BRS Biochem - Structure/Function

Question 1

this disorder affects the enzyme lysyl hydroxylase, results in a defect in collagen synthesis

Answer 1

Ehlers-Danlos syndrome
(hetergeneous group of disorders of collagen synthesis, marked by hyperextensible joints and skin, inheritance can be AR or AD, and at least one type is X-linked recessive)

Question 2

caused by mutations in FBN1 gene, leading to presence of mutant fibrillin protein in connective tissues

Answer 2

Marfan syndrome
(inherited as AD; many patients have cardiovascular defects, including mitral valve prolapse and cystic medial necrosis, leading to aortic incompetence and dissecting aortic aneurysms)

Question 3

a group of disorders involving the alpha1 and alpha2 chains of collagen usually inherited as AD trait

Answer 3

Osteogenesis imperfecta
(sometimes called brittle-bone disease; younger patients present with multiple childhood fractures, arousing suspicion of child abuse, and distinctive blue sclera)

Question 4

This AD condition is most often a result of mutations in the beta-myosin heavy chain gene, important in generating contractions within the cardiac myocytes

Answer 4

Familial hypertrophic cardiomyopathy
(disorder results in a disarray of the contaction apparatus within cardiac muscle cells, with the development of a thickened muscular wall; it can lead to sudden death due to arrhythmia in athletes)

Question 5

most cases are inherited as x-linked dominant mutations in the alpha5 chain of collagen type IV, which is expressed in the affected tissues

Answer 5

Alport syndrome
(characterized by nephritis, nerve deafness, and cataracts; presents with isolated hematuria)

Question 6

This disorder results from a frame-shift mutation leading to the complete absence of a cytoskeletal protein important in maintaining the shape of the contracting myocyte

Answer 6

Duchenne muscular dystrophy (DMD)
(this debilitating disorder leads to clumsiness, followed by weakness of the girdle muscles; confinement to a wheelchair occurs by the teens and death due to respiratory failure by the early 20s)

Question 7

this disorder results from a quantitative deficiency of the cytoskeletal protein dystrophin

Answer 7

Becker muscular dystrophy (BMD)

this disorder is much less severe than duchenne muscular dystrophy with a later onset and nearly normal life span

Question 8

Deficiency of the cytoskeletal protein spectrin, resulting in cells that are less deformable and more vulnerable to destruction in the spleen

Answer 8

Hereditary spherocytosis
(this autosomal dominant disorder is the most common inherited cause of hemolytic anemia in whites and results in spherical RBCs)

Question 9

This AR condition results from a defect in microtubule polymerization, with defects in neutrophil chemotaxis and phagolysosome formation

Answer 9

Chediak-Higashi syndrome
(defects in the formation of functional phagolysosomes from the union of lysosomes with phagosomes (containing opsonized pyogenic bacteria) results in recurrent infections by such organisms)

Question 10

this family of transcription factors contains the supersecondary structural helix-turn-helix motif and is important in pattern formation during embryonic development

Answer 10

Homeobox proteins
(known as hox genes, these transcription factors mediate DNA transcription by binding to DNA via helix-turn-helix motifs.  Disruption of such interactions during development by synthetic retinoids results in congenital malformations)

Question 11

this disorder results from an alteration in the normal alpha-helical arrangement of a neuronal protein, with conversion to a pathogenic beta-pleated sheet conformation after exposure to an infectious agent

Answer 11

Creutzfeld Jakob disease
(it is believed that the conformation of the endogenous protein is altered by a proteinaceous infections agent known as a prion. Accumulation of the pathogenic form results in death of the affected neurons and the development of involuntary movements and increasing dementia)

Question 12

this genetic disease is caused by the deletion of a phenylalanine residue at the 508th amino acid (deltaF508) of the transmembrane chloride ion channel

Answer 12

Cystic Fibrosis
(one of the most common genetic diseases among whites, CF is due to mutations in the cystic fibrosis transmembrane regulator (CFTR); is produces viscous mucous secretions and recurrent, potentially fatal pulmonary infections.)

Question 13

these intracellular proteins act as molecular chaperones, aiding in the proper folding of newly translated proteins

Answer 13

Heat-Shock Proteins
(mutations in these proteins are found in some cases of Charcot-Marie-Tooth disease (CMT), one of the most common heritable neuromuscular disorders.)

Question 14

mutations in this important anti-protease lead to misfolded protein within the cell, resulting in a quantitative deficiency in the circulating protein, which is important in the remodeling of lung tissue

Answer 14

Alpha antitrypsin (AAT) deficiency
(patients with AAT deficiency present with panacinar emphysema of the lungs (lower lobes) due to unchecked protease activity in the lung.  They also develop cirrhosis of the liver.)

Question 15

This substance, produced by the C cells of the thyroid, accumulates to form beta-pleated sheets known as amyloid in medullary carcinoma of the thyroid

Answer 15

Calcitonin
(this hormone, involved in calcium metabolism, is overproduced in medullary carcinoma of the thyroid. In at risk populations, serum levels of calcitonin are used to screen for this type of cancer.)

Question 16

This substance contributes to the insoluble beta-fibrils, or amyloid, that accumulates in the B-cell malignancy multiple myeloma

Answer 16

Immunoglobulin light chains
(Ig light chains produced in excess in multiple myeloma form the amyloid that accumulates in the kidney and heart, contributing to renal failure (myeloma kidney) and cardiomyopathy, both of which complicate the disease.)

Question 17

This disorder results from defects in the ability to add glucosylphosphatidylinositol (GPI) anchors posttranscriptionally to proteins destined to be covalently attached to the extracellular face of cell membranes

Answer 17

Paroxysmal nocturnal hemoglobinuria (PNH)
(the major consequence of this disorder is the inability to produce GPI-anchored complement regulatory proteins on the surface of red blood cells. As a consequence, patients develop bouts of hemolytic anemia with hemoglobinuria.)

Question 18

This macromolecular complex is responsible for degrading protein tagged for destruction by the addition of multiple ubiquitin molecules

Answer 18

Proteosome
(Bortezomib (Velcade) inhibits this complex and is used for the treatment of multiple myeloma and mantle cell lymphoma (rare form of non-Hodgkins lymphoma))

Question 19

this type of enzyme inhibitor binds to the active site of the enzyme, increasing the apparent Km without changing the Vmax

Answer 19

Competitive inhibitor
(physostigmine is a competitive inhibitor of acetylcholinesterase. It is used to potentiate the activity of the acetylcholine in the treatment of glaucoma and is also used to treat myasthenia gravis)

Question 20

this type of enzyme inhibitor does not bind to the active site of the enzyme and therefore does not change the Km of the reaction; however, it does change the Vmax

Answer 20

Noncompetitive inhibitor
(EDTA is a commonly used noncompetitive inhibitor during the collection of blood samples from patients. It chelates the calcium required for the activation of serum proteases and proteins on the coagulation pathway)

Question 21

These enzyme inhibitors bind irreversibly to the enzyme active site, therefore the inhibition increases with the length of exposure to the substance

Answer 21

Irreversible inhibitors (suicide inhibitor)
(the nerve gas tabun and sarin are irreversible inhibitors of acetylcholinesterase. They cause symptoms due to increased acetylcholine, namely blurred vision, sweating, diarrhea, chest tightness, rapid breathing, and mental status changes.)