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81 Cards in this Set
- Front
- Back
Fabry's Disease
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Sx - peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
deficient a-galactosidase A accum: ceramide trihexoside X-linked recessive |
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Gaucher's Disease
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Sx - hepatosplenomegaly, asceptic necrosis of femur, bone crisis, Gaucher's cells (mac's crumpled like tissue paper)
deficient b-glucocerebrosidase accum: glucocerebroside autosomal recessive |
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Niemann-Pick
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Sx - neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells
deficient sphingomyelinase accum - sphingomyelin autsosomal recessive |
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Tay-Sachs Disease
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progressive neurodegeneration, developmental delay, cherry-red spot, lysosomes w/ onion skin
Hexosamindase A deficiency GM2 ganglioside accumulates autosomal recessive |
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Krabbe's Disease
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peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Galactocerebrosidase deficiency Galactocerebroside accumulates |
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Metachromatic leukodystrophy
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Central and peripheral demyelination with ataxia, dementia
Arylsulfatase A deficiency Cerebroside sulfate accum autosomal recessive |
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Hurler's syndrome
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developmental delay, gargoylism, airway obstruction, corneal clouding
a-L-iduronidase deficient heparan sulfate, dermatan sulfate accumulates autosomal recessive |
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Hunter's syndrome
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Mild hurler's + aggressive behavior, no corneal clouding
iduronate sulfate deficient heparan sulfate, dermatan sulfate accumulate x-linked recessive |
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Adult polycystic kidney disease
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Always bilateral, massive enlargement of kidneys due to multiple large cysts. Presents w/ pain, hematuria, HTN, progressive renal failure. 90% of cases due to mutation in APKD1 on chr 16. Associated w/ polycystic liver disease, berry aneurysms, mitral valve prolapse. Juvenile form in recessive.
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Familial hypercholesterolemia
hyperlipidemia type IIA |
Elevated LDL owing to defective or absent LDL receptor. Heterozygotes have cholesterol ~300, homozygotes (rare) have cholesterol 700+, severe atherosclerotic disease early in life, tendon xanthomas esp in Achilles tendon, MI before age 20.
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Marfan's syndrome
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Fibrillin (sheath of elastin) gene mutation causing connective tissue disorders.
Skeletal abnormalities - tall with long extremities, pectum excavatum, hyperextensive joints, long, tapering fingers and toes - arachnodactyly Cardiovascular - cystic medial necrosis of aorta, leading to aortic incompetence and dissectin aortic aneurysms. Floppy mitral valve. Ocular - subluxation of lenses |
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Neurofibromatosis type 1
von Recklinghausen's disease |
Findings - cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (scoliosis), optic pathway gliomas, pheochromocytomas, increased tumor susceptibility. on chr 17
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Neurofibromatosis type 2
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Bilateral acoustic neuromas, jeuvenile cataracts, NF2 gene on chr 22
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Tuberous sclerosis
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facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas. incomplete penetrance, variable presentation.
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von Hippel-Lindau disease
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hemangioblastomas of retina/cerebellum/medulla. about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors. Assoc w/ deletion of VHL gene (tumor suppressor) on chr 3, von Hippel Lindau - three words for chr 3
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Huntington's disease
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Depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of GABA and ACh in the brain. Sx manifest in affected individuals b/n ages of 20-50. Located on chr 4; triplet repeat disorder.
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Familial adenomatous polyposis
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colon covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected. Deletion on chromosome 5 APC gene.
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Hereditary spherocytosis
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Spheroid erythrocytes; hemolytic anemia. increased MCHC. Splenectomy is curative.
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Achondroplasia
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Autosomal-dominant cell-signaling defect of fibroblast growth factor FGF receptor 3. Results in dwarfism; short limbs but head and trunk are normal size. Assoc w/ advanced paternal age.
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Vitamin A
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Deficiency - night blindness, dry skin
Function - constituent of visual pigments in retina. Found in leafy vegetables. Excess - Arthralgias, fatigue, headaches, skin changes, sore throat, alopecia. |
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Vitamin B1
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Thiamine
Deficiency - Beriberi (Dry - polyneuritis, symmetrical muscle wasting; wet - high-output cardiac failure, dilated cardiomyopathy, edema) and Wernicke-Korsakoff syndrome (confusion, ataxia, opthalmoplegia, hemorrhage and necrosis of mamillary bodies) Functions in thiamine pyrophosphate, a cofactor fo oxidative decarboxylation of a-ketoacids and branched chain AA dehydrogenase, and a cofactor for transketolase in HMP shunt. |
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Vitamin B2
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Riboflavin
Deficiency - Angular stomatitis (inflammation of oral mucous linings), Cheilosis (inflam of lips), Corneal vascularization Function - cofactor in oxidation and reduction, FAD and FMN - make 2 ATP |
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Vitamin B3
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Niacin.
Deficiency - made from body tryptophan, synthesis requires B6. Pellagra can be caused by Hartnup's disease (dec tryptophan absorption), malignant carcinoid syndrome (inc tryptophan metabolism), INH (dec B6) Pellagra = 3D's : Diarrhea, Dermatitis, Dementia (beefy glossitis) Constituent of NAD, NADP in redox rxns |
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Vitamin B5
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Panthogenate = part of CoA
Deficiency - dermatitis, enteritis, alopecia, adrenal insufficiency Function - constituent of CoA and component of fatty acid synthase |
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Vitamin B6
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Pyridoxine.
Deficiency - Convulsion, hyperirritability, peripheral neuropathy. deficiency inducible by INH and COC's) Function - converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation rxns, glycogen phosphorylase, heme synthesis. Required for synthesis of niacin from tryptophan |
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Vitamin B12
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Cobalamin.
Deficiency - macrocytic, megaloblastic anemia, neurologic symptoms ( optic neuropathy, subacute combined degeneration, paresthesia), glossitis. Function - Cofactor for homocystein methyltransferase, transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase. Stored primarily in the liver, very large reserve pool (several years). synthesized by microorganisms. In animal products. Causes - malabsorption, lack of intrinsic factor, absence of terminal ileum. |
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Folic Acid
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Most common vitamin deficiency in US
Deficiency - macrocytic, megaloblastic anemia w/ no neurologic symptoms. Function - Coenzyme for 1-carbon transfer; involved in methylation rxns, synthesis of nitrogenous bases. found in green leaves. |
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Biotin
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Deficiency - dermatitis, enteritis. Rare, caused by antibiotic sues, excessive ingestion of raw eggs.
Cofactor for carboxylations pyruvate to oxaloacetate Acetyl-CoA to malonyl CoA Propionyl-CoA to methylmalonyl-CoA |
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Vitamin C
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Scurvy - swollen gums, bruising, anemia, poor wound healing, petechiate
Necessary for hydroxylation of proline and lysine in collagen synthesis. Facilitations iron absorption by keeping in Fe2+ state Necessary as a cofactor for dopamine beta-hydroxylase, converts dopamine to NE |
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Vitamin D
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ergocalciferol form in milk
cholecalciferol formed in skin Deficiency - rickets in children, osteomalacia in adults, hypocalcemic tetany. Function - inc intestinal absorption of calcium and phosphate. Excess - hypercalcemia, loss of appetite, stupor. seen in sarcoidosis, disease where epithelioid mac's convert vit D to active form |
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Vitamin E
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Deficiency - increased fragility of erythrocytes, neurodysfunction.
Function - antioxidant |
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Vitamin K
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Deficiency - Neontatl hemorrhage w/ elevated PT and PTT, but normal bleeding time.
Function - catalyzes carboxylation of glutamic acid residues on various proteins concerned with blood clotting - factors II, VII, IX, X and proteins C and S. synthesized by intestinal flora - absent at birth and after antibiotic use. |
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Zinc deficiency
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Delayed wound healing, hypogonadism, decreased adult hair in axilla, facial, pubic, may predispsoe to alcoholic cirrhosis.
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Amino acids needed for purine synthesis
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Glycine
Aspartate Glutamate In the De novo pathway, purines are made from IMP precursor |
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Transition vs. Transversion
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Transition - substituting purine for purine or pyrimidine for pyrimidine
Transversion - substituting purine for pyrimidine or vice versa |
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DNA polymerase III
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Elongates the chain by adding deoxynucleotides to the 3' end (leading strand).
Elongates lagging strand until it reaches primer of preceding fragment. 3' --> 5' exonuclease activity proofreads each added nucleotide. |
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DNA polymerase I
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Degrades RNA primer (5' --> 3' exonuclease) and fills in the gap with DNA
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Stop codons
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UGA
UAA UAG |
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Cell Cycle regulators
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CDK - constitutive and inactive
Cyclins - phase specific, activate CDKs Rb and p53 tumor suppressors normally inhibit G1 to S progression. |
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I cell disease
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Failure of addition of mannose-6-phosphate lysosome proteins.
Enzymes are secreted outside the cell instead of being targeted to the lysosome. Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes. Often fatal in childhood |
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Chediak-Higashi syndrome
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due to a microtubule polymerization defect resulting in decreased phagocytosis, can't fuse lysosomes.
Increased susceptibility to infection, esp S. aureus, due to defects in chemotaxis, degranulation and bacteriocidal activity |
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Kartagner's syndrome
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Immotile cilia due to a dynein arm defect.
Results in male and female infertility, bronchiectasis, recurrent sinusitis. Associated w/ situs inversus |
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Osteogenesis imperfecta
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Variety of gene defects; all result in abnormal collagen synthesis.
Most common form is autosomal-dominant with abnormal collagen type I. 1. multiple fractures occuring with minimal trauma, during birth 2. Blue sclerae - translucency of connective tissue over the choroid 3. Hearing loss - abnormal middle ear bones 4. Dental imperfections - lack dentin |
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Metabolic processes in the mitochondria
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Fatty acid oxidation (beta)
acetyl-CoA production Krebs cycle oxidative phosphorylation |
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Metabolic processes in the cytoplasm
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Glycolysis
fatty acid synthesis HMP shunt Protein synthesis RER Steroid synthesis SER |
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Hexokinase vs. Glucokinase
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Hexokinase -
high affinity (low Km), low capacity (low Vmax), uninduced by insulin Glucokinase - low affinity (high Km) and high capacity (high Vmax), induced by insulin, only in liver and pancrease |
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Coenzymes required by pyruvate dehydrogenase complex
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1. Pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin) 3. NAD (B3, niacin) 4. CoA (B5, pantothenate) 5. Lipoic acid Arsenic inhibits lipoic acid and results in vomiting, rice water stools, garlic breath. |
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Alkaptonuria
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Deficient homogentiasate oxidase
Accumulate homogentisate Black urine and cartilage, degenerative arthritis |
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Galactosemia
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Galactose 1-phosphate uridyltransferase deficiency
accumulate galactose 1-phosphate Mental retardation, cirrhosis, hypoglycemia.cataracts (galactitol) Avoid dairy products |
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Hereditary fructose intolerance
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deficient Aldolase B
accumulate fructose 1-phosphate Cirrhosis, hypoglycemia, renal disease Avoid fructose, sucrose, honey |
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Homocystinuria
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deficient Cystathionine synthase
accumulate homocystein and methionine Mental retardation, vessel thrombosis |
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Maple syrup urine disease
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Branched chain alpha-ketoacid dehydrogenase deficient
Accumulate leucine, valine, isoleucine and their ketoacids. Mental retardation, seizures, feeding problems, sweet smelling urine |
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McArdles' disease
type V glycogen storage disease |
Deficient muscle phosphorylase
Accumulate glycogen Glycogenosis, muscle fatigue, myoglobinuria, painful cramps, no increase in lactic acid w/ exercise |
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Phenylketonuria
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Deficient Phylalanine hydroxylase
Accumulate phenylalanine Mental retardation, microcephaly, decreased tyrosine (essential), fair skin, eczema, musty body odor (aromatic amino acids) Restrict phenylalanine, avoid artificial sweetners containing phenylalanine Autosomal recessive |
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Pompe's disease
type II glycogen storage disease |
Deficient alpha-1,4 glucosidase lysosomal enzyme
Accumulate glycogen Glycogenosis, cardiomegaly with early death |
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Von Gierke's disease
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Deficient Glucose-6-phosphatase (gluconeogenic enzyme)
Accumulate glucose-6-phosphate Glycogenosis, enlarged liver and kidneys, hypoglycemia, elevated lactate no increase in glucose w/ glucagon challenge. |
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Fragile X
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Trinucleotide repeat disorder of FMR1 gene
associated w/ chromosome breakage X-linked recessive. Mental retardation, autism. Long face, large mandible, everted ears. Macro-orchidism |
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Lesch-Nyhan Syndrome
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Deficiency of hypoxanthine-guanine phosphoribosyltranfserase
Involved in slavaging the purines hypoxanthine and guanine Excess uric acid production Mental retardation, Hyperuricemia, self-mutilation, aggression, gout, choreoathetosis X-linked recessive |
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Down's syndrome
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Trisomy 21
Mental retardation Epicanthic folds, flat facial profile, macroglossia Simian crease Risk of Hirschsprung's disease and duodenal atresia, increased risk of leukemia, Alzheimers dec AFP, inc hCG, dec urine estriol |
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Edward's syndrome
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Trisomy 18
Metal retardation. Clenched hands with overlapping fingers VSD Rocker-bottom feet Early death |
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Patau's syndrome
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Trisomy 13
Mental retardation, cleft lip and palate Polydactyl, VSD, cystic kidneys, rocker-bottom feet Early death |
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Cori cycle
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Allows lactate generated during anaerobic metabolism to undergo hepatic gluconeogenesis and become a source of glucose for muscle/RBC.
Comes at the cost of a net loss of 4 ATP/cycle |
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Irreversible enzymes of Gluconeogenesis
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Pyruvate carboxylase - in mitochondria, converts pyruvate to oxaloacetate
PEP carboxykinase - in cytosol, converts oxaloacetate to PEP Fructose 1,6 bisphosphatase - in cytosol. Fructose1,6P to F6P Glucose 6 phosphatase - in ER, G6P --> glucose only in liver, kidney, intestine only odd chain fatty acids can enter TCA cycle and gluconeogenesis via propionyl-CoA |
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Essential fructosuria
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defect in fructokinase
benign, asymptomatic fructose in blood and urine fructose does not enter cells |
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Hyperammonemia
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Aquired with liver disease or hereditary, for example w/ ornithine transcarbamoylase deficiency
Excess NH4 depletes a-ketoglutarate, leading to inhibition of TCA cycle Ammonia intoxication - tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision Rx - benzoate or phenylbutyrate to lower serum ammonia |
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Albinism
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Defects in either
1. Tyrosinase - inability to synthesize melanin from tyrosine - autosomal recessive 2. Defective tyrosine transporters - dec amounts of tyrosine, so dec melanin Can also result for lack of migration of neural crest cells. Inc risk of skin cancer. Variable inheritance due to locus heterogeneity |
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Homocysteinuria
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Three forms, all autosomal recessive
1. Cystathionine synthase deficiency Rx - Dec Met, Inc Cys, Inc B12 in diet 2. Decreased affinity of cystathionine synthase for pyridoxal phosphate Rx - Inc B6 in diet 3. Homocystein methyltransferase deficiency All forms result in excess homocystein and cysteine becomes essential. Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI). |
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Cysteinuria
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Common inherited defect of renal tubular amino acid transportor for cysteine, ornithine, lysine and arginin in PCT of kidneys
Excess cystine in urine can lead to ppt of cystine kidney stones (staghorn calculi) Rx - acetazolamide to alkalinize urine |
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Maple syrup urine disease
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Blocked degradation of branched amino acids Ile, Val, Leu due to dec alpha-ketoacid dehydrogenase.
Inc alpha-ketoacids in the blood, esp Leu CNS, defects, mental retardation, death, Urine smells like maple syrup |
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What are the functions of apolipoproteins AI, B100, CII, B48, E?
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AI - activates LCAT (esterifies cholesterol)
B100- binds to LDL receptor, mediates VLDL secretion CII - Cofactor for lipoprotein lipase B48 - Mediates chylomicron secretion E - mediates extra remnant uptake |
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Hyperchylomicronmeia
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Type 1 familial dyslipidemia
Increased chylomicrons Elevated TG, cholesterol LPL deficiency or altered CII Pancreatitis, lipema retinalis, eruptive xanthomas |
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Hypercholesterolemia
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Type IIa familial dyslipidemias
Inc LDL Elevated cholesterol Decreased LDL receptors |
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Hypertriglyceridemia
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Type IV dyslipidemia
Inc VLDL Elevated TG Hepatic overproduction of VLDL |
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Acute intermittent Porphyria
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Deficient prophobilinogen deaminase
Accumulate porphobilinogen and delta-ALA Abd pain, neurologic manifestations, urine darkens when standing No photosensitivity |
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Porphyria cutanea tarda
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Deficient uroporphyrinogen decarboxylase
Accumulate uroporphyrin (tea-colored) Abd pain, pink urine, polyneuropathy, psychologica disturbances, precipitated by drugs. Photosensitive |
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Lead poisoning
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Defective Ferrochelatase and ALA dehydratase
Accumulate coproporphyrin and delta-ALA |
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Factors that cause the Hb O2 dissociation curve to shift to the right
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Increases Cl, H+, CO2, 2,3BPG and temperature
Cause increased unloading |
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Prader Willi
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Deletion of normally active paternal allele
Mental retardation, obesity, hypogonadism, hypotonia |
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Angleman's syndrome
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Deletion of normally active maternal allele
MR, seizures, ataxia, inappropriate laughter (happy puppet) |
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Cri-du-chat Syndrome
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congenital deletion of short arm of chromosome 5
microcephaly, severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities |
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22q11 syndromes
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Cleft palate, Abnormal facies, Thymic aplasia (T cell deficiency), Cardiac defects, Hypocalcemia (parathyroid aplasia)
Microdeletion at 22q11 Variable presentation as DiGeorge's (thymic, parathyroid, cardiac) or velocardiofacial (palate, facial, cardiac) |