Flashcards in Bio Chem enz contd 8-1 Deck (30):
This patient presents with anterior, central chest pain; shortness of breath; diaphoresis; and ST-segment elevations on an ECG. These signs and symptoms are suggestive of an?
acute myocardial infarction (MI). She most likely has homocystinuria, as evidenced by the clinical picture of a tall marfanoid habitus, downward and inward lens subluxation, and an ECG-confirmed acute MI at a young age. Intellectual disability is also a common finding in patients with homocystinuria.
Untreated homocystinuria increases a patient’s risk of experiencing thromboembolic events in the third decade of life. In fact, almost one-third of patients with untreated homocystinuria die of thrombotic complications by age 30.
Homocystinuria results in intellectual disability, marfanoid habitus, and lens subluxation. Untreated homocystinuria increases a patient’s risk for thromboembolic events in the third decade of life. The three types of homocystinuria are?
(1) cystathionine synthase deficiency (this enzyme uses vitamin B6 as a cofactor), (2) decreased affinity of cystathionine synthase for pyridoxal phosphate, and (3) methionine synthase deficiency.
Adenosine deaminase deficiency is seen in patients with a purine salvage deficiency and severe combined immunodeficiency (SCID). Patients with SCID have recurrent bacterial, viral, and fungal infections.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in ?
African-American individuals, and patients with this deficiency are at risk for hemolysis and free radical inflammatory responses. Although this patient is African American, she has no evidence of hemolysis.
A deficiency in methionine synthase can cause homocystinuria; however, this reaction uses vitamin B12, not B6. Methionine synthase converts homocysteine to methionine.
Phenylalanine hydroxylase deficiency is present in patients with ?
phenylketonuria. Symptoms include intellectual disability, musty body odor, growth retardation, fair skin, and eczema.
Pyruvate carboxylase is the first enzyme in gluconeogenesis. A deficiency in this enzyme would impair glucose synthesis.
Congenital deficiency of tyrosinase can result in albinism.
Antibiotics are widely used in clinical practice to fight infection. Antibiotics work in many different ways to inhibit bacterial growth, including blocking cell wall synthesis, disrupting cell membranes, and blocking protein synthesis.
Which of the following antibiotics inhibits bacterial 50S peptidyltransferase, an enzyme used in protein synthesis?
Chloramphenicol inhibits 50S peptidyltransferase. It is a bacteriostatic drug used in severe meningitis due to Haemophilus influenzae, Neisseria, and Streptococcus pneumoniae. Its use is limited to severe infections because of its serious toxicities, including aplastic anemia, bone marrow suppression, and gray baby syndrome.
Other antibiotics that inhibit the bacterial 50S subunit are erythromycin and clindamycin, which inhibit translocation of the growing bacterial peptide.
The aminoglycosides including gentamicin, neomycin, amikacin, tobramycin, and streptomycin act by binding to ?
the 30S subunit and disrupting its shape, thereby preventing initiation complex formation and causing misreading of mRNA. It is important to remember that aminoglycosides require oxygen for uptake and this explains why aminoglycosides are ineffective against anaerobes.
Clindamycin is used to treat anaerobic infections, particularly those above the diaphragm. The major drawback to clindamycin use is the occurrence of severe diarrhea and fever in cases of Clostridium difficile colitis. Though clindamycin does affect the 50S ribosome, the mechanism of action is to ?
inhibit translocation, preventing the movement of the peptide chain from the A site to the P site. It does not affect peptidyl transferase activity.
Tetracycline is a bacteriostatic antibiotic that acts on the 30S subunit to prevent protein synthesis. It is used in the treatment of many infections, most notably chlamydial infections and community-acquired pneumonia. Severe adverse reactions seen with tetracycline use include nausea and vomiting, inhibition of bone growth in children, and discoloration of teeth. The mechanism of action involves binding to?
the ribosomal 30S subunit, preventing aminoacyl-tRNA from binding to the mRNA-ribosome complex. Thus it inhibits the elongation step.
This young woman is experiencing severe cramps and a burning sensation in her legs after running. Combined with a finding of myoglobin in the urine and increased creatinine kinase, these symptoms point to a diagnosis of ?
McArdle disease, also known as glycogen storage disease type V.
Patients with McArdle disease have sufficient glycogen stored inside these muscle cells; however, during strenuous exercise, glycogen cannot be broken down, leading to painful cramps, burning, and soreness in the affected muscles. In extreme cases, myoglobinuria can result.
Defects in the Golgi apparatus can lead to I-cell disease, which manifests with corneal opacification, joint stiffness, and facial coarseness.
Mitochondrial defects can lead to?
muscle pain, but can also manifest with optic issues and is not temporally associated with exercise.
Proteasome defects lead to undegraded protein and can be seen in Parkinson disease, which manifests with movement abnormalities.
Defects of the rough endoplasmic reticulum are associated with?
inflammatory processes and lead to accumulation of proteins, but do not present as exercise-induced myoglobinuria.
The patient has persistent bone pain, leg enlargement, and weight loss with an X-ray suggestive of osteosarcoma (hyper- and hypolucent areas, destruction of the cortex, with a rise in the periosteum). In a young man with osteosarcoma, in the setting of multiple family members with a history of malignancies, a familial cancer syndrome should be suspected. In this case the pattern of malignancy (breast, brain, bone, adrenal gland) is suggestive of?
Li Fraumeni syndrome.
Li Fraumeni syndrome is caused by an autosomal dominant mutation of the tumor suppressor p53 gene located on chromosome 17.
von Hippel-Lindau syndrome is associated with an increased risk of angiomatosis, hemangioblastoma and pheochromocytoma.
Familial adenomatous polyposis is associated with ?
an increased risk of colorectal cancer.
Cowden syndrome is associated with an increased risk of breast cancer, thyroid disease, colorectal cancer, endometrial cancer and renal cell cancer.
BRCA-1 gene mutation is associated with an increased risk of ?
breast and ovarian cancer.
DNA damage secondary to chemical insult, oxidative stress, or ultraviolet radiation will activate p53, leading to arrest of cell-cycle progression, DNA repair, and apoptosis. Individuals with the mutation are at increased risk for neoplasms of the breast, brain, soft tissue (sarcomas), bone, and adrenal gland. The diagnostic criteria for Li-Fraumeni syndrome are:?
Age <45 years.
A first-degree relative diagnosed with any cancer at age <45 years.
Another first- or second-degree relative diagnosed with any cancer at age < 45 years or with a sarcoma at any age.
This patient has had multiple family members with characteristic Li Fraumeni malignancies at a young age, making it the most likely diagnosis. The patient should receive treatment for his osteosarcoma, and the family should receive counseling about genetic testing and any screening options that are warranted for those individuals in the family with the pathologic mutation.
This patient presents with neurologic deficits in hearing, vision, smell, and gait, accompanied by thick, dry, and scaly skin. These findings coupled with the accumulation of phytanic acid in multiple tissues on diagnostic testing suggest?
Peroxisomes contain enzymes involved in very-long-chain fatty acid metabolism. Refsum disease is a peroxisomal disorder that affects myelin sheath formation, leading to various neurologic deficits and thick, scaly skin.
Cytoskeletal abnormalities are implicated in several disease categories, including cardiovascular syndromes, some neurodegenerative syndromes, cancer invasion, and liver cirrhosis.
Endoplasmic reticulum, as a site of protein and steroid synthesis, may be implicated in a ?
host of diseases with neurologic findings.
Endosomes may be involved in the pathophysiology of Alzheimer disease and atherosclerosis.
Ribosomes, as the sites of protein synthesis, are involved in Diamond-Blackfan anemia and Shwachman-Diamond syndrome.
Mitochondrial disorders, such as inborn errors of metabolism and MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), can also produce ?
neurologic deficits similar to those seen in this patient. However, long-chain fatty acid accumulation would not be commonly seen in patients with mitochondrial disorders.
A 63-year-old man is admitted to the hospital with symptoms of hypertensive emergency (blood pressure of 200/130 mm Hg with headache, nausea, and vomiting). Nitroprusside treatment is initiated to lower his blood pressure; however, his headache returns accompanied by confusion and abdominal pain. In the body, nitroprusside is converted into nitric oxide and cyanide ions. When inappropriate doses or prolonged infusions are administered, nitroprusside exposure can lead to?
cyanide toxicity. Cyanide toxicity is characterized by nonspecific signs and symptoms such as headaches, confusion, seizures, vomiting, arrhythmias, cherry-red–colored lips and mucous membranes, and later the development of cyanosis.
Cyanide has a high affinity for binding the ferric ion (Fe3+) in mitochondrial cytochrome C. Binding of cyanide to cytochrome C causes inhibition of mitochondrial cytochrome C oxidase, the last step in the electron transport chain
Lead inhibits d-aminolevulinic acid dehydratase. Lead poisoning can result in abdominal pain, constipation, headaches, irritability, anemia, and neurologic deficits.
acetylcholinesterase and can present with symptoms of excess salivation, watery eyes, diarrhea, altered mental status, hyperhidrosis, and miosis.
Carbon monoxide poisoning impairs the release of oxygen from hemoglobin. Although it can also cause red lips and headache, the temporal association of this patient’s symptoms with the nitroprusside infusion makes this a less likely diagnosis.
Digitalis inhibits Na+-K+ ATPase and can result in ?
headaches, nausea, vomiting, and cardiac arrhythmias (not seen in this patient).
Patients with cyanide poisoning should receive?
sodium thiosulfate or hydroxocobalamin. Sodium thiosulfate acts as a sulfur donor to detoxify cyanide to thiocyanate, which can be eliminated. Hydroxocobalamin binds cyanide and forms the nontoxic cyanocobalamin, which is renally excreted.
This patient was found unconscious with a low respiratory rate, likely caused by ethanol and opioid intoxication resulting in respiratory depression. A low respiratory rate leads to ventilatory failure and retention of carbon dioxide, causing?
respiratory acidosis. These effects are signaled by the patient’s low pH and elevated partial pressure of carbon dioxide on arterial blood gas analysis; his normal bicarbonate level and normal base excess rule out a metabolic component.
Acidemia, as seen in this patient, is a condition that shifts the oxygen-hemoglobin dissociation curve to the right (see dotted line on image). In other words, hemoglobin's affinity for oxygen is reduced. This reduction in affinity enables increased delivery of oxygen to peripheral tissues where the pH is low. Other conditions that cause a right shift in the oxygen-hemoglobin dissociation curve include?
increased temperature, increased 2,3-bisphosphoglycerate (2,3-BPG), and increased metabolic demands, for example, in exercise. During exercise, lactic acid builds up in tissues and causes a metabolic acidosis that shifts the curve in the same way as respiratory acidosis.
This patient’s signs, symptoms and findings do not indicate inhalation of carbon monoxide (CO) and CO poisoning. CO stabilizes the relaxed form of hemoglobin so that it has increased affinity for oxygen, preventing oxygen from being unloaded to tissues. Protracted vomiting typically leads to metabolic alkalosis and an increase in pH, which causes?
hemoglobin to have an increased affinity for oxygen.
Decreased hematocrit does not intrinsically change the affinity of hemoglobin for oxygen.
This patient presents with ataxia, ophthalmoplegia, and confusion, which are symptoms of Wernicke encephalopathy. This syndrome is caused by ?
a thiamine deficiency that is most commonly seen in malnourished alcoholic patients. Other clues that this is an alcoholic patient include the known history of esophageal varices, witnessed fall, disorientation, combativeness, and inability to track the physician’s finger. Thiamine, also known as vitamin B1, is used as a cofactor for multiple enzymes, including α-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase.
Δ-Aminolevulinate synthase is the rate-limiting enzyme involved in heme synthesis, and it requires pyridoxine (vitamin B6) as a cofactor. A deficiency in pyridoxine, most commonly caused by isoniazid therapy, can lead to sideroblastic anemia and a cracking/scaling of the corners of the mouth (cheilosis).
Dopamine hydroxylase is a key enzyme in?
the synthesis of catecholamines, which convert dopamine to norepinephrine. Vitamin C is required for the enzyme to function. A deficiency can lead to scurvy.
Homocysteine methyltransferase is an enzyme involved in folate metabolism, in which it acts to convert ?
homocysteine to methionine. Cyanocobalamin (vitamin B12) is the cofactor for this enzyme. A deficiency can result in megaloblastic anemia and peripheral neuropathy.
Pyruvate carboxylase is an enzyme in the gluconeogenesis pathway, which converts?
pyruvate to oxaloacetate, a reaction that is essentially irreversible. The enzyme is activated by acetyl-CoA, and the cofactors are ATP and biotin. Biotin deficiency is relatively rare and is usually caused by total parenteral nutrition without biotin supplementation, antibiotic use, or excessive ingestion of raw egg whites.