Bio Chem enz 8-1 contd

Question 1

The patient’s protuberant abdomen, palmar erythema (redness of the palms), pronounced gynecomastia (swollen breast tissue), jaundice, and altered mental status are most concerning for?

Answer 1

hepatic encephalopathy from liver disease (cirrhosis).

Hepatic encephalopathy is thought to result from high ammonia levels exerting a toxic effect on neurons in the central nervous system. Significant liver damage and portosystemic shunting, leads to decreased ammonia metabolism by the urea cycle, which occurs exclusively in the liver, and consequent hyperammonemia. The injured liver fails to process ammonia into nontoxic metabolites as it would normally do.

Question 2

In a patient with signs of cirrhosis presenting with altered mental status, hepatic encephalopathy secondary to hyperammonemia is the most likely diagnosis. The urea cycle plays an integral role in converting amino acid byproducts (i.e. ammonia) into urea. Ammonia is shuttled to the liver via alanine, whose amino group is transferred to α-ketoglutarate to form glutamate, a precursor for the urea cycle. Therefore, excess ammonia will deplete?

Answer 2

α-ketoglutarate.

Question 3

Because the urea cycle is upregulated in the setting of increased ammonia, there would be an increase, not a decrease, in levels of carbamoyl phosphate, as it is an important byproduct of the urea cycle.
Because they are important carriers of ammonia in the bloodstream thereby preventing toxic damage, there would be increased, not decreased, production of glutamine and utilization of glutamate in the setting of increased ammonia.
Finally, there will be increased, not decreased, production of pyruvate due to?

Answer 3

increased levels of alanine aminotransferase from liver damage. Deamination of alanine generates pyruvate.

Question 4

This patient presents with early-onset joint pain and stiffening, skin hyperpigmentation, limited range of motion of the large joints, and a systolic murmur in the aortic area. Together, these signs and symptoms suggest the autosomal recessive disorder alkaptonuria. This disease is caused by a deficiency in the enzyme?

Answer 4

homogentisic acid oxidase, resulting in an accumulation of homogentisic acid. Excess homogentisic acid leads to inhibition of the enzyme lysyl hydroxylase, which is crucial for collagen cross-linking, contributing to the ochronotic arthritis.

Homogentisic acid is an intermediate product in the metabolism of phenylalanine and tyrosine and cannot be further metabolized without functional homogentisic acid oxidase

Question 5

Cystine should be limited in cystinuria, an autosomal recessive condition that causes defective dibasic amino acid transport and resulting nephrolithiasis due to insolubility of cystine.
Vitamin D would be elevated in a patient with vitamin D toxicity, which could be caused by excess intake of supplemental vitamin D pills.

Homocysteine is elevated in homocystinuria, an autosomal recessive condition that usually causes a deficiency in enzymes responsible for homocysteine metabolism. It does not cause the phenotype present in this patient.

Triglycerides should be limited as part of a balanced diet to ?

Answer 5

prevent dyslipidemia. Familial dyslipidemias would result in very high levels of triglycerides.

Leucine restriction is part of the management of maple syrup urine disease, an autosomal recessive disease that results in impaired branched amino acid metabolism. It does not cause the phenotype present in this patient.

Question 6

A 16-year-old boy is brought to the emergency department (ED) by his parents due to weakness. He had been feeling fine until he returned yesterday from a multiday camping trip in the wilderness, where he brought along some peaches that his grandmother had canned 3 years ago. After returning home, he started having difficulty swallowing and speaking. When he was unable to hold his head up, his parents decided it was time to come to the hospital. His vital signs in the ED are within normal limits. On cranial nerve exam, he has weakness in pushing his tongue against the side of his mouth bilaterally. He has weakness in head flexion and extension. Strength is 3/5 in the upper extremities and 4/5 in the lower extremities bilaterally. Sensation is normal throughout. The rest of the exam is unremarkable.

Which of the following proteins is required for transmission of this patient’s disease into the central nervous system?

Answer 6

The patient described in the vignette is suffering from botulism, likely caused by the ingestion of preformed botulinum toxin from poorly sealed cans on his camping trip. Botulism presents as descending paralysis with no changes in sensation.

Question 7

Microtubules are made of two subunits, α and β, that polymerize to form the hollow tubules that make up flagella, cilia, mitotic spindles, and neural axons. Anterograde transport along microtubules is performed by the motor protein kinesin, wherease retrograde transport is performed by?

Answer 7

dynein. Botulinum toxin works by blocking the release of neurotransmitters at the neuromuscular junction. The toxin is taken up by enteric nerve fibers and undergoes retrograde transport along axonal microtubules into the central nervous system (CNS). Here the toxin moves into motor neurons where it travels to the neuromuscular junction. At the neuromuscular junction, the toxin prevents the release of ACh, therby causing paralysis.

Question 8

Intermediate filaments of muscle cells are made up primarily of desmin.
Clathrin is a vesicular trafficking protein involved in transporting vesicles from the Golgi to the lysosomes, as well as from the plasma membrane to endosomes in receptor-mediated endocytosis.
Titin, also known as connectin, is a protein important in the contraction of striated muscle tissues. In the sarcomere, titin connects the M line to the Z line.
Kinesin is a motor protein that facilitates ?

Answer 8

anterograde axonal transport along microtubules. It plays a part in transporting botulinum toxin out of the CNS to reach the neuromuscular junction.

Question 9

This patient presents with progressively worsening shortness of breath, diminished bilateral breath sounds, and decreasing pulmonary function (ie, decreased ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC]). He also has abdominal tenderness and elevated transaminase levels. Together with his nonsmoking status and relatively young age, these findings indicate a diagnosis of α1-antitrypsin deficiency. α1-Antitrypsin deficiency is a genetic disease characterized by a deficiency in ?

Answer 9

the serine protease inhibitor α1-antitrypsin.

Question 10

Deficiency of α1-antitrypsin, a serine protease inhibitor, leads to ?

Answer 10

panacinar emphysema, cirrhosis of the liver, and panniculitis of the skin in a young patient who typically has no history of smoking.

Question 11

A genetic mutation resulting in deficient levels of a protease would involve deficiency of elastase, which would not result in panacinar emphysema. Mucous gland hypertrophy and hyperplasia are characteristic of chronic bronchitis and would not explain this patient’s elevated transaminase levels. Cystic fibrosis is caused by a mutation of the CFTR gene and would present with recurrent infections, pancreatitis, and malabsorption from an early age. Bronchial hyperresponsiveness occurs in ?

Answer 11

asthma—a condition unlikely to cause progressive deterioration of pulmonary function and elevated transaminase levels.

Question 12

This patient is presenting with classic symptoms of Sjögren syndrome, including keratoconjunctiva sicca (dry eyes) and xerostomia (dry mouth). Sjögren’s syndrome is an autoimmune disease characterized by reduced salivary and lacrimal function, which commonly coexists with rheumatoid arthritis. A salivary gland biopsy from the lower lip can show lymphocytic infiltrates, and antibodies against the Ro/La antigens may also help in the diagnosis of Sjögren’s syndrome. In the setting of dry eye, a Schirmer test using a folded strip of paper with <5 mm of wetting after 5 min is a tool used to measure extent of dry eye. Treatment of Sjögren syndrome involves?

Answer 12

immunomodulation drugs like methotrexate and hydroxychloroquine, though to treat ocular dryness and xerostomia, pilocarpine may be used.

Question 13

M3 receptors stimulate the Gq pathway. Qq stimulation activates phospholipase C (PLC) which stimulates cleavage of phosphatidylinositol bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 increases ?

Answer 13

release of intracellular Ca2+ which is utilized by DAG to activate protein kinase C (PKC). Other receptors utilizing this pathway include H1, α1, V1, and M1.

Question 14

Adenylyl cyclase cleaves adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and inorganic phosphate (PPi). It is stimulated by Gs and blocked by Gi. M3 receptors do not utilize the Gs pathway, making this answer choice incorrect.

Protein kinase A is stimulated by?

Answer 14

cyclic adenosine monophosphate (cAMP), which is a product of Gs si

Question 15

Protein kinase C (PKC) is one of the second messengers involved in the Gq pathway, which is utilized by M3 receptors in the gastrointestinal tract. However, PKC would be activated, not deactivated, upon stimulation of ?

Answer 15

M3 receptors. Ligand binding (stimulation) to the M3 receptor activates phospholipase C (PLC). PLC cleaves phosphatidylinositol bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 is then released into the cytoplasm where it binds to endoplasmic or sarcoplasmic reticulum, facilitating release of Ca2+ intracellularly. DAG remains membrane bound, and together with the intracellular Ca2+ increase, activates protein kinase C (PKC). PKC subsequently goes on to phosphorylate many substrates.

Question 16

A pediatric patient demonstrates gait disturbance, intellectual impairment, ataxia, upper motor neuron signs (hyperreflexia), and peripheral neuropathy with suspected cerebroside accumulation in the brain. These findings are most likely indicative of a deficiency in ?

Answer 16

arylsulfatase A.

This enzyme is deficient in patients with metachromatic leukodystrophy, an autosomal recessive lysosomal storage disease caused by mutations in the arylsulfatase A gene. This results in an inability to desulfate cerebroside sulfate, a major glycolipid of myelin, leading to the accumulation of cerebroside sulfate in the central nervous system, peripheral nerves, kidneys, and other visceral organs. The accumulation of cerebroside sulfate destroys oligodendroglial and Schwann cells, causing central and peripheral demyelination.

Question 17

Fabry disease is associated with a deficiency in a-galactosidase A, leading to an increase in ceramide trihexoside. Individuals demonstrate peripheral neuropathy of the hands and feet, nausea, abdominal pain, reduced sweating, and the cutaneous lesions of angiokeratoma.
Krabbe disease is associated with a deficiency in galactocerebrosidase, leading to an accumulation of psychosine (galactosylsphingosine) and galactocerebroside. Patients with juvenile-onset disease typically show weakness, loss of skills, and vision loss.

Tay-Sachs disease is associated with a deficiency in ?

Answer 17

hexosaminidase A, leading to an accumulation of GM2 ganglioside. Typically, infants at 2–6 months of age develop progressive weakness and loss of motor skills with hypotonia, hyperreflexia, and characteristic cherry red macula.
Niemann-Pick disease type A/B is associated with a deficiency in sphingomyelinase, leading to an accumulation of sphingomyelin. Clinically, patients show signs of hepatosplenomegaly, interstitial lung disease, macular cherry red spot, developmental regression, and variable neurologic deficits.

Question 18

This premature infant presents with difficulty breathing and evidence of use of accessory muscles of respiration. An x-ray demonstrates that the lungs have a diffuse ground glass appearance. These findings indicate a diagnosis of ?

Answer 18

neonatal respiratory distress syndrome (NRDS). NRDS is caused by low levels of surfactant, a naturally produced colloid that reduces surface tension in alveoli and makes it easier for infants to breathe.

Phosphatidylcholine, also known as lecithin, is the dominant component of pulmonary surfactant. Pulmonary surfactant consists of phospholipids (85%), proteins (10%), and neutral lipids (5%). About 75% of the phospholipids in surfactant are composed of phosphatidylcholine.

Question 19

The lecithin-sphingomyelin (L/S) ratio in amniotic fluid is a marker of fetal lung maturity. The rate of sphingomyelin production is fairly stable during the pregnancy, but the lecithin concentration varies depending on the amount of surfactant, which is produced by type II pneumocytes in the 36th week of gestation. Lower lecithin (phosphatidylcholine) levels indicate ?

Answer 19

that the lungs are immature. An L/S ratio of >2 to 2.5 usually indicates fetal lung maturity.

Surfactant, produced by type II pneumocytes, lines the alveoli. By reducing surface tension, surfactant prevents the alveoli from collapsing. Because premature infants can be deficient in surfactant, they are at increased risk for NRDS. If delivery can be delayed, the mother can be given glucocorticoids, which can help induce production of surfactant in the fetus.

Question 20

This patient’s lethargy and diaphoresis are consistent with hypoglycemia. In the setting of vomiting and recent addition of fruit juice (ie, fructose) to his diet, this patient most likely has hereditary fructose intolerance, a deficiency in ?

Answer 20

aldolase B. Aldolase B is important in the conversion of fructose-1-phosphate from fruit to products that can be used in glycolysis. Therefore a deficiency in aldolase B results in the underutilization of the glycolysis pathway and an accumulation of fructose-1-phosphate. Accumulation of fructose-1-phosphate has the unfortunate consequence of inhibiting gluconeogenesis, making patients susceptible to episodes of hypoglycemia and lactic acidosis. Other abnormalities include signs and symptoms of liver dysfunction, such as vomiting and failure to thrive.

Question 21

This patient is more likely to have acidemia than alkalemia because he is likely undergoing anaerobic metabolism to produce energy, and consequently, produces lactic acid as a byproduct. Because adenosine triphosphate (ATP) is being depleted, the patient would be more likely to have hypophosphatemia than hyperphosphatemia. Additionally, because ATP binds magnesium, a low level of ATP would result in an increase in free magnesium, or hypermagnesemia (not hypomagnesemia). Finally, this young patient does not have the signs or symptoms associated with ?

Answer 21

hypocalcemia, such as paresthesias, muscle cramps, perioral numbness, carpopedal spasm, seizures, and tetany.

Question 22

This experiment concerns the renal production of glucose, which may account for up to 40% of gluconeogenesis in the postabsorptive state. The liver has been removed in both groups of rats, eliminating any effects of hepatic glucose production. Therefore the fact that 14C-labeled glucose falls faster than total glucose in the rats with kidneys indicates that the kidneys must be producing endogenous (unlabeled) glucose that is contributing to the total serum glucose concentration. This glucose is unlabeled because its precursors (ie, glycerol and lactate) are not labeled.
The kidneys produce this glucose largely through gluconeogenesis (85%), and to a lesser extent, glycogenolysis (15%). Several enzymes are unique to ?

Answer 22

the gluconeogenesis pathway, but fructose-1,6-bisphosphatase is the rate-determining enzyme in renal gluconeogenesis and is thus the correct answer. This question requires you to recognize that gluconeogenesis—and not glycogenolysis—is the major contributor to renal glucose release and then to recall which enzyme is rate limiting in gluconeogenesis (fructose-1,6-bisphosphatase).

Question 23

Citrate synthase is an enzyme in the tricarboxylic acid cycle that would be inhibited by a hypoglycemic state. Although glycogen phosphorylase is found in the kidneys and can contribute to renal glucose release, it is involved in glycogenolysis, not gluconeogenesis, so its contribution would be minor. Phosphofructokinase and pyruvate kinase are both enzymes that are involved in ?

Answer 23

glycolysis, not gluconeogenesis.

Question 24

A nondiabetic man consumes a carbohydrate-rich meal. His fasting blood glucose is 80 mg/dL, and his postprandial blood glucose rises to 160 mg/dL.

What enzymatic characteristic enables this patient to maintain normal postprandial glucose levels despite ingesting a high carbohydrate load?

Answer 24

The high Vmax of glucokinase
After glucose is ingested in the form of a carbohydrate meal, it can only be utilized by cells once it is phosphorylated to glucose-6-phosphate. The phosphorylation of glucose traps glucose within cells, effectively removing it from the circulation and thereby lowering blood glucose levels. The body uses two similar enzymes to phosphorylate glucose: hexokinase and glucokinase. Hexokinase is an enzyme that functions in most tissues; glucokinase functions exclusively in hepatocytes and pancreatic islet cells.
Compared with glucokinase, hexokinase has a greater affinity for glucose (a lower Km) but a lesser maximum enzymatic rate (a lower Vmax). Therefore, hexokinase can effectively bind small amounts of glucose and enhance phosphorylation, but the reaction rate is slow and the enzyme reaches its maximum velocity at a relatively low concentration of substrate. In contrast, glucokinase has a lower affinity for glucose (a high Km) but a greater maximum enzymatic rate (a greater Vmax).

Question 25

Glucokinase has a low affinity for glucose but a high capacity for activity; it is most active when glucose levels are high, helping the body handle large increases in ?

Answer 25

blood glucose, for example after a carbohydrate-rich meal.

Question 26

Hexokinase has a relatively low Michaelis-Menten constant (Km) compared with glucokinase.

Compared with glucokinase, hexokinase has a low Vmax. At higher glucose levels, for example, after a carbohydrate-rich meal, hexokinase is overwhelmed (low maximum reaction rate), but sufficient substrate is available for glucokinase to process the excess glucose load and restore glucose homeostasis.

The half-life of glucokinase (ie, its enzymatic stability) is not typically discussed in its relation to hexokinase or to glucose homeostasis.

The half-life of hexokinase (ie, its enzymatic stability) is not typically ?

Answer 26

discussed in its relation to glucokinase or to glucose homeostasis.

Glucokinase has a relatively high Michaelis-Menten constant (Km) compared with hexokinase.

Question 27

This patient’s symptoms suggest a neurologic disorder. His involuntary movements (chorea), depression, and irritability, combined with a family history of similar symptoms and cognitive decline, makes Huntington disease (HD) the most likely diagnosis. The condition usually manifests in patients between 20 and 50 years old, with dementia developing at later stages of the disease. Atrophy of the caudate nucleus and putamen may occur and, later in the disease course, the lateral ventricles may enlarge.
HD is associated with an increased number of CAG tandem repeats on ?

Answer 27

chromosome 4 and is an autosomal dominant trinucleotide repeat disorder. HD demonstrates anticipation, meaning that with each successive affected generation, the disease manifests earlier and gets worse faster, as shown in this patient.

Question 28

a-Synuclein aggregates are the intracellular pathology associated with Parkinson disease, which is characterized by slow abnormal movements, in contrast with the more rapid, involuntary movements associated with HD.
Tau protein aggregations are seen in Pick disease, which affects the frontal and temporal lobes, and Alzheimer disease, which affects the cortex. Both diseases manifest with memory loss and abnormal behavior. Alzheimer disease is also associated with increased amyloid ß-peptides.
Amytrophic lateral sclerosis has been associated with?

Answer 28

mutations in the SOD1 gene and leads to combinations of upper and lower motor neuron defects, such as difficulty swallowing and tremors.

Question 29

Huntington disease results from expansion of CAG repeats on chromosome 4. It is inherited in an autosomal dominant fashion. Classic symptoms include?

Answer 29

chorea (brief, irregular movements that are not repetitive or rhythmic), dementia, and mood changes.