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322 Cards in this Set
- Front
- Back
- 3rd side (hint)
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I cell disease
|
(-) mannose-6-P addition to lysosomal enzymes
enzymes secretedinto the extracellular space increased plasma enzymes coarse face, dec. joint ROM, FATAL |
inclusion cell disease
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Microtubule drugs
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mebednazole
griseofulvin vincristine pactaxel colchicine |
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Chediak Higashi
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defective MT depolarization
decreased phagocytosis recurrent pyogenic infection albinism peripheral neuropathy |
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Wright's stain
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WBCs, chromosomes
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Silver stain
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Pseudomonas, Legionella
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Collagen I
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bone, skin, tendon, dentin
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Collagen II
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cartilage
osteogenesis imperfecta (I, II) |
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Collagen III
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wound granulation, vessels, skin, uterus, fetus,
Ehlers Danlos (III) |
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Collagen IV
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basement membrane
Alport's (IV) |
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Ehlers Danlos
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defective cleavage of procollagen III
dec collagen III hyperextensible skin, joints autoD,r berry aneurysm joint dislocation organ rupture |
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osteogenesis imperfecta
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defect pro-alpha collagen I, II glycosylation
multiple fractures blue sclera hearing loss malformed teeth (-) II = intrauterine fatality |
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Alport's syndrome
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(-) collagen IV
Xr progressive nephritis deafness ocular disturbance |
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Marfan's
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(-) fibrillin
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Hardy Weinberg
Xr disease in males |
q
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Hardy Weinberg
Xr disease in females |
q2
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Prader Willi
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deletion of PATERNAL chr 15 gene
MR hyperphagia, obesity hypogonadism hypotonia |
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Angelman's syndrome
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deletion of MATERNAL chr 15 gene
MR "happy puppet" inappropriate laughter seizures |
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Achondroplasia gene
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FGF3
advanced paternal age |
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APKD gene
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APKD1 / chr 16
adult polycystic kidney always BILATERAL autoD mitral valve prolapse berry aneurysm |
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Familial adenomatous polyposis
(FAP) |
APC/ 5
ademantous polyps after puberty |
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Familial hyperlipidemia IIA
|
defective, absent LDL R
homozygotes >700 chol tendon zanthomas severe atherosclerosis early MI |
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Hereditary hemorrhagic telangiectasia
Osler-Weber_rendu |
disorderly vessels
AVM telangiectasia epsitaxis skin discoloration |
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Hereditary spherocytosis
|
(-) spectrin, ankyrin
Rx splenectomy |
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Huntington's
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(CAG)n , / 4
"hunting 4 food" anticipation dec. GABA, ACh depression, progressive dementia, chorea |
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MEN II, III
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ret
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Neurofibromatosis I
von recklinghausens' |
NF1/17
cafe au lait spots neural tumors Lisch nodules--pigmented harmatomas pheochromocytoma optic gliomas |
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Neurofibromatosis II
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NF2/22
bilateral acoustic neuroma juvenile cataracts |
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Tuberous sclerois
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adenoma sebaceum
ash leaf skin lesion renal cysts, angiomyolipoma harmartoma MR seizure |
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Von hippel-Lindau disease
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(-)VHL/3, tumor supressor
constitutive expression of HIF transcription factor hemangioblastoma of retina/CNS bilateral RCC |
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Cystic fibrosis
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auto r
CFTR gene/7 pseudomonas, S aureus URI |
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Duchenne's
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(-) dystrophin
X-linked frame shift acceleratied muscle breakdown pseudohypertrophy of calf muscles (fibrofatty replacement) Gower's maneuver onset < 5yo |
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Becker's
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mutated dystrophon, less severe than Duchene's
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Fragile X
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(CGG)n , affects methylation and expression of FMR1 gene
MR, macroorchidism, large jaw, autism |
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Trinucleotide repeat diseases
|
Huntington (CAG)
Myotonic dystrophy (CTG)n Fragile X (CGG)n Friedriech's ataxia (GAA)n |
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Edward's
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trisomy 18
rockerbottom feet micrognathia clenched hands congentialHD death within 1 yr |
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Patau's
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trisomy 13
microcephaly microophthalmia cleft lip/palae holoprosencephaly polydactyly |
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Cri du chat
|
5p-
microcephaly, high pitched cry, epicanthal folds, congHD |
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Digeorge's
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22q11,
3rd, 4th branchial pouch |
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B1 deficieny
|
wet beriberi- HO CHF, dilated cmpthy
dry beriberi-poly neuritis, symm. muscle wasting Wernike-Korsakoff |
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B2 deficiency
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cheliosis, cornial vascularization
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B3 deficiency
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glossitis, pellargra
Pellagra: (D, dermatitis, dementia) |
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B5 deficiency
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dermatitis,
enteritis , alopecia adrenal insufficiency |
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B6 deficiency
|
seizure
irritability peripheral neuopathy indicible by INH, OC |
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B12 deficiency
|
macrocytic megaloblastic anemia
CNS sx (abn myelin) |
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Folate deficiency
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macrocytic megaloblastic anemia
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E deficiency
|
hemolytic anemia
|
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K deficiency
|
inc PT, inc aPTT , nl bleeding time
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Glycolysis RLS
|
phosphofructokinase-1
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Gluconeogenesis RLS
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fructse bis-Pase-2
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TCA cycle
|
isocitrate dehydrogenase (?)
|
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Glycogen synthesis
|
glycogen synthase
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Glycogenolysis
|
Glycogen phosphorylase
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HMP shunt
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glucose-6-P dehydrogenase
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denovo pyrimidine synthesis
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aspartate transcarmoylase
|
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De novo purine synthesis
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Glutamine-PRPP amidotransferase
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Urea cycle
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carbamoyl phosphate synthetase
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Fatty acid synthesis
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acetyl CoA carboxylase
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Ketogenesis
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HMGCoA synthase
|
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Cholesterol synthesis
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HMG CoA reductase
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B1 cofactor
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thiamine pyrophosphate (TPP)
pyruvate dehydrogenase (glycolysis) alpha ketoglutarate dehydrogenase (TCA) transketolse (HMP shunt) Branched charin AA dehydrogenase |
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B2 cofactor
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FADH2
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B3 cofactor
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NAD, NADP
derived from tryptophan |
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B5 cofactor
|
acyl transferase reaction, component of CoA
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B6 cofactor
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transamination, decarboxylation, glycogeon phosphoylase, heme synthesis, niacin (B3)synthesis
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B12 cofactor
|
homocystene methyltransferase
methylmalonyl CoA mutase |
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Folate
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1 carbon transfers, methylation
DNA/RNA base synthesis |
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Biotin
|
carboxylation
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C cofactor
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keeps Fe2+ reduced, collagen snythesisi,
dopamine conversion to NE by dopamine beta hydroxylase |
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K cofactor
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gamma carboxylation of glutamic acid residus
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HPCC
DNA repair problem |
Mismatch repair
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Zeroderma pigmentosum
|
Nucelotide excision repair prevents repair of thymidine dimers
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Stop codons
|
UGA U go away
UAA U are away UAG U are gone |
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RNA poly I makes...
II III |
rRNA
mRNA tRNA (eukaryotes) Prokaryotes have 1 RNA polymerase complex that makes all 3 rna types. |
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snRNP
|
spliceosome
splices of pre-mRNA |
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transmitted through both parents
ALL females of affected father are diseased every generation effected |
XD
|
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transmitted through mother only
normal offspring from affected father |
Mt inheritence
|
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Achondroplasia
-inheritance -affected gene |
AD
FGF3 advanced paternal age nl head, trunk; short limbs |
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APKD
-inheritance -affected gene/chr |
AD
APKD 1 chr 16 pckd, berry anerusym, mitral valve prolapse |
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Familial adenomatous polyposis
-inheritance -affected gene/chr |
AD
APC/5 |
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Familial hypercholesterolemia
-hyperlipidemia IIA -inheritance -affected gene/chr |
AD
LDLR homozygotes >700mg/dl cholesterol tendon xanthomas, early MI |
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Osler-Weber-Rendu
|
AD
Hereditary hemorrhagic telangectasia |
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Osler-Weber-Rendu
Hereditary hemorrhagic telangectasia -inheritance -problem |
AD
disorderly blood vessels telangectasias arteiovenous malformation epistaxis skin discoloration |
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Hereditary spherocytosis
-inheritance -affected gene/chr |
AD
spectrin or ankyrin |
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Huntington Disease
-inheritance -affected gene/chr |
AD
(CAG)n/4 "hunting 4 food" depression, progressive dementia caudate atrophy, low GABA, Ach in caudate, chorea |
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Marfan's
-inheritance -affected gene/chr |
AD
fibrillin tall, pectus excavatum, hyperextensive joints, arachnodactyly, aortic dissection, follpy mitral valve, lens sublux. |
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Men II, III
|
AD
ret familial endocrine tumors |
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Von Recklinghausen disease
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neurofibromatosis 1
|
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Neurofibromatois 1
vonRecklignhausen -inheritance -affected gene/chr |
AD
NF1/17 cafe au lait, neural tumors, Lisch harmatoma nodules in iris, scoliosis, optic gliomas, phoechromocytoma |
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Neurofibromatosis 2
-inheritance -affected gene/chr |
AD
NF2/22 bilateral acoustic neuromas, juvenile cataracts |
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Tuberous sclerosis
-inheritance -symptoms |
AD
"ash-leaf" Angiolipomas, cyst (renal) Seizures Harmatomas Low IQ (MR) Encomplete penetrance Adenoma sebaceum Fall, ash leaf |
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Von Hippel Lindau
-inheritance -affected gene/chr |
AD
VHL/3 VHL tumor suppressor--> HIF--> angiogenic growth factors hemangioblastoma of retina, cerebellum, medulla bilateral RCC |
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Cystic fibrosis
-inheritance -affected gene/chr |
Ar
- Phe508/ 7 defected Cl- channel |
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X-linked recessive
|
Be Wise Fool's GOLD Heeds False Hope
Bruton's agammaglobulinemia Wiskott-Aldrich syndrome Fragile X G6PD def Ocular albinism Lesh Nyhan Duchenne's/Becker MD Hemophilia A,B Fabry's Hunter's |
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Duchenne's
-inheritance -affected gene/chr -problem -sx |
X-linked recessive
-DMD gene for dystrophin muscle degeneration pelvic girdle weakness progressive superiorly fibrofatty calf pseudohypertrophy Gower's manuver onset <5yo increased CK |
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Becker's
-inheritance -affected gene/chr -problem -sx |
X-linked recessive
mutated DMD, dystrophin mild muscular degeneration adolensent/YA onset less severe than Duchenne's |
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Fragile X
-inheritance -affected gene/chr -problem -sx |
X linked recessive
FMR1 gene chromosomal breakage (CGG)n macroorchidism, large jaws and ears, autism |
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Trinucelotide repeats
|
Huntington
myotonic dystrophy Fragile X Friedrich's ataxia |
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Trinucleotide repeat
Huntington myotonic dystrophy Fragile X Friedrich's ataxia |
Huntington = CAG
myotonic dystrophy = CTG Fragile X= CGG Friedrich's ataxia = GAA |
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Down's syndrome
-genetic problem -Dx -symptom |
trisomy 21
Dx: low AFP high HcG low estridiol high inhibin A nuchal translucency on US flat faciese,s peidcanthal folds, simian crease, 1/2 toe gap, duodenal atresia, congenital HD, ASD, risk of ALL and alzhemier's |
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Edward's syndrome
-genetic defect -symptoms |
trisomy 18
MR rockerbottom feet micrgnathia clenched hands congenital HD death by 1 yr |
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Patau's syndrome
-genetic defect -symptoms |
trisomy 13
severe MR rocker-bottom feeth microphthalmia microcephaly cleft lip/palate holoprosencephaly polydactyly congenital HD death by 1yr |
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Robertsonian translocation
|
2 long arms of acrocentrc chromosomes (centromeeres near tips) fuse
loss of tiny short arms Balanced= asymptomatic Unbalanced= downs, pataus, miscarriafge, stillbirth... |
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Chromosomal inversion
-pericentric -paracentric |
chromosome segment reversed end to end
reduced fertility pericentric involves centromere, proceeds through meiosis paracentric does not include centromere, does not proceed through meiosis |
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Cri-du-chat
-genetic defect -symptoms |
5p- deletion
microcephaly MR high pitch cry epicanthal folds cardiac abnormalities |
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William's syndrome
-genetic defect -symptoms |
7q - deletion
elastin elfin facies MR well developed verbal skills, cheerful, extreme friendliness with strangers, CV problems |
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22q 11 deletion
|
apperant development of 3rd and 4th branchial pouch
"CATCH-22" Clef palate, Abn facies, Thymic aplasia/T cell deficiency, Cardiac defects, Hypocalcemia fromparathyroid aplasia 22q11 -DiGeorge's -Velocardiofacial syndrome |
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Hartnup Disease
|
impaired tryptophan absorption
pellagra diarrhea dermatitis dementia |
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Trinucleotide repeat
Huntington myotonic dystrophy Fragile X Friedrich's ataxia |
Huntington = CAG
myotonic dystrophy = CTG Fragile X= CGG Friedrich's ataxia = GAA |
|
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|
Down's syndrome
-genetic problem -Dx -symptom |
trisomy 21
Dx: low AFP high HcG low estridiol high inhibin A nuchal translucency on US flat faciese,s peidcanthal folds, simian crease, 1/2 toe gap, duodenal atresia, congenital HD, ASD, risk of ALL and alzhemier's |
|
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|
William's syndrome
-genetic defect -symptoms |
7q - deletion
elastin elfin facies MR well developed verbal skills, cheerful, extreme friendliness with strangers, CV problems |
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Hartnup Disease
|
impaired tryptophan absorption
pellagra diarrhea dermatitis dementia |
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Urea cycle RLS
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carbamoyl phosphate synthetase
|
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Fatty acid synthesis RLS
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acetyl coA carboxylase
|
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Fatty acid oxidation RLS
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carnitine acyltransferase I
|
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Ketogenesis RLS
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HMG CoA synthase
|
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Cholesterol synthesis RLS
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HMG CoA reductase
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Glycolysis RLS
|
PFK1
|
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Gluconeogenesis RLS
|
Fructose bisphosophatasase 2
|
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TCA cycle RLS
|
isocitrate dehydrogenase
|
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Glycogen snythesis RLS
|
glycogen synthase
|
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Glycogenolysis RLS
|
Glycogen phosphorlyase
|
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HMP shunt RLS
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glocase 6 phosphate dehydrogenase
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de novo pyrimidine synthesis RLS
|
aspartate transcarbamoylase (ATCase)
|
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de novo purine synthesis RLS
|
glutamine-PRPP amidotransferase
|
|
|
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(-) pyruvate kinase
|
hemolytic anemia
inability to maintain Na/K ATPase Na in--> RBC swelling, lysis |
|
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(-) pyruvate dehydrogenase
|
congenital lactic acidosis
|
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(-) pyruvate carboxylase
|
hypoglycemia
|
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(-) PEP carbokinase
|
hypoglycemia
|
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(-) F 1,6, BP
|
hypoglycemia
|
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(-) glucose-6-phosphatase
|
hypoglycemia
|
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(-) glucose-6-phosphate dehydrogenase
|
G6PD deficiency
increased ROS hemolytic anemia (+ fava beans, sulfa drugs, antimalarials, primaquine) |
|
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(-) aldose B
|
fructose intolerance
fructosuria hypoglycemia cirrhosis |
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(-) fructokinase
|
benign fructosuria
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(-) galctose 1P-UDT
|
classic galactosemia
cataracts, MR, jaundice, failure to thrive |
|
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(-) galactose kinase
|
mild sx of galactosemia
cataracts, MR |
|
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(-) NADPH oxide
|
chronic granulomatous disease
|
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(-) ornithine transcarbamoylase
|
failure to synthesis urea
hyperammoniemia MR |
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(-) phenalanine hydroxylase
|
PKU
|
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(-) THB4/biopterin factor
|
PKU
|
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Glut 1
|
RBC, brain
|
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Glut 2
|
kidney, liver, beta cell
|
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Glut 3
|
brain, neuron
|
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Glut 4
|
muscle, adipose
insulin sensitive |
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Glut 5
|
fructose
small intestine, testes |
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NADPH
|
product of HMP shunt
used in synthesis reactions respiratory burst P450 |
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arsenic
|
inhibits glyceradehyde-3-P
complexes with lipoic acid decreases ATP |
|
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Gluconeogeneis irreversible enzymes
|
"pathway produces fresh glucose"
pyruvate carboxylase PEP carboxykinase F1,6BP Glucose 6 phosphatase |
|
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(-) homogenistic oxidase
|
alkaptouria
(blk urine, joints) |
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(-) tyrosinase
|
albinism
|
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(-) tyrosine transport
|
albinism
|
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(-) cystathione beta synthase
|
homocystinuria
|
|
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(-) mmCoA mutase
|
metabolic acidosis
developmental delay |
|
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(-) histidase
|
+/- MR
histidemia |
|
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(-) renal tubular amino acid transporter
|
cystinuria
cystine stones |
|
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NADPH
|
product of HMP shunt
used in synthesis reactions respiratory burst P450 |
|
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arsenic
|
inhibits glyceradehyde-3-P
complexes with lipoic acid decreases ATP |
|
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(-) renal tubular amino acid transporter
|
cystinuria
cystine stones |
|
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|
(-) alpha ketoacid dehydrogenase
|
maple syrup urine disease
|
|
|
|
(-) adenosine demainase
|
SCID
|
|
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|
(-) HGPRT
|
Lesch Nyhan
|
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|
|
(-) orotic acid PRT or
5' P decarboxylase |
orotic aciduria
|
|
|
|
Glucose 6 PD deficiency
-genetic problem -pathophys -symptoms -histo |
Xr point mutation
low NADPH high ROS chronic hemolytic anemia +Heinz bodies +bite cells malaria R in blacks |
|
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|
Fructose intolerance
|
aldose B deficiency
autosomal recessive F1P accumulation, decreases available P inhibits glucogenolysisi, gluconeogenesis presents when baby weaned to outside food hypoglycemia, jaundice, cirrhosis, vomiting |
|
|
|
Essential fructosuria
|
(-) fructokinase
autosomal recessive benign fructosemia/uria |
|
|
|
Pyruvate dehydrongenase deficiency
|
XD or B1 deficiency
congenital lactic acidosis pyruvate shunted to lactate episodic atxia w/ carb rich meals, psychosis, MR, death Rx ketogenic diet |
|
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|
HMP shunt
|
produced NADPH for FFA and steroid biosynthesis
no ATP produced lactating mammary glands, liver, adrenal cortex, RBC G6PDH RLS Transketolases require B1 |
|
|
|
Classic galactosemia
|
(-) galactose 1-P UDT
autosomal recessive accumulation of galactitol in lens, liver, kidney b/c glucose 1-P can't be produced failure to thrive, jaundice, hepatomegaly, cataracts, MR |
|
|
|
Galatokinase deficiency
|
(-) galactokinase
autosomal recessive milder than classic galactosemia galactitol accumulates in lense, b/c galactose-1-P can't be produced infantile cataracts |
|
|
|
Lactase deficiency
|
lactose intolerance
bloating, cramps, osomotic diarrhea no mucosal change |
|
|
|
Glucogenic AA
|
VHAM (virginia baked ham)
Val His Arg Met |
|
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|
Glucogenic/ketogenic
|
PITT
Phe Ile Thr Trp |
|
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Ketogenic
|
Leu
Lys |
|
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Acidic
|
Asp , Glu (-)
|
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Basic
|
Arg, Lys, His
Arg Lys are in histones bind DNA |
|
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(-) glucose 6 P
|
Von Gierke/ GSDIa
|
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|
(-) translocase
|
GSD IIa
|
|
|
|
(-) acid maltase/lysosomal glucosidase
|
Pompe's
GSD III |
|
|
|
Ornithine transcarbamolyase deficienct
|
X-linked recessive
failure to synthesize urea poor ammonia elimination carbamoyl P--> orotic acid orotic acidemia/uria , hyperammonemia |
|
|
|
Phenylalanine products
|
tyrosine-->
dopamine, melanin, NE, Epi dopamine--> NE requires asorbic acid |
|
|
|
(-) GSD debranching enzyme
|
Cori's
GSD III |
|
|
|
(-) skeletal muscule glycogen phosphorylase
|
McArdle's
GSD IV |
|
|
|
Tryptophan products
|
niacin
serotonin--> melatonin req BH4 |
|
|
|
Histidine products
|
histamine
|
|
|
|
Glycine products
|
porphyrin--> heme
|
|
|
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Arginine products
|
creatinine
urea NO |
|
|
|
Glutamate products
|
GABA
Glutathione |
|
|
|
Phenylketouria
|
autosomal r
(-) phenylalaine hydroxylase or THB4 factor (-) tyrosine, melanin; tyr essential high phenylalanine--> excess phenylketones in urine dx 48 hrs after first meal MR growth retardation fair skin musty body odor eczema Maternal PKU-- poor dietary control--> microcephaly, congenital HD, growth retardation |
|
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|
Alkaptourina
|
autosomal r
(-) homogentistic acid oxidase tyrosine degradation pathway asymptomatic until 40yo dark CT, pigmented sclera urine oxidized black arthraglia, arthritis Rx low protein diet |
|
|
|
methionine product
|
homogenestic acid
|
|
|
|
alanine role
|
NH3 transport from muscule
|
|
|
|
glutamine role
|
NH3 transport--> purine, pyrmd.
|
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|
|
Homocystiuria
|
autosomal recessive
cystine becomes essential homocystiuria ectopic lens, skeletal abn, MR, osteoporosis, premature MI, stroke, CVD 1. cystathionine synthase deficiency -Rx low Met, hi Cys, B12, folate diet 2. dec affinity for CS for pyridoxal phosphate Rx. very high B6 diet 3. homoctysteine methyl transferase deficiency |
|
|
|
Cystinuria
|
autosomal recessive
defective renal AA tubular transporter in PCT -cys, ornithine, lys, arg cystinuria--> staghorn calculi Rx acetazolamide alkalinizes urine |
|
|
|
Maple syrup urine disease
|
(-) alpha-ketoacid dehydrogenase
blocked degradation of branched AA I Love Vermont Ile, Leu, Val high alpha-ketoacids in blood CNS defects, MR, death poor feeding, vomiting, metabolic acidosis Rx thiamine/B1 ; avoid L,I,Val |
|
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Orotic aciduria
|
autosomal r
inability to convert orotic acid UMP de novo pyrm ptwy MEGALOBLASTIC ANEMIA NO HYPERAMMONEMIA like OTC deficency |
|
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Von Gierke's / GSD Ia
|
(-) glucose-6-phosphatase
severe fasting hypoglycemia lactic acidosis glycogen deposits in liver can't be released no gluconeogenesis/glycogenolysis "camp k" Rx cornstarch, nocturnal glucose |
|
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Pompe's disease/ GSD II
|
(-) lysosomal glucosidase
normal blood glucose massive cardiomegaly HF death large cystolic glycogen vaculoses in heart, liver, muscle |
|
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|
GSD Ib
|
(-) translocase
g1,6,P to glucose 6-P (to glucose) severe hypoglycemia |
|
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Cori's disease/ GSD III
|
(-) debranching enzyme
milder type Ia moderate hypoglycemia normal lactate levels gluconeogenesis intact high glycogen, dextran stores |
|
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McArdle's disease/GSD V
|
(-) skeletal m. glycogen phosphorlyase
inability to breakdown glycogen stores weakness, painful cramps, myoglobinuria with exercise normal lactase and liver enzymes |
|
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|
Fabry's
-inheritance -deficiency -accumulation -sx |
X-linked recessive
(-)alpha galactosidase A ++globsides/ceramide trihexoside in macrophage and endothelial lysosomes burning, peripheral neuropathy of hands/feet angiokeratomas cv, renal disease |
|
|
|
Gaucher's
-inheritance -deficiency -accumulation -sx |
autosomal recessive
(-) beta glucocerebrosidase ++glucocerebroside hepatosplenomegaly, aseptic necrosis of femur, bone crises Gaucher cells macrophages that look like crumpled tissue paper ashkenazi Jews> Rx BMT |
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Niemann Pick disease
-inheritance -deficiency -accumulation -sx |
autosomal recessive
(-) sphingomyelinase ++sphingomyelin progressive neurodegeneration HSM cherry red macula foam cells |
|
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|
Tay Sach's disease
-inheritance -deficiency -accumulation -sx |
ar
(-) hexosaminidase A ++ GM2 ganglioside shell-like inclusions onion skin lysosomes progressive neurodegeneration rapid developmental delay cherry-red macula blindness, seizure |
|
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|
Krabbe's disease
-inheritance -deficiency -accumulation |
ar
(-) galactocerebrosidase ++galactocerebroside peripheral neuropathy developmental delay blindness, deafness optic atrophy, globoid cells near total demyleniation |
|
|
|
Metachromatic leukodystrophy
-inheritance -deficiency -accumulation |
ar
(-) arylsulfatase A ++ cerebroside sulfates central/peri demyleination ataxia, dementia, progressive paralysis nerves are yellow on cresyl violet |
|
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|
Hurler's syndrome
(MPS IH) -inheritance -deficiency -accumulation |
ar
(-) alpha L-iduronidase ++ heparan and dermatan sulfate devel. delay gargolyism, airway obstruction, corneal clouding cardiac ischemia-->death Rx BMT |
|
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Hunter's syndrome
-inheritance -deficiency -accumulation |
X LINKED RECESSIVE
(-) iduronate sulfatase ++heparan sulfate, dermatan sulfate mild Hurler's + aggressive behavior no corneal clouding "hunter's see clearly" and aim for the X (linked) mild MR/ deformities |
|
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Askenazi Jews>
|
Gaucher's
Niemann-Pick Tay-Sachs |
|
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Farber's
|
(-) ceramidase
(+) ceramide painful joint deformities SQ nodules hoarse cry granulomas |
|
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GM1 gangliodosis
|
(-) beta galactosidase
++ NANA , GM1, keratan sulfate neurodegeneration, cherry macula, HSM, skeletal defects |
|
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|
Refsum disease
|
auto r
(-) alpha-hydrolase +++branched FA xCNS |
|
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|
MCAD
Medium chain fatty acyl coA dehydrogenase deficiency |
ar
(-) FFA oxidation, gluocse, ketones severe hypoglycemia infants--> SIDS Rx rich carb diet |
|
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|
Carnitine deficiency
|
primary
(-)CPT1 -inability to utilized LCFA (--> glucose) -severe fasting hypoglycemia coma, detah (-) CPT2 cardiomyopathy, weakness, myoglobinemia w/ exercise Rx. low LCFA diet, carnitine supplements |
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|
100 m sprint energy supply
|
stored ATP
creatinine phosphase aneaerobic glycolysis |
|
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|
1000m run (minutes)
|
stored ATP
creatinine phosphase oxidative phosphorylation aneaerobic glycolysis |
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Fasting
Day 1-3 |
1) hepatic glycogenolysisis, glucose release
2) adipose release FFA 3) mucule and liver shift from glucose to FFA consumption (hours) 4) hepatic gluconeogensis from peripheral lactate, alanine, adipose glycerol, propionyl-CoA from odd-chain FFA |
|
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Fasting
> day 3 |
muscle protein converted to
ketone bodies for brain and heart consumption fat stores |
|
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|
Fasting
several weeks |
ketones main source of fuel as fat stores dwindle
loss of protein--> organ failure, death |
|
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Cholesterol synthesis
|
HMG reductase converts HMG CoA to mevalonate
cholesterol esterified by lecitchin cholesterol acyltransferase LCAT |
|
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|
HDL
|
synthesized in liver, intestines
delivers cholesterol from intestine to liver cholesterol>> |
|
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LDL
|
delivers liver cholesterol to periphery
synthesized from VLDL by lipoprotein lipase and hepatic TG lipase highest % cholesterol |
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|
VLDL
|
synthesized de novo in liver
TAG> deliveres de novo TAG to periphery --> IDL-->LDL |
|
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Chylomicron
|
delivers dietary fat,TG, cholesterol to periphery AND liver
TAG>>> |
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apoAI
|
activates LCAT
cholesterol esterification to HDL |
|
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apoB100
|
binds LDL receptor
mediates VLDL secretion from liver |
|
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apoCII
|
cofactor for lipoprotein lipase
|
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apoB48
|
chylomicron secretion
|
|
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apoE
|
liver remnant uptake
|
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|
cholesterol ester transfer protein
|
CETP mediates transfer of cholesterol esters to other lipoprotein particles
|
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|
hepatic TG lipase
|
degrades TG in IDL--> LDL
|
|
|
|
lipoprotein lipase
|
degrades TG in chylomicrons--> remnant
TG in VLDL--> IDL |
|
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|
hormone sensitive lipase
|
degrades TG in adiopocytes
|
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|
pancreatic lipase
|
degrades dietary TG in small intestine
|
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chylomicron apolipoprotein
|
"BACE"
B48 A-IV C-II E CHYLOMICRON = BACE |
|
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VLDL apolipoproteins
|
B100
CII E VLDL= BECII |
|
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IDL apolipoprotein
|
B100, E
IDL = BE |
|
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LDL apoprotein
|
B100
|
|
|
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HDL
|
C, E repository
|
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|
Familial hyperchylomicronemia
Type I |
elevated fasting serum chylomicrons
elevated TG, cholesterol (-) lipoprotein lipase or (-) apoCII no risk of CAD Rx low fat diet |
|
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|
Familial hypercholesterolemia
IIa |
↑LDL
↑ total cholesterol ↓LDL receptors CAD |
|
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|
Familial mixed hyperlipidemia
IIb |
↑LDL, VLDL, TG, cholesterol
Liver VLDL overproduction |
|
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Familial dysbetalipoproteinemia
III |
(-)/mutant apoE
↑IDL , TG, cholesterol xanthomas, CAD, PVD by middle age |
|
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|
Familial hypertriglyceridemia
IV |
VLDL hepatic overproduction
or ↓ lipoprotein lipase activity ↑VLDL ↓ or nl LDL ↑ or nl cholesterol ischemic HD |
|
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|
Familial mixed hypertriglyceridemia
V |
↑VLDL production or ↓ LPL activity
↑VLDL, chylomicrons , cholesterol, TG ↓ or nl LDL |
|
|
|
CAD risk of familial dyslipidemias
|
II > III, IV> I> V
Hypercholestrolemia mixed hyperlipidemia dysbetalipoproteinemia hypertriglyceridemia |
|
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Abetalipoproteinemia
|
autosomal recessive
(-) B100, B48 inability to synthesize lipoproteins failure to thrive, steatorrhea, acanthocytosis ataxia, night blindness TG accumulates in liver, intestines no chylomicrons formed |
|
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|
calculated LDL
|
LDL = cholesterol -HDL -TG/5
|
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|
Purine synthesis
|
orotic acid
PRPP + glycine, aspartate, glutamate, THF IMP yields AMP, GMP |
|
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|
Pyrmidine synthesis
|
Carbamoyl phosphate + aspartate
orotic acid PRPP UMP UDP + ribonucelotide reductase dUDP, CTP dUDP + thymidine synthase dTMP |
|
|
|
6 mercaptopurine MOA
|
inhibits purine (A,G) synthesis
|
|
|
|
hydroxyurea MOA
|
inhibits ribonucleotide reductase
(pyrimidine synthesis) UDP is not reduced to dUMP, CTP thymine not produced from dUMP |
|
|
|
5-flurouracil MOA
|
inhibits thymidylate synthase
inhibits thymidine (dTMP) production |
|
|
|
Methotrexate MOA
Trimethoprim MOA |
1) inhibits DHF
2) inhibits bacterial DHF dihydrofolate reducase prevents DHF reduction to THF backing up thymidine synthesis |
|
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|
DNA polymerase I
DNA polymerase III eurkaryotic or prokaryotic? |
both prokaryotic ONLY
|
|
|
|
xeroderma pigmentosum
-defect -sx |
auto r
poor nucelotide excision repair prevents thymidine dimer repair -dry skin,gross degradation -melanoma,SCC |
|
|
|
mismatch repair disorder
|
HPCC
-hereditary polypoid colorectal cancer |
|
|
|
immobile cilia
defect dyeninarm infertility bronchiectasis, recurrent sinusitis situs invertus |
Karagener's syndrome
|
|
|
|
-7q
elastin elfin facies MR verboise, very friendly, cheerful |
William's syndrome
|
|
|
|
Causes of B3 deficiency
|
Hartnup (low trp absoption)
Carcinoid (high trp metabolism) low B6 (isonaizid) |
|
|
|
adrenal insufficiency
|
B5 deficiency
|
|
|
|
causes of B6 deficiency
|
oral contraceptives
Isonaizid |
|
|
|
irritability
peripheral neuropathy seiures |
B6 deficiency
|
|
|
|
loss of vibration, propioception
spasticity dementia paresthesia abnormal myelin ACoA replacecs mmCOA oval macrocytes |
B12 deficiency
|
|
|
|
Diphyllobotrium lata
absence of terminal ileum Crohns |
B12 deficiency
|
|
|
|
high homocysteine
high methylmalonylic acid hypersegmented PMN |
B12 deficiency
|
|
|
|
phenytoin
MTX sulfonamides can cause... |
Folate deficiency
|
|
|
|
dermatitis
alocepia enteritis |
Biotin deficiency
B5 deficiency (+ adrenal insuff) |
|
|
|
iron reduction
dopamine --> NE |
vitamin C
|
|
|
|
collagen hydroxylation
|
vitamin C
|
|
|
|
excess vitamin D
|
sarcoidosis
|
|
|
|
protects RBC oxidant damage
|
vitamin E
|
|
|
|
hemolytic anemia with deficiency
|
vitamin E
E= erythrocytes |
|
|
|
hypogonadism
poor wound healing loss of adult pubic/axillary hair |
zinc deficiency
|
|
|
|
responsible for methionine, production
responsible for homocysteine production |
B12
S-adenyl-methoionin (ATP+methioine) |
|
|
|
carboxylation co-factor
|
biotin
|
|
|
|
cofactor for dopamine B-hydroxylase
|
vitamin C
|
|
|
|
HMP shunt products
|
ribulose-5-phosphate
NADPH for oxidative phosphorlation |
|
|
|
CO2 carrier
|
Biotin
|
|
|
|
CH3 carrier
|
S-adensyl-methionine (SAM)
|
|
|
|
C carrier
|
THF
|
|
|
|
aldehyde carrier
|
B1/ TPP
|
|
|
|
NAPDH uses
|
anabolic processes
respiratory burst CYP 450 |
|
|
|
liver glucokinase
tissue glucokinase |
glucokinase
-low affinity -transcption induced by insulin hexokinase -high affinity/ low K -glucose-P feedback inhibition sequesters glucose in liver by P after meal. |
|
|
|
arsenic MOA
|
inhibits glyceraldehyde-3
complexes with lipolic acid ATP levels reduced |
|
|
|
Regulation of Fed/Fasting state
|
F, 2, 6, BP
|
|
|
|
TCA cycle products
|
3 NADH
1 FADH2 2 CO2 1 GTP/ACoA 12 ATP/ aCOA x 2 = per glucose |
|
|
|
episodic ataxia with carb rich meal
lactic acidosis |
pyruvate dehydrogenase deficiency
<-- B1 deficiency congenital lactic acidosis |
|
|
|
pyruvate carboxylase function
|
pyruvate --> oxalacetate
(mitochondria) |
|
|
|
PEP carbokinase
|
oxaloacetate -> PEP
|
|
|
|
Glucogenesis
|
pathway produces fresh glucose
pyruvate carboxylase (mt) PEP carboxinase (cytosol) F1,6 bisphosphatase (cytosol) Glucose 6 phosphatase (ER) (-) of these enzymes cause hypoglycemia |
|
|
|
oligomycin MOA
|
inhibits ATPase
increases proton gradient |
|
|
|
cyanide
rotenone antimycin A MOA |
inhibits cytochromes
decreases proton gradient |
|
|
|
2,4, dinitrophenol
aspirin thermogenin |
uncoupling protein
H+ dissipation increased 02 consumption ATP not produced |
|
|
|
Urea cycle order and RLS
|
Ordinarily Carless Crappers Are Also Frivolous About Urination
Orinithine Carbamoyl phosphate synthase I (RLS) Citruline Asparate Argininosuccinate Fumarate Arginine Urea |
|
|
|
tyrosine --> thyroxine
Tryptophan--> Serotonin cofactor |
Biotin
|
|
|
|
Heme produced from______
|
glycine
|
|
|
|
Creatinine
Urea NO produced from |
Arginine
|
|
|
|
tyrosine
dopamine produced from__________ |
phenylalanine
|
|
|
|
cystathinone synthase defiency
Dx Rx |
homocystenuria
restrict Met Increase B12, cysteine |
|
|
|
Decreased affinity of cystathione synthase for B6
Dx Rx |
Homocystenuria
high vitamin B6 in diet |
|
|
|
Homocysteine methyltransferase deficiency
Dx |
Homocystenuria
|
|
|
|
tall
lens subluxation osteoporosis CAD, MI kyphosis MR |
homocysteinuria
|
|
|
|
poor feeding
metabolic acidosis mental retardation death increased alpha ketoacids |
Maple Syrup Urine Disease
(-) alpha ketoacid dehydrogenase Valine Isoleucine leucine |
|
|
|
no adenosine dehydrogenase
excess adenosine, dATP lymphopenia recurrent lifethreatening infections |
SCID
excess A inhibits ribonucleoside reductase and DNA synthesis no lymphocytes |
|
|
|
excess guanine, hypoxanthine, PRPP
low IMP, GMP retardation aggression gout, stones chorea |
Lesh-Nyahan
Xr |
|
|
|
megaloblastic anemia
orotic acidemia |
Ortoic acidemia
|
|
|
|
Insulin ___phosphorylates
___ cAMP/PKA |
dephosphorylates, decreases
|
|
|
|
Glucagon ___phosphorylates
___ cAMP/PKA |
increases cAMP/PKA
|
|
|
|
degradation of TG in IDL
|
hepatic triglyceride lipase
|
|
|
|
degradation of chylomicron and VLDL triglycerides
|
liprotein lipase
|
|
|
|
degrdation of dietary triglycerides in small intestine
|
pancreatic lipase
|
|
|
|
AI
|
binds LCADT
|
|
|
|
B100
|
binds LDL
mediates VLDL secretion |
|
|
|
CII
|
lipoprotein lipase cofactor
|
|
|
|
B48
|
mediates chylomicron secretion
|
|
|
|
aoplipoprotein E
|
remnant uptake by liver
|
|
|
|
synthesized in liver, intestines
cholesterol>> delivers cholesterol to liver f |
HDL
|
|
|
|
synthesized from VLDL by lipoprotein and hepatic TG lipase
HIGHEST % CHOLESTEROL delivers cholesterol from liver to periphery |
LDL
|
|
|
|
synthesized in liver
TG> delivers de novo TG to periphery degraded into IDL, LDL in blood |
VLDL
|
|
|
|
highest % triglycerides
transports dietary TG to liver, periphery |
chylomicron
|
|
|
|
ataxia
acantholysis failure to thrive steatorrhea no chylomicrons, high cholesterol, high TG thorny RBC hemolytic anemia 2/2 low vit E |
abetalipoproteinemia
|
|
