Question 1

The waste nitrogen from skeletal amino acid catabolism is diverted to the liver for incorporation into urea in which of the following compounds?&#10;A) alanine&#10;B) asparagine&#10;C) aspartate&#10;D) glutamate&#10;E) phenylalanine

Accepted Answer

Alanine transports nitrogen from muscle to the liver, where it is converted to urea. Alanine transaminase has an important function in the delivery of skeletal muscle carbon and nitrogen (in the form of alanine) to the liver. In skeletal muscle, pyruvate is transaminated to alanine, thus affording an additional route of nitrogen transport from muscle to liver. In the liver, alanine transaminase transfers the ammonia to a-ketoglutarate and regenerates pyruvate. The pyruvate can then be diverted into gluconeogenesis. This process is referred to as the glucose-alanine cycle.

Question 2

When the body becomes acidotic the liver and the kidneys play central roles in reactions designed to reduce the pH of the blood. Which of the following constitutes the primary critical hepatic reaction occurring during periods of acidosis?

A) ammonia incorporation into glutamate forming glutamine
B) ammonia incorporation into a-ketoglutarate forming glutamate
C) glutamine conversion to glutamate releasing ammonia
D) glutamine conversion toa-ketoglutarate releasing ammonia
E) increased production of urea to dispose of ammonia

ammonia incorporation into glutamate forming glutamine

Accepted Answer

Major reactions that involve the regulation of plasma pH as well as the level of circulating ammonia involve the hepatic and renal enzymes glutamate dehydrogenase (GDH), glutamine synthase (GS), and glutaminase. The liver compartmentalizes GS and glutaminase in order to control the flow of ammonia into glutamine or urea. Under acidotic conditions the liver diverts ammonia to glutamine via the GS reaction. The glutamine then enters the circulation. In fact, glutamine is the major amino acid of the circulation and its role is to ferry ammonia to and from various tissues. In the kidneys, glutamine is hydrolyzed by glutaminase (yielding glutamate) releasing the ammonia to the urine. There the ammonia ionizes to ammonium ion, NH₄⁺, which reduces the circulating concentration of hydrogen ion resulting in an increase in the pH. Additionally, the glutamate can be converted to a-ketoglutarate yielding another mole of ammonia, which is ionized by hydrogen ions further increasing the pH.

Question 3

Glutamate dehydrogenase is an extremely important enzyme involved in nitrogen homeostasis. This enzyme catalyzes a reversible reaction that either incorporates or liberates ammonium ion. When catalyzing the reaction in the direction of ammonium ion liberation, the enzyme is allosterically activated by which of the following?

A) adenosine diphosphate (ADP)
B) adenosine triphosphate (ATP)
C) citrate
D) glutamine
E) guanosine triphosphate (GTP)

adenosine diphosphate (ADP)

Accepted Answer

ADP is an allosteric activator of glutamate dehydrogenase when catalyzing the reaction in the direction of ammonium ion liberation, promoting energy production.  Glutamate dehydrogenase uses both nicotinamide nucleotide cofactors; NAD+ in the direction of nitrogen liberation and NADPH for nitrogen incorporation. The reaction catalyzing the liberation of ammonia and a-ketoglutarate from glutamate is a key anaplerotic process linking amino acid metabolism with TCA cycle activity. This reaction allows glutamate to play an important role in energy metabolism. Glutamate dehydrogenase provides an oxidizable carbon source used for the production of energy as well as a reduced electron carrier, NADH. In the forward reaction, as shown in Figure 29-3, glutamate dehydrogenase is important in converting free ammonia and a-ketoglutarate to glutamate, forming one of the 20 amino acids required for protein synthesis. As expected for a branch point enzyme with an important link to energy metabolism, glutamate dehydrogenase is regulated by the cell energy charge

Question 4

Which of the following represents the major compound of the circulation responsible for transport of nitrogen?&#10;A) alanine&#10;B) asparagine&#10;C) glutamate&#10;D) glutamine&#10;E) uric acid

Accepted Answer

Glutamine is the major carrier of nitrogen in the blood, transporting excess nitrogen from tissues to the liver for excretion.  Glutamine is the major amino acid found in the circulatory system. Its role there is to carry ammonia to and from various tissues but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolyzed by the enzyme glutaminase; this process regenerates glutamate and free ammonium ion, which is excreted in the urine.

Question 5

Under acidotic conditions the liver will divert which of the following compounds to the kidneys as a means to increase the pH?&#10;A) ammonia&#10;B) asparagine&#10;C) glutamate&#10;D) glutamine&#10;E) urea

Accepted Answer

Under acidotic conditions, the liver converts glutamate to glutamine, which is then transported to the kidneys. In the kidneys, glutamine is deaminated to produce ammonia, which helps to buffer excess hydrogen ions and increase the pH. Major reactions that involve the regulation of plasma pH as well as the level of circulating ammonia involve the hepatic and renal enzymes glutamate dehydrogenase (GDH), glutamine synthase (GS), and glutaminase. The liver compartmentalizes GS and glutaminase in order to control the flow of ammonia into glutamine or urea. Under acidotic conditions the liver diverts ammonia to glutamine via the GS reaction. The glutamine then enters the circulation. In fact, glutamine is the major amino acid of the circulation and its role is to ferry ammonia to and from various tissues. In the kidneys, glutamine is hydrolyzed by glutaminase (yielding glutamate) releasing the ammonia to the urine. There the ammonia ionizes to ammonium ion, NH₄⁺, which reduces the circulating concentration of hydrogen ion resulting in an increase in the pH. Additionally, the glutamate can be converted to a-ketoglutarate yielding another mole of ammonia, which is ionized by hydrogen ions further increasing the pH

Question 6

You are examining a 6-month-old infant who is experiencing feeding difficulty and generalized hypotonia of the limbs. Additional symptoms reported to you by the infant's parents are strange eye movements tending to cause the eyeballs to rotate up that occur several times a day. Laboratory results indicate significant aminoaciduria and aminoacidemia. Which of the following enzymes is most likely defective in the infant?

A) l-amino acid oxidase
B) asparaginase
C) carbamoyl phosphate synthetase I
D) glutamate dehydrogenase
E) glutaminase

Accepted Answer

In the peroxisomes of mammalian tissues, especially liver, there exists a minor enzymatic pathway for the removal of amino groups from amino acids. l-amino acid oxidase is FMN-linked and has broad specificity for the l-amino acids. A number of substances, including oxygen, can act as electron acceptors from the flavoproteins. If oxygen is the acceptor the product is hydrogen peroxide, which is then rapidly degraded by the catalases found in liver and other tissues. Missing or defective l-amino acid oxidase is commonly associated with oculogyric crisis (OGC; spasmodic movements of the eyeballs that lasts several minute to hours) and causes generalized hyperaminoacidemia and hyperaminoaciduria, generally leading to neurotoxicity and early death.

Question 7

A deficiency of argininosuccinate synthetase (ASD) can be suspected in a neonate with elevated serum ammonia. To discriminate the fact that the hyperammonemia is indeed due to ASD and not due to a deficiency in other urea cycle enzymes, one can assay for the serum concentration of citrulline and orotic acid. Which of the following would best describe the expected findings?

A) both citrulline and orotate levels will be low
B) citrulline levels will be absent but orotate will be elevated
C) citrulline levels will be low but orotate levels will be elevated
D) citrulline levels will be 300 times normal, orotate will be near normal

Accepted Answer

In argininosuccinate synthetase deficiency, citrulline accumulates because it cannot be converted to argininosuccinate, leading to elevated citrulline levels. Orotate levels remain near normal because the block is after carbamoyl phosphate, which is the precursor for orotate. A urea cycle disorder (UCD) is likely in a neonate that has elevated serum ammonia appearing, not before, but between 24 and 48 hours after a normal term delivery. There are 3 hallmark symptoms associated with UCD. These are hyperammonemia, encephalopathy, and respiratory alkalosis. Thus, elevated serum ammonia is not, in and of itself, indicative of a specific defect in the urea cycle. An analysis of the levels of various amino and organic acids in the plasma and urine is the primary key to determining which defect led to the elevation in serum ammonia. Differential diagnosis of neonatal hyperammonemia as a consequence of a UCD can be accomplished by measurement of plasma citrulline and urinary orotic acid levels. Shown in Figure 29-9 is the standard differential diagnosis chart for determining which of the 4 possible neonatal UCDs are the causes of the hyperammonemia. First, the hyperammonemia appears in the absence of any significant acidosis or ketosis. If analysis of serum citrulline demonstrates that it is >1000 _mM, it is confirmed that the clinical symptoms are due to a deficiency in argininosuccinate synthetase. In this circumstance, it is not necessary to assay for levels of urinary orotic acid, but they would be expected to be normal.

Question 8

A newborn that developed seizures 2 days after birth was diagnosed with elevated serum NH4+, glutamate, and alanine. A neonatal urea cycle defect was suspected so a urinalysis was performed to assay for orotic acid and serum assayed for citrulline. The levels of both were found not to be elevated. A defect in which enzyme of the urea cycle would most likely account for the symptoms observed in this infant?

A) arginase
B) argininosuccinate lyase
C) argininosuccinate synthetase
D) carbamoyl phosphate synthetase I (CPS-I)
E) ornithine transcarbamoylase (OTC)

Accepted Answer

The absence of elevated orotic acid and citrulline levels suggests a defect in carbamoyl phosphate synthetase I (CPS-I), as this enzyme deficiency would lead to hyperammonemia without the accumulation of orotic acid or citrulline.  Differential diagnosis of neonatal hyperammonemia, as a consequence of a UCD can be accomplished by measurement of plasma citrulline and urinary orotic acid levels. Refer to Figure 29-9 which shows the standard differential diagnosis chart for determining which of the 4 possible neonatal UCDs are the causes of the hyperammonemia. First, the hyperammonemia appears in the absence of any significant acidosis or ketosis. If analysis of serum cuitrulline demonstrates undetectable levels, then deficiencies in argininosuccinate lyase and argininosuccinate synthetase can be eliminated as causes of the symptoms. Assay for levels of urinary orotic acid will allow a discrimination between carbamoyl phosphate synthetase I and ornithine transcarbamoylase deficiencies. Since the levels of orotic acid were found to be insignificant, the symptoms must be due to deficiency in carbamoyl phosphate synthetase I.

Question 9

A 2-day-old infant is brought to the ER suffering a seizure. Analysis of serum NH4+ reveals it to be quite high. Suspecting a urea cycle impairment the ER physician initiates hemodialysis which reduces the NH₄⁺ levels. Subsequent to the hemodialysis the infant is treated with supplemental arginine which maintains the reduction in serum NH₄⁺. The ability of arginine to render this effect stems from it's role in activating the synthesis of an activator of one of the enzymes of the urea cycle. Which of the following represents this potent activator whose synthesis is induced by arginine?

A) argininosuccinate
B) bicarbonate ion
C) fumarate
D) N-acetylcysteine
E) N-acetylglutamate

Accepted Answer

Arginine stimulates the synthesis of N-acetylglutamate, which is an essential activator of carbamoyl phosphate synthetase I, the first enzyme in the urea cycle.

Question 10

A child was born at home and developed seizures 2 days after birth. Upon examination in the ER it was found that the infant had elevated serum NH₄⁺, glutamate, and alanine. The ER physician suspected that the child was suffering from a defect in the urea cycle and ordered a urinalysis to assess the level of orotic acid and the serum was assayed for the level of citrulline. Orotic acid levels were above normal and citrulline was barely detectable. A defect in which enzyme of the urea cycle would most likely account for the symptoms observed in this infant?

A) arginase
B) argininosuccinate lyase
C) argininosuccinate synthetase
D) carbamoyl phosphate synthetase I (CPS-I)
E) ornithine transcarbamoylase (OTC)

Accepted Answer

The elevated orotic acid and low citrulline levels suggest a defect in ornithine transcarbamoylase (OTC), which leads to accumulation of carbamoyl phosphate that is converted to orotic acid.

Question 11

An individual harboring a mutation in OTC would be expected to exhibit which of the following measurable abnormalities?&#10;A) citrullinemia&#10;B) elevated urinary excretion of argininosuccinic acid&#10;C) elevation in blood orotic acid&#10;D) excess production of foam cells&#10;E) uric acid deposition in the joints

Accepted Answer

The answer of An individual harboring a mutation in OTC...

Question 12

A 2-day-old infant boy delivered by normal labor (with no known prenatal risk factors) has become lethargic and requires stimulation for feeding. When vomiting and hyperventilation ensued, routine laboratory results showed blood urea nitrogen (BUN) less than 1 mg/dL. The infant quickly lapses into a coma and was placed on a ventilator. Bulging of the fontanel suggested an intracranial hemorrhage, but a CT scan revealed only cerebral edema. Within several hours, the infant dies. Death is ascribed to sepsis; however, a postmortem analysis of the plasma samples taken at admission showed dramatically elevated serum ammonia and citrulline levels 100 times normal. Which of the following represents the enzyme deficiency associated with these severe neonatal symptoms?

A) argininosuccinate synthetase
B) carbamoylphosphate synthetase I
C) 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase
D) medium-chain acyl-CoA dehydrogenase
E) pyruvate carboxylase

Accepted Answer

The answer of A 2-day-old infant boy delivered by normal...

Question 13

Neonatal urea cycle defects are usually misdiagnosed because of a failure to assess which of the following?&#10;A) level of ammonia in the blood&#10;B) level of argininosuccinate in the blood&#10;C) level of citrulline in the blood&#10;D) level of orotic acid in the urine&#10;E) odor of acetone on the breath

Accepted Answer

The answer of Neonatal urea cycle defects are usually misdiagnosed...

Question 14

Which of the following would most likely be associated with a negative nitrogen balance?&#10;A) consuming a high-protein diet&#10;B) neonatal development&#10;C) post-starvation feeding&#10;D) pregnancy&#10;E) surgical recovery

Accepted Answer

The answer of Which of the following would most likely...

Question 15

An unconscious 37-year-old man is brought to the ER. His wife reports that they were at home having dinner celebrating his birthday. She indicates that normally he does not drink but they were having champagne for the celebration. She indicates that shortly after they finished the bottle he became disorientated and irritable and then he began experiencing delusions. When he began to have a seizure she called 911. By the time the ambulance arrived he was unconscious. Blood tests taken when he was admitted show significantly elevated serum ammonia. A deficiency in which of the following enzymes is most likely the cause of this patients symptoms?

A) alanine transaminase
B) asparaginase
C) citrin
D) glutamate dehydrogenase
E) glutaminase

Accepted Answer

The answer of An unconscious 37-year-old man is brought to...

Question 16

A child was born at home and developed seizures 2 days after birth. Upon examination in the ER it was found that the infant had elevated serum NH₄⁺, glutamate, and alanine. The ER physician suspected that the child was suffering from a defect in the urea cycle. Which of the following is the most appropriate course of action to take with this patient?

A) administer arginine via IV
B) administer glucose via IV
C) change the infants formula to one with no protein
D) give the infant fluids and continue to monitor symptoms
E) immediate hemodialysis

Accepted Answer

The answer of A child was born at home and...

Question 17

Which of the following vitamins is critically important in the overall process of nitrogen transfer from a-amino acids to a-keto acids? A) riboflavin B) thiamine C) vitamin B₆ D) vitamin B₁₂ E) vitamin C

Accepted Answer

The answer of Which of the following vitamins is critically...

Question 18

Under which of the following conditions would you most likely expect the glutamate dehydrogenase reaction to proceed in the direction of glutamate synthesis?&#10;A) high ATP:ADP ratio&#10;B) high NADH levels&#10;C) high NADPH levels&#10;D) low NADH levels&#10;E) low NADPH levels

Accepted Answer

The answer of Under which of the following conditions would...

Question 19

The most abundant end product of nitrogen metabolism in humans is which of the following?&#10;A) allantoin&#10;B) ammonium ion&#10;C) glutamine&#10;D) urea&#10;E) uric acid

Accepted Answer

The answer of The most abundant end product of nitrogen...

Question 20

Which of the following ketoacids provides the carbon skeleton for an amino acid capable of carrying 2 atoms of nitrogen per molecule from other tissues to the liver and kidney via the blood?&#10;A) acetoacetate&#10;B) a-ketoglutarate&#10;C) a-ketoisocaproic acid&#10;D) oxaloacetate&#10;E) pyruvate

Accepted Answer

The answer of Which of the following ketoacids provides the...

Question 21

A 3-day-old newborn female with a deficiency of mitochondrial carbamoyl phosphate synthetase I develops seizures and lapses into a coma. Which of the following changes in blood concentration is the most likely cause?

A) decreased glucose
B) increased ammonia
C) increased ketone bodies
D) increased lactate
E) increased urea

Accepted Answer

The answer of A 3-day-old newborn female with a deficiency...

Question 22

A 2-day-old male newborn develops lethargy, poor feeding, vomiting, and rapid respirations. He was delivered at term after an uncomplicated pregnancy. His brother died in infancy. He has been breast-fed since birth. Serum studies indicate an increased ammonia concentration and a nondetectable citrulline concentration. Urine orotic acid concentration is markedly increased. A deficiency in which of the following enzyme activities is the most likely cause of these findings?

A) branched-chain a-keto acid dehydrogenase
B) glucose 6-phosphatase
C) hypoxanthine-guanine phosphoribosyltransferase
D) medium-chain acyl-CoA dehydrogenase
E) ornithine transcarbmoylase

Accepted Answer

The answer of A 2-day-old male newborn develops lethargy, poor...

Question 23

Which of the following enzymes plays a key role in the formation of ammonium ions in the proximal renal tubule? A) carbonic anhydrase B) glucokinae C) glutaminase D) Na⁺/K⁺-ATPase E) PKA

Accepted Answer

The answer of Which of the following enzymes plays a...

Deck 29: Nitrogen: Nitrogen Homeostasis and Disposal Via Urea