction in energy metabolism. CK exists in different isoforms, which are tissue-specific and have different subunit compositions:
- CK-MM (muscle type): This isoform is primarily found in skeletal and cardiac muscle tissue and is composed of two identical muscle-specific subunits.
- CK-MB (heart type): This isoform is mainly found in cardiac muscle tissue and is composed of two subunits, one muscle-specific and one brain-specific.
- CK-BB (brain type): This isoform is mainly found in brain and smooth muscle tissue and is composed of two identical brain-specific subunits.
These isoforms are important in clinical diagnosis of certain medical conditions. For example, an elevated level of CK-MB in the blood is indicative of myocardial infarction or heart muscle damage, while an elevated level of CK-BB is indicative of brain damage. The ratio of CK-MB to CK-MM is also used in diagnosing myocardial infarction. 

13- a) CK-MM

Creatine kinase (CK) is an enzyme that catalyzes the conversion of creatine and ATP to phosphocreatine and ADP, which is an important reaction in energy metabolism. CK exists in different isoforms, which are tissue-specific and have different subunit compositions:
- CK-MM (muscle type): This isoform is primarily found in skeletal and cardiac muscle tissue and is composed of two identical muscle-specific subunits.
- CK-MB (heart type): This isoform is mainly found in cardiac muscle tissue and is composed of two subunits, one muscle-specific and one brain-specific.
- CK-BB (brain type): This isoform is mainly found in brain and smooth muscle tissue and is composed of two identical brain-specific subunits.
These isoforms are important in clinical diagnosis of certain medical conditions. For example, an elevated level of CK-MB in the blood is indicative of myocardial infarction or heart muscle damage, while an elevated level of CK-BB is indicative of brain damage. The ratio of CK-MB to CK-MM is also used in diagnosing myocardial infarction. 

14- d) Creatinine is not secreted by kidney tubules

Creatine is metabolized and excreted from the body primarily through the kidneys. After being synthesized in the liver and transported to other tissues, such as muscle, creatine is phosphorylated by creatine kinase to form phosphocreatine, which is stored in muscle tissue and can be rapidly converted back to creatine to produce ATP during high-intensity exercise.
During normal metabolic processes, creatine is degraded into creatinine, a waste product that is excreted in the urine. Creatinine levels in the blood and urine are often used as markers of kidney function, since creatinine is filtered out of the blood by the kidneys and excreted in the urine.

15- b) estimation of glomerular filtration rate

Creatinine clearance is a laboratory test that is used to measure how well the kidneys are functioning by estimating the rate at which creatinine is cleared from the blood. Creatinine is a waste product that is produced during the normal metabolism of muscle tissue, and it is filtered out of the blood by the kidneys and excreted in the urine.
To perform a creatinine clearance test, a blood sample and a 24-hour urine sample are collected from the patient. The amount of creatinine in the blood and urine is then measured, and the creatinine clearance is calculated using the following formula:
Creatinine clearance = (urine creatinine concentration x urine volume) / (plasma creatinine concentration x time)
The creatinine clearance value is expressed in units of milliliters per minute (ml/min), and it provides an estimate of the glomerular filtration rate (GFR), which is a measure of how well the kidneys are able to filter waste products out of the blood. 

16- d) All of the above

Several conditions can lead to increased production of uric acid, including:
Gout: Gout is a type of arthritis that occurs when uric acid crystals build up in the joints, causing pain, inflammation, and swelling. It results from the overproduction or underexcretion of uric acid, leading to elevated levels in the blood.
Lesch-Nyhan syndrome: Lesch-Nyhan syndrome is a rare genetic disorder that results in the overproduction of uric acid due to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This leads to the formation of uric acid crystals in the joints and kidneys, causing gout and kidney stones.
Tumor lysis syndrome: Tumor lysis syndrome is a medical emergency that can occur in patients undergoing chemotherapy for cancer. It results from the rapid breakdown of cancer cells, which releases large amounts of uric acid into the bloodstream, leading to hyperuricemia and acute kidney injury.
Metabolic syndrome: Metabolic syndrome is a cluster of conditions, including obesity, high blood pressure, and insulin resistance, that increase the risk of developing gout and other metabolic disorders. It is associated with an increased production of uric acid due to insulin resistance and altered glucose metabolism.
Excessive alcohol consumption: Excessive alcohol consumption can lead to increased uric acid production by interfering with the liver's ability to metabolize uric acid. It also increases the risk of dehydration, which can lead to the formation of uric acid crystals in the joints and kidneys.

17-c) Glutamine
Glutamine is a key amino acid involved in the transport of ammonia from peripheral tissues to the liver. In peripheral tissues, excess ammonia is converted to glutamine through a reaction catalyzed by the enzyme glutamine synthetase. The addition of the ammonia molecule to glutamate to form glutamine requires ATP.
Glutamine is then transported to the liver via the bloodstream, where it undergoes a reaction catalyzed by the enzyme glutaminase to release the ammonia molecule. The ammonia is then utilized in the urea cycle to form urea and be excreted in the urine.

18-a) Amino acids

Several metabolites are excreted via urine to maintain nitrogen balance in the body. These include:
- Urea: Urea is the primary metabolite excreted via urine to eliminate excess nitrogen from the body. It is produced in the liver through the urea cycle and excreted by the kidneys.
- Creatinine: Creatinine is a byproduct of muscle metabolism and is excreted by the kidneys. The level of creatinine in the blood is used as a measure of kidney function.
- Uric acid: Uric acid is a waste product of purine metabolism and is excreted by the kidneys. High levels of uric acid in the blood can lead to the formation of urate crystals, which can cause gout.
- Ammonia: Ammonia is a toxic byproduct of amino acid metabolism that is converted to urea in the liver and excreted by the kidneys.

19-d) Gluconeogenesis

Citrullinemia is a metabolic disorder caused by a deficiency in the enzyme argininosuccinate synthase, which is involved in the urea cycle. This results in the accumulation of ammonia and other toxic metabolites in the blood,
In citrullinemia, the accumulation of toxic metabolites such as ammonia and glutamine can lead to a decrease in the availability of these precursors for gluconeogenesis. This can lead to hypoglycemia and other metabolic disturbances.

20-d) Arginine succinate
The synthesis of urea from ammonia and bicarbonate in the urea cycle requires several intermediate reactions, and ATP is required for the generation of some of these intermediates.
Specifically, the synthesis of carbamoyl phosphate from ammonia and bicarbonate in the first step of the urea cycle requires the input of two ATP molecules. This reaction is catalyzed by the enzyme carbamoyl phosphate synthase I (CPSI), which is located in the mitochondria of liver cells.
Argininosuccinate is an intermediate in the urea cycle that requires ATP for its generation. Argininosuccinate is formed in the fourth step of the urea cycle, where citrulline reacts with aspartate in the presence of the enzyme argininosuccinate synthase.

21-b) Uric acid

The end product of purine metabolism in humans is uric acid. Purines are nitrogen-containing compounds that are important building blocks of DNA and RNA. When purines are broken down, they are converted into uric acid through a series of metabolic reactions.
Uric acid is a waste product that is normally excreted from the body through the urine.