Question 1

A 58-year-old man visits your office and complains about impotence. Upon questioning you learn that he is capable of erections, but that they do not last as long and that they are of lesser strength than previously. Which of the following neurotransmitters is primarily responsible for dilation of the penile artery during erections?

Accepted Answer

Nitric oxide is the primary neurotransmitter responsible for the dilation of penile arteries, facilitating increased blood flow and erection.  Nitric oxide has important neurotransmitter-like functions. Its short half-life, due to spontaneous decay, limits its range and action. Nitric oxide acts on smooth muscle cells in a generally inhibitory manner; it relaxes the GI muscles and sphincters and dilates blood vessels. Vascular relaxation allows more blood to flow into the penis resulting in increased tumescence. In blood vessels, nitric oxide is derived from endothelial cells and was originally identified as endothelium-derived relaxing factor (EDRF)

Question 2

Measurement of the rate of creatinine clearance is used as a key determinant of renal function. In which of the following tissues is creatinine generated?

Accepted Answer

Creatinine is generated in skeletal muscle as a breakdown product of creatine phosphate, which is used as a quick energy source in muscle cells.  In cardiac and skeletal muscle, highenergy phosphate is stored through the transfer of a phosphate from ATP to creatine generating creatine phosphate. Creatine is synthesized in liver from guanidoacetate. Guanidoacetate is derived from the amino acid arginine in the kidneys. In muscle cells, creatinine is a nonenzymatic metabolite of creatine phosphate. When measured in the serum, levels of creatinine are remarkably constant from day to day and are proportional to muscle mass. In renal dysfunction, the clearance of creatinine will be impaired and its levels will therefore rise in the serum. Although creatine is synthesized in the liver from guanidoacetate, which is produced in the kidney, it is not used by these 2 tissues. Once synthesized, creatine is transported to cardiac and skeletal muscle where it is phosphorylated and stored for future energy needs.

Question 3

The action of many vasodilators within the vasculature involves the influx of calcium ions. A defect in which of the following proteins would most likely result in reduced effectiveness of these types of drugs?

Accepted Answer

Calmodulin is a calcium-binding messenger protein that is essential for the activation of various enzymes and proteins, including those involved in vasodilation. A defect in calmodulin would impair calcium ion signaling, reducing the effectiveness of vasodilators that rely on calcium influx. Both endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) are constitutively expressed and regulated by CaS1U1P12+. The calcium regulation is imparted be the associated calmodulin subunits, thus explaining how vasodilators such as bradykinin effect smooth muscle relaxation as a consequence of increasing intracellular endothelial cell calcium levels. A defect in calmodulin would, therefore, lead to reduced calcium binding and consequent reduction in NOS activation.

Question 4

Creatine phosphate is a critically important molecule for the storage of readily available energy in skeletal muscle. The synthesis of creatine phosphate requires the input of which of the following amino acids?

Accepted Answer

Creatine phosphate synthesis involves the amino acid arginine, which, along with glycine and methionine, is used in the biosynthesis of creatine.  Creatine is synthesized in the liver by methylation of guanidoacetate using SAM as the methyl donor. Guanidoacetate itself is formed in the kidney from the amino acids arginine and glycine. Creatine is used as a storage form of high energy phosphate. The phosphate of ATP is transferred to creatine, generating creatine phosphate, through the action of creatine phosphokinase. The reaction is reversible such that when energy demand is high (eg, during muscle exertion) creatine phosphate donates its phosphate to ADP to yield ATP.

Question 5

A 50-year-old man comes to the physician because of difficulty sleeping. History taking indicates insomnia is most likely caused by work-related stress. Before recommending pharmacological intervention, the physician suggests drinking a glass of warm milk and eating a turkey sandwich before bedtime. Which of the following precursors of serotonin is found in these foods?

Accepted Answer

Tryptophan is an amino acid found in foods like milk and turkey, and it is a precursor to serotonin, which can help with sleep regulation. Serotonin is derived from the amino acid tryptophan. Low serotonin levels result in sleep disruption and sleep disorders, including insomnia. Stress is a common cause of low serotonin levels, resulting in a snowballing feedback cycle of disrupted sleep, depression, anxiety, and fatigue during the day.

Question 6

You are studying the effects of mineral depletion in laboratory mice. These mice are fed a chow lacking in the trace metal zinc for a period of 2 weeks. Analysis of neurotransmitter levels and function at this time indicates that GABA production is significantly reduced. Which of the following symptoms is most likely to be observed in these mice as a result of the effects of the zinc restricted diet?

Accepted Answer

Zinc deficiency can lead to reduced GABA production, which is an inhibitory neurotransmitter. This reduction can result in increased excitatory activity in the nervous system, leading to symptoms such as heightened excitability or seizures. The amino acid derivative, g-aminobutyrate (GABA) is a major inhibitor of presynaptic transmission in the CNS, and also in the retina. Neurons that secrete GABA are termed GABAergic. The activity of GAD requires pyridoxal phosphate (PLP) as a cofactor. PLP is generated from the B₆ vitamins through the action of pyridoxal kinase. Pyridoxal kinase itself requires zinc for activation. A deficiency in zinc or defects in pyridoxal kinase can lead to seizure disorders, particularly in seizure-prone preeclamptic patients (hypertensive condition in late pregnancy)

Question 7

A 37-year-old 32-week pregnant woman is brought to the emergency room after suffering several seizures. Additional symptoms found in this patient are swollen hands and feet, blood pressure 165/125, right quadrant belly pain, and significant proteinuria. The ER physician suspects the woman is suffering from preeclampsia. Additional blood work indicates a deficiency in zinc. Which of the following amino acids serves as substrate for an important enzyme whose activity is impaired by a deficiency in zinc and could therefore explain the signs and symptoms in this patient?

Accepted Answer

The glutamate derivative, g-aminobutyrate (GABA; also called 4-aminobutyrate) is a major inhibitor of presynaptic transmission in the CNS. Glutamic acid decarboxylase (GAD) catalyzes the decarboxylation of glutamic acid to form GABA. The activity of GAD requires pyridoxal phosphate (PLP) as a cofactor. PLP is generated through the action of pyridoxal kinase. Pyridoxal kinase itself requires zinc for activation. A deficiency in zinc or defects in pyridoxal kinase can lead to seizure disorders, particularly as seen in this preeclamptic patient.

Question 8

You are studying the replication characteristics of a cell line in culture. You find that the DNA in these cells fragments easily and does not replicate well. Analysis of components of the replication machinery and associated compounds shows that the levels of spermidine and spermine are significantly reduced compared to normal cells. A deficiency in which of the following enzymes could best explain the observations made with these cells?

Accepted Answer

Ornithine decarboxylase is involved in the synthesis of polyamines like spermidine and spermine, which are important for DNA stabilization and replication. A deficiency in this enzyme would lead to reduced levels of these polyamines, explaining the observed DNA fragmentation and poor replication.  Spermine and spermidine are polyamines whose functions include stabilization of DNA during the processes of replication. The initial step in polyamine synthesis is catalyzed by ornithine decarboxylase (ODC), which decarboxylates the amino acid ornithine producing putrescine

Question 9

You are examining the characteristics of erythrocytes from a patient who suffers from recurrent episodes of mild hemolytic anemia. Your analysis of these cells shows that they are highly sensitive to oxidative stress likely due to the fact that they contain significantly less glutathione than normal erythrocytes. A deficiency in which of the following enzymes is likely in these erythrocytes?

Accepted Answer

γ-Glutamylcysteine synthetase is the enzyme responsible for the first step in glutathione synthesis. A deficiency in this enzyme would lead to reduced glutathione levels, making erythrocytes more susceptible to oxidative stress.  Glutathione (GSH) is synthesized in the cytosol of all mammalian cells. The rate of GSH synthesis is dependent upon the availability of cysteine and the activity of the rate-limiting enzyme, g-glutamylcysteine synthetase (GCS).

Question 10

During a clinical study, an investigator examines the effects of monoamine oxidase inhibitors to treat certain types of major depressive and phobic anxiety disorders. The concentration of which of the following compounds is most likely to be increased as a result of this treatment?

Accepted Answer

Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamines, such as epinephrine, leading to increased levels of these neurotransmitters in the brain.  Epinephrine and norepinephrine are catabolized to inactive compounds through the sequential actions of catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO). Compounds that inhibit the action of MAO have been shown to have beneficial effects in the treatment of clinical depression and anxiety disorders.

Question 11

Genetic engineering has been used to create a strain of mice that are unable to synthesize dopamine. These mice can survive embryonic development only if they are rescued by the provision of an external source of dopamine. Which of the following genes would be the most likely target for inactivation to produce such dopamine deficient mice?

Accepted Answer

Tyrosine hydroxylase is the enzyme responsible for the conversion of tyrosine to L-DOPA, the precursor to dopamine. Inactivating this gene would prevent dopamine synthesis.  Tyrosine is the amino acid precursor for the synthesis of the catecholamines. The catecholamine neurotransmitters are dopamine, norepinephrine, and epinephrine. Tyrosine is transported into catecholamine-secreting neurons and adrenal medullary cells where catecholamine synthesis takes place. The first step in the process requires tyrosine hydroxylase. The hydroxylation reaction generates DOPA (3,4-dihydrophenylalanine); then DOPA decarboxylase converts DOPA to dopamine.

Question 12

Overproduction of which of the following hormones by a neoplasm is best diagnosed by an increase in urinary excretion of vanillylmandelic acid?

Accepted Answer

Vanillylmandelic acid (VMA) is a metabolite of catecholamines, such as epinephrine and norepinephrine. An increase in urinary VMA is indicative of excess production of these hormones, often due to a pheochromocytoma, a type of tumor that secretes catecholamines.  Epinephrine and norepinephrine are catabolized to inactive compounds through the sequential actions of catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO). The terminal catabolic product of the actions of these 2 enzymes is vanillylmandelic acid.

Quiz 31: Nitrogen: Amino Acidderived Biomolecules

Measurement of the rate of creatinine clearance is used as a key determinant of renal function. In which of the following tissues is creatinine generated?

The action of many vasodilators within the vasculature involves the influx of calcium ions. A defect in which of the following proteins would most likely result in reduced effectiveness of these types of drugs?

Creatine phosphate is a critically important molecule for the storage of readily available energy in skeletal muscle. The synthesis of creatine phosphate requires the input of which of the following amino acids?

During a clinical study, an investigator examines the effects of monoamine oxidase inhibitors to treat certain types of major depressive and phobic anxiety disorders. The concentration of which of the following compounds is most likely to be increased as a result of this treatment?

Overproduction of which of the following hormones by a neoplasm is best diagnosed by an increase in urinary excretion of vanillylmandelic acid?