Bio Chem enz contd 8-1 Flashcards
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 ?
Cytosol
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.
