Biochemistry Flashcards
1
Q
What is Chediak-Higashi syndrome?
A
microtubule polymerization defect (impaired phagosome-lysosome fusion) resulting in decreased phagocytosis –> recurrent pyogenic infections, partial albinism, peripheral neuropathy
2
Q
What is Kartagener’s syndrome?
A
immotile cilia due to a dynein arm defect in cilia; results in male and female infertility (sperm immotile), bronchiectasis and recurrent sinusitis (bacteria and particles are not pushed out) and associated with situs inversus
3
Q
Where are the cytoskeletal elements actin and myosin found?
A
microvilli, muscle contraction, cytokinesis, adherens junctions
4
Q
Where are microtubules found?
A
cilia, flagella, mitotic spindle, neurons, centrioles
5
Q
Where are intermediate filaments found?
A
vimentin, desmin, cytokeratin, GFAP, neurofilaments
6
Q
What does vimentin stain?
A
connective tissue
7
Q
What does desmin stain?
A
muscle
8
Q
What does cytokeratin stain?
A
epithelial cells
9
Q
What does GFAP stain?
A
neuroglia
10
Q
What does neurofilaments stain?
A
neurons
11
Q
type 1 collagen
A
bone, skin, tendon, dentin, fascia, cornea, late wound repair
12
Q
type 2 collagen
A
cartilage (including hyalin), vitreous body, nucleus pulposus
13
Q
type 3 collagen (reticulin)
A
skin, blood vessels, uterus, fetal tissue, granulation tissue
14
Q
type 4 collagen
A
basement membrane or basal lamina
15
Q
What are the steps for collagen synthesis and structure?
A
Inside the fibroblast
- translation of the collagen alpha chains (preprocollagen) in the RER
- hydroxylation of proline and lysine residues (requires vitamin C)
- glycosylation of pro-alpha-chain lysine residues and formation of procollagen in the ER
- exocytosis of procollagen into extracellular space
Outside fibroblast
- cleavage of termina, regions of procollagen –> insoluble tropocollagen
- cross-linkage of tropocollagen to make collagen fibrils
16
Q
What is Ehlers-Danlos syndrome?
A
faulty collagen synthesis causing:
- hyperextensible skin
- easy bruising
- hypermobile joints
17
Q
What is osteogenesis imperfecta?
A
genetic bone disorder (brittle bone disease), most common form is AD with abnormal type 1 collagen causing:
- multiple fractures with minimal trauma
- blue sclerae due to translucency of the connective tissue over the choroid
- hearing loss (abnormal middle ear bones)
- dental imperfections (lack of dentin)
18
Q
What is Albort’s syndrome?
A
abnormal type IV collagen; most common form is X-linked recessive
Characterized by: progressive hereditary nephritis and deafness, can be associated with ocular disturbances
Note: type 4 is important for basement membrane of kidney, ears and eyes
19
Q
What are the characteristics of Prader-Willi syndrome?
A
Results from deletion of normally active paternal allele on chromosome 15
mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
20
Q
What are the characteristics of Angelman’s syndrome?
A
Deletion of the normally active maternal allele on chromosome 15
mental retardation, seizures, ataxia, inappropriate laughter
21
Q
What is Leber’s hereditary optic neuropathy?
A
mitochondrial myopathy through mitochondrial inheritance
degeneration of retinal ganglion cells and axons –> acute loss of central vision
22
Q
What is achondroplasia?
A
Autosomal-dominant disease
cell signaling defect of FGF receptor 3 –> dwarfism, short limbs (but head and drunk are normal size); associated with advanced paternal age
23
Q
What is autosomal-dominant polycystic kidney disease?
A
always bilateral!! massive enlargement of the kidneys due to multiple large cysts, associated with APKD1
presents with flank pain, hematuria, hypertension, progressive renal failure
associated with polycystic liver disease, berry aneurysms, berry aneurysms, mitral valve prolapse
24
Q
What is familial adenomatous polyposis?
A
autosomal dominant; colon covered with adenomatous polyps –> colon cancer later on
mutation in chromosome 5 (APC gene)
25
What is familial hypercholestolemia?
autosomal dominant; elevated LDL due to defective LDL receptor
associated with severe atherosclerotic disease, tendon xanthomas, MI before age 20
homozygotes ~700mg/dL
26
What is hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
autosomal dominant; inherited disorder of blood vessels
findings: telangiectasia, recurrent epistaxis, skin discolorations, AVMs
27
What is hereditary spherocytosis?
autosomal dominant; spheroid erythocytes due to spectrin or ankyrin defect; hemolytic anemia; increased MCHC
splenectomy is curative
28
What is Huntington's disease?
autosomal dominant; decreased levels of GABA and ACh --> depression, progressive dementia, choreiform movements, caudate atrophy
gene located on chromosome 4; CAG repeats
29
What is Marfan's syndrome?
autosomal dominant disease; fibrillin gene mutation --> connective tissue disorder affecting skeleton, heart and eyes
findings: tall with long extremities, pectus excavatum, hyperextensive joints, and long tapering fingers and toes, cystic medial necrosis of aorta --> aorta incompetence and dissecting aortic aneurysms; floppy mitral valve and subluxation of lenses
30
Neurofibromatosis type 1 (von Recklinghausen's disease)
autosomal dominant disease
findings: cafe au lait spots, neural tumors, Lisch nodules, skeletal disorders (eg scoliosis) and optic pathway gliomas
on long arm of chromosome 17
31
Neurofibromatosis type 2
autosomal dominant disease
| bilateral acoustic schwannomas, juvenile cataracts. NF2 gene on chromosome 22
32
tuberous sclerosis
autosomal dominant disease
findings: facial lesions, hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental redardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas
incomplete penetrance, variable presentation
33
von Hippel-Lindau disease
autosomal dominant disease
findings: hemangioblastomas of retina/cerebellum/medulla; half develop mutliple biolateral renal cell carcinomas and other tumors
associated with VHL gene (tumor suppression) and chromosome 3(3p) --> constitutive expression of HIF (transcription factor) and activation of angiogenic GFs
34
What are the autosomal recessive diseases?
abinism, ARPKD (infantile polycystic kidney disease), cystic fibrosis, glycogen storage disease, hemochromatosis, mucopolysaccharidoses, phenylketonuria, sickle cell anemias, sphingolipidoses, thalassemia
35
cystic fibrosis
autosomal recessive defect in CFTR gene (chromosome 7); CFTR channel secretes Cl- in lungs and GI tract and actively absorbs Cl- from sweat
mutation causes abnormal protein folding --> degradation of channel before reaching cell surface
defective channel --> secretion of abnormally thick mucus that plugs lungs, pancreas and liver --> recurrent pulmonary infections, chronic bronchitis, bronchiectasis, pancreatic insufficiency, meconium ileus in newborns
causes infertility in males due to bilateral absence of vas deferences, fat-soluble vitamin deficiencies, failure to thrive in infancy
36
X-linked recessive disorders
Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry's disease, G6P deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne's muscular dystrophy, Hunter's Syndrome, Hemophilia A and B
"Be Wise, Fool's GOLD Heeds Silly Hope"
37
Duchenne's muscular dystrophy
X-linked frame-shift mutation --> deletion of dystrophin gene --> accelerated muscle breakdown
Weakness, pseduohypertrophy of calf muscles (due fibrofatty replacement of muscle), cardiac myopathy, use of Gowers manuever
38
Becker's muscular dystrophy
X-linked mutated dystrophin gene; less severe than Duchenne's; onset in adolescence or early adulthood
39
Fragile X syndrome
X-linked defect affecting methylation and expression of the FMR1 gene
findings: macro-orchidism, long face with a large jaw, large everted ears, autism, mitral valve prolapse
CGG repeats
40
Trinucleotide repeat expansion diseases
CAG: Huntington's
CTG: Myotonic dystrophy
CGG: Fragile X Syndrome
GAA: Friedreich's ataxia
41
Down's Syndrome
Trisomy 21
Findings: mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between 1st 2 toes, duodenal atresia, congenital heart disease, associated with increased risk of ALL and Alzheimer's disease
pregnancy screen: decreased AFP, decreased estriol, increased B-HCG, increased inhibin A, ultrasound shows increased nuchal translucency
42
Edwards' syndrome
trisomy 18
findings: severe mental retardation, rocker-bottom feet, micrognathia, low-set ears, clenched hands, promient occiput, congenital heart disease
death occurs within 1 year of birth
43
Patau's syndrome
trisomy 13
findings: severe mental retardation, rocker-bottom feet, microphtalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactylyl, congenital heart disease
death usually occurs within 1 year of birth
44
Robertsonian translocation
nonreciprocal chromosomal translcation that most commonly involves pairs 13, 14, 15, 21, 22 --> long arms of the 2 acrocentric chromsomes fuse at the centromere and the 2 short arms are lost
45
Cri-du-chat syndrome
congential microdeletion of the short arm of chromosome 5 (46, XX or XY, 5p-)
findings: microcephaly, moderate to severe mental retardation, high pitched crying, epicanthal folds, cardiac abnormalities
46
Williams syndrome
congenital microdeletion of long arm of chromosome 7
findings: distinctive "elfin" facies, mental retardation, hypercalcemia (increased sensitivity to vitamin D), well developed verbal skills, extreme friendliness to strangers, cardiovascular problems
47
DiGeorge syndrome
deue to aberrant development of 3rd and 4th brachial pouches
thymic, parathyroid and cardiac defects
48
Velocardiofacial syndrome
due to aberrant development of 3rd and 4th brachial pouches
palate, facial and cardiac defects
49
Vitamin A (retinol)
fat soluble vitamin
antioxidant, used for visual pigments, normal differentiation of epithelial cells
deficiency: night blindness
excess: arthralgias, fatigue, headaches, skin changes, sore throat, alopecia, teratogenic (cleft palate, cardiac abnormalities)
50
Vitamin B1 (thiamine)
Water soluble vitamin
Fxn: in thaimine pyrophosphate (TPP), a cofactor for 1. pyruvate dehydrogenase (glycolysis), alpha-ketoglutarate dehydrogenase (TCA), transketolase (HMP shunt), branched chain AA dehydrogenase
Deficiency: impaired glucose breakdown --> ATP depletion (brain and heart affected first), Wernicke-Korsakoff syndrome and beriberi
51
Vitamin B2 (riboflavin)
water soluble vitamin (redox reactions)
Fxn: cofactor in redox rxns
Deficiency: cheilosis, corneal vascularization "2C's"
52
vitamin B3 (niacin)
water soluble vitamin
Fxn: constituent of NAD+, NADP+ (redox reactions)
Deficiency: pellagra (3D's- diarrhea, dermatitis, dementia)
Excess: facial flushing
53
Vitamin B5 (pantothenate)
water soluble vitamin
Fxn: essential component of CoA and fatty acid synthase
Deficiency: dermatitis, enteritis, alopecia, adrenal sufficiency
54
Vitamin B6 (pyridoxine)
Water soluble vitamin
Fxn: converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation reactions, glycogen phosphorylase, cystathionine synthesis, and heme synthesis
deficiency: convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia
55
Vitamin B12 (cobalamin)
water soluble vitamin
Fxn: cofactor for homocysteine methyltransferase (transfers CH3 groups to methylcobalamin) and methylmalonyl-CoA mutase
Deficiency: macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms
Note: found in animal products, synthesized by microorganisms, LARGE reserve pool in the liver
56
Folic acid
Water soluble vitamin
Fxn: converted to THF (one carbon transfer methylation reactions) which is important for DNA and RNA synthesis
Deficiency: macrocytic, megaloblastic anemia but no neurologic symptoms
57
S-adenosyl methionine
ATP + methionine = SAM
SAM transfers methyl units
Regeneration of methionine requires vitamin B12 and folate
58
Biotin
Cofactor for carboxylation enzymes (which add a 1-carbon group): 1. pyruvate carboxylase, acetyl-coa carboxylase, propionyl-coa carboxylase
deficiency: rare, dematitis, alopecia, enteritis
59
Vitamin C (absorbic acid)
Fxn: antioxidant; also 1. facilitates iron absorption 2. hydroxylation of proline and lysine in collagen synthesis 3. dopamine beta-hydroxylase which converts DA to NE
deficiency: scurvy- swollen gums, bruising, hemarthrosis, anemia, poor wound healing, WEAKENED immune response
60
Vitamin D
fat soluble vitamin
Fxn: increase intestinal absorption of calcium and phosphate, increased bone resorption
deficiency: rickets in children, osteomalacia in adults, hypocalcemic tetany
excess: hypercalcemia, hypercalciuria, loss of appetite, stupor
61
vitamin E
fat soluble vitamin
Fxn: antioxidant (protects erythrocytes and membranes)
deficiency:increased fragility of erythrocytes (hemolytic anemia), muscle weakness, posterior column and spinocerebellar tract demyelination
62
vitamin K
fat soluble vitamin
fxn: catalyzes carboxylation of glutamic acid residues for blood clotting, made by intestinal flora
deficiency: neonatal hemorrhage with increased PT and PTT but normal bleeding time
necessary for clotting factors 2, 7, 9, 10, protein C and S
note: warfarin is a vitamin K antagonist
63
zinc
fxn: impt for activity of 100+ enzymes (zinc fingers for the TF)
deficiency: delayed wound healing, hypogonadism, decreased adult hair, dysgeusia, anosmia
64
Kwashiorkor
protein malabsorption --> skin lesions, edema, liver malfunction "small child with big belly"
MEAL: malnutrition, edema, anemia, liver (fatty)
65
Marasmus
energy malnutrition --> tissue and muscle wasting, loss of subcutaneous fat, and variable edema
66
Name examples of activated carriers.
Phosphoryl, electrons, acyl, CO2, 1 carbon units, CH3, aldehydes
67
What are the 5 cofactors for the pyruvate dehydrogenase complex?
1. pyrophosphate (B1)
2. FAD (B2)
3. NAD (B3)
4. CoA (B5)
5. lipoic acid
reaction: pyruvate + NAD + CoA --> Acetyl CoA + CO2+ NADH
68
How do electron transport inhibitors work?
directly inhibit e transport causing decreased proton gradient and blocking of atp synthesis
ie rotenone, CN-, antimycin A, CO
69
How do ATPase inhibitors work?
directly inhibit mitochondrial ATPase, causing increase proton gradient but no ATP is produced bc e transport stops
ie oligomycin
70
How do uncoupling agents work?
increase permeability of membrane, causing a decreased proton gradient and increased O2 consuption; atp synthesis stops but e transport continues; PRODUCES HEAT!
ie 2,4-DNP, aspirin
71
What are the irreversible enzymes involved in gluconeogenesis?
1. pyruvate carboxylase (pyruvate --> oxaloacetate)
2. PEP carboxykinase (oxaloacetate --> phosphoenolpyruvate)
3. fructose-1,6-bisphosphatase (f-1,6-BP --> f-6-p)
4. glucose-6-phosphatase (G6P --> glucose)
Pathway Produces Fresh Glucose
found mostly in the liver, but also found in the kidney and intestinal epithelium
72
What is the purpose of the HMP shunt?
to provide a source of NADPH (reductive rxns), ribose for nucleotide synthesis and glycolytic intermediates
73
What is chronic granulomatous disease?
NADPH oxidase deficiency
WBCs of pts can utilize H2O2 made by invading organisms and convert it to ROIs, but are at increased infection by catalase-positive organisms since they neutralize their own H2O2
74
What is G6P dehydrogenase deficiency?
X-linked recessive disorder
G6P dehydrogenase is necessary to convert NADP+ to NADPH, which is needed to keep GSH reduced, which is needed to convert hydrogen peroxide to water
Without this enzyme in RBCs, they undergo hemolytic anemia due to poor RBC defense against oxidizing agents
Smear can show Heinz bodies (oxidized hg precipitated) and bite cells (phagocytic removal of the Heinz bodies by macrophages)
75
essential fructosuria
defect in fructokinase (fructose --> f-1-p); autosomal recessive but benign, asymptomatic
symptoms: fructose in blood and urine
76
fructose intolerance
heriditary deficiency of aldolase B (fructose-1-p --> dihydroxyacetone-P or glyceraldehyde)
results in increased f-1-p --> decreased available phosphate --> inhibition of glycogenolysis and gluconeogenesis
symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
tx: decrease intake of fructose and sucrose (glucose + fructose)
77
galactokinase deficiency
hereditary deficiency of galactokinase (galactose --> galactose-1-p)
since it cant be converted, aldose reductase converts galactose to galactitol which accumulates
symptoms: galactose in blood and urine, infantile cataracts
78
classic galactosemia
absence of g-1-p uridyltransferase (galactose-1-p --> glucose-1-p) causing accumulation of toxic substances
symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
tx: exclude galactose and lactose from diet
79
glucogenic amino acids
methionine, valine, arginine, histidine
80
glucogenic/ketogenic amino acids
isoleucine, phenylalanine, threonine, tryptophan
81
ketogenic amino acids
leucine, lysine
82
acidic amino acids
aspartate and glutamine
83
basic amino acids
arginine, lysine and histidine
84
What is the result of hyperammonemia?
excess NH4+ depletes alpha-ketoglutarate --> inhibition of TCA
intoxication: tremor, slurring, somnolence, vomiting, cerebral edema, blurring of vision
85
What is OTC deficiency?
most common urea cycle disorder that is X-linked recessive
interferes with the bodys ability to eliminate ammonia, excess carbamoyl phosphate is converted to orotic acid (pyrimidine synthesis pathway)
findings: orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
86
phenylketonuria
decreased phenylalanine hydroxylase (phenylalanine --> tyrosine) or THB cofactor leading to excess pheylketones in the urine
findings: mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor
tx: decreased phenylalanine and increased tyrosine in diet
87
aklaptonuria
congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine; autosomal recessive
findings: dark connective tissue, brown sclera, black urine, debiltating arthralgias
88
albinism
tyrosinase deficiency (cant make melanin from tyrosine; AR) or defective tyrosine transporters (decreased amounts of tyrosine) or lack of migration of neural crest cells
89
homocystinuria
1. cystathionine synthase deficiency (converts homocysteine to cystathionine using B6) which the tx is decreased met and increased cys, b12, and folate
2. decreased affinity of cystathionine synthase for B6 (tx is increased vitamin b6 in diet)
3. homocysteine methytransferase deficiency
findings: increased homocysteine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis
90
cystinuria
dfect of renal tubular amino acid transporter for cysteine, ornithine, lysine and arginine in the PCT of the kidneys ---> excess cysteine can cause kidney stones
91
Hartnup disease
AR disease; defective neutral amino acid transporter on renal and intestinal epithelial cells --> tryptophan excretion in urine and decreased absorption in gut --> pellagra
92
Von Gierke's disease
glycogen storage disease
deficient enzyme- glucose-6-phosphatase (G6p --> glucose) causing severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate and hepatomegaly
93
Pompe's disease
glycogen storage disease
deficient enzyme- lysosomal alpha-1,4- glucosidase causing cardiomegaly and system findings leading to early death
94
Cori's disease
glycogen storage disease
deficient enzyme- debranching enzyme causing milder form of Von Gierke's disease with normal blood lactate levels
95
McArdle's disease
glycogen storage disease
deficient enzyme- skeletal muscle glycogen phosphorylase causing increased glycogen in muscle, but cant break it down, leading to painful muscle cramps, myoglobinuria with exercise
96
Fabry's disease
lysosomal storage disease (sphingolipidoses)
deficient enzyme- alpha galactosidase A (ceramide trihexoside --> glucocerebroside) causing increased ceramide trihexoside
findings: peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease
XR inheritance
97
Gaucher's disease
lysosomal storage disease (sphingolipidoses)
deficient enzyme- beta glucocerebrosidase (glucocerebroside --> ceremide) causing increased glucocerebroside
findings: hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells
AR inheritance
98
Niemann-Pick disease
lysosomal storage disease (sphingolipidoses)
deficient enzyme- sphingomyelinase (sphingomyelin --> ceremide) causing increased sphingomyelin
findings: progressive neurodegeneration, hepatosplenomegaly, cherry red spot on the macula, foam cells
AR inheritance
"No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase)"
99
Tay-Sachs
lysosomal storage disease (sphingolipidoses)
deficient enzyme- hexoaminidase A (GM2 --> GM3) so GM2 ganglioside accumulates
findings: progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, NO hepatosplenomegaly
AR inheritance
"Tay-SaX lacks heXosaminidase"
100
Krabbe's disease
lysosomal storage disease (sphingolipidoses)
deficient enzyme- galactocerebrosidase (galactocerebroside --> ceramide) so galactocerebroside accumulates
findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells
AR inheritance
101
metachromatic leukodystrophy
lysosomal storage disease (sphingolipidoses)
deficient enzyme- arylsulfase A (sulfatide --> galactocerebroside) so sulfatide accumulates
findings: central and peripheral demyelination with ataxia, dementia
AR inheritance
102
Hurler's syndrome
lysosomal storage disease (mucopolysaccharidoses)
deficient enzyme - alpha-L-iduronidase
accumulated substrate- heparan sulfatte, dermatan sulfate
findings: developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
AR inheritance
103
Hunter's syndrome
lysosomal storage disease (mucopolysaccharidoses)
deficient enzyme- iduronate sulfatase causing increased heparan sulfate, dermatan sulfate
findings: milder Hurler's + aggressive behavior, no corneal clouding
XR inheritance
"HUNTERS see clearly (no corneal clouding) and aim for the X (X-linked recessive)
104
Apo A-1
activates LCAT
105
Apo B-100
binds LDL receptor, mediates VLDL secretion
106
Apo C-2
cofactor for LDL
107
Apo B-48
mediates chylomicron secretion
108
Apo E
mediates extra (remnant) uptake
109
Type 1 dyslipidemia (hyperchylomicronemia)
LPL defiency or altered Apo C-2
increased chylomicrons, elevated TG and cholesterol
pancreatitis, hepatosplenomegaly, eruptive xanthomas (no athlerosclerosis)
110
Type 2A dyslipidemia (familial hypercholesterolemia)
AD due to absent or decreased LDL receptors --> accelerated atherlosclerosis, tendon (Achilles) xanthomas, and corneal arcus
Increased LDL, elevated cholesterol
111
Type 4 dyslipidemia (hypertriglyceridemia)
hepatic overproduction of VLDL --> pancreatitis
increased VLDL, TG
112
abetalipoproteinemia
hereditary (AR) inability to synthesize lipoprotiens due to deficiencies in apoB-100 and apoB-48
accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons
findings: failure to thrive, steatorrhea, acanthocytosis (spur cells), ataxia, night blindness
