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187 Cards in this Set
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- Back
What is the composition of histone octamer?
Where does H1 histone protein belong? |
2 sets of H2A, H2B, H3, and H4. Positively charged (lysine and arginine). DNA wraps around histone octamer to form nucleosome.
H1 is not part of the octamer; it binds nucleosome octomers in a string. |
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Euchromatin vs heterochromatin
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Heterochromatin: transcriptionally inactive ("Highly Condensed)
Euchromatin: transcriptionally active (less condensed) |
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Acetylation vs hypermethylation of histone.
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acetylation: weakens DNA-Histone bond --> more transcription
hypermethylation: prevent transcription |
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Required components for:
1. Purine 2. Pyridmidine |
1. Purine: glycine, aspartate, glutamate ("GAG")
2. pyrimidine: Carbamoyl phosphate and Aspartate |
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Carbamoyl phosphate
What 2 metabolic pathways is this involved in? |
Urea cycle
De novo pyrimidine synthesis |
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Increased orotic acid, Megaloblastic anemia (does not improve with vit B12 or folate).
disease? inheritance pattern? |
Orotic aciduria: defect in either ortic acid phosphoribosyl transferase or orotidine 5-phosphate decarboxylase
Autosomal recessive |
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Orotic acid + hyperammonemia.
Disease? inheritance pattern? |
OTC (ornithin transcarbamoylase) deficiency
X-linked recessive |
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Hydroxyurea
MOA? indication? |
inhibits ribonucleotide reductase --> inhibits de novo pyrimidine synthesis
for sickle cell anemia (increase HbF) |
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Methotrexate and Trimethprime
MOA? difference? |
inhibits dihydrofolate reductase
MTX: eukaryotic cells TMP: prokaryotic cells |
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Adenosine deaminase deficiency
defective pathway? pathogenesis? associated disorder? |
Purine salvage pathway
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase -> prevents DNA synthesis and thus lower lymphocyte count. One of the major causes of SCID (severe combined immunodefieciency disease) |
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Lesch-Nyhan syndrome
defect? inheritance pattern? sxs? |
deficiency in HGPRT (used in purine salvage pathway) --> increased uric acid
X-linked recessive retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis |
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DNA topoisomerase
fxn? what antimicrobial blocks this enzyme? |
uncoils DNA
flouroquinolone |
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DNA polymerase I vs DNA polymerase III
|
DNA pol I: 5 --> 3 DNA exonuclease activity; degrades RNA primers
DNA pol III: 3 --> 5 DNA exonuclease activity; elongates both leading and lagging strands both are only in prokaryotes |
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Xeroderma pigmentosum
defect? |
defective endonuclease that removed damaged base (or thymidine dimers in this case)
|
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Lynch syndrome
defect? |
HNPCC (hereditary nonpolyposis colorectal cancer)
defective mismatch repair gene |
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How does radiation damage DNA?
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breaks DNA double strands and forms O2 free radicals, which further damages it
|
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3 main types of RNA and feature of each
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RMT (Rampant, Massive, Tiny)
rRNA: most abundant mRNA: longest tRNA: smallest |
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What is added at the 3 end of mRNA post trascriptionally? its fxns?
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poly A tails
prevent degradation signal to exit nucleus |
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TATA or CAAT box
what is it? |
promoter region on DNA
|
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RNA polymerase I, II, III
fxn? |
I: rRNA
II: mRNA III: tRNA in order of products produced |
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alpha-amanitin
|
found in death cap mushrooms
inhibit RNA polymerase II causes liver failure |
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hnRNA
what is it? fxn? |
hetergenous nuclear RNA
mRNA before post-transcription |
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snRNP
what is it? fxn? related diseases? |
snRNPs and other proteins form spicesome, which splice out intron and spice in exons.
mixed connective disorder and lupus pts make antibodies aginst snRNPs. |
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Mischarged tRNA
defect? |
reads the usual codon but carries a wrong AA
|
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enzyme responsible for adding amino acid to tRNA?
where on tRNA? what is the common code at the site? |
aminoacy-tRNA synthase
AA added on the 3 end and has CCA code on it |
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3 sites of ribosome complex and their fxns?
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A site: incoming Aminoacyl tRNA
P site: accomodates growing Peptide E site: holds Empty tRNA as it exits |
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energy requirement for translation of each amino acid.
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tRNA aminoacylation: ATP --> AMP (charging tRNA)
Loading tRNA onto ribosome: GTP --> GDP translocation: GTP --> GDP total 4 high energy Pi |
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ubiquitin
what is it? fxn? |
attached to defective protein for degradation
|
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telomerase
what is it? fxn? |
reverse transcriptase that adds TTAGGG repeats to the 3 end of DNA
a RNA-dependent DNA polymerase |
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cyclin-CDK complex
fxn? |
both must be activated or inactivated for the cell cycle to progress
|
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Rb or P53
what are they? |
tumor suppressor genes
inhibits G1 to S progression |
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Permanent, stable or labile?
Lymphocyte |
stable (enters G1 from G0)
|
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Permanent, stable or labile?
RBC |
permanent (remains in G0)
|
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Nissl bodies
what are they? fxn? |
RER in neurons
produces peptide neurotransmitters |
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Give 2 examples of cells that are rich in RER.
rich in smooth ER? |
rich in RER: mucous-secreting goblet cells, plasma cells
rich in smooth ER: hepatocytes and adrenal cortical cells |
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I cell disease
defect? sxs? |
failure of addition of mannose-6-phsphate to lysosome protein
lysosomal proteins are secreted coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes |
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Clathrin protein
fxn? |
trafficking protein:
trans-golgi --> lysosomes plasma membrane --> endosomes (receptor-mediated endocytosis) |
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List 2 drugs that inhibit microtubule polymerization.
List 1 drug that hyperstabilize microtubule. |
inhibit polymerization: vincristine/vinblastine, colchicine
hyperstabilization; Paclitaxel/taxols |
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Chediak-Higashi syndrome
defect? sxs? |
microtubule polymerization defect --> decreased phagocytosis
recurrent pyogenic infections (staph, strep) partial albinism peripheral neuropathy |
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Cilia structure
what protein is incorporated? |
9+2 microtubule arrangement
dynein |
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Kartagener's syndrome
defect? sxs? |
immotile cilia due to a dynein arm defect
male/female infertility bronchietasis recurrent sinusitis situs inversus |
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What tissue is associated following IHC markers?
Vimetin Desmin |
Vimetin: connective tissue
Desmin: muscle |
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2 drugs that disrupt Na/K pump.
|
Ouabain
Cardiac glycosides (digoxin, and digitoxin): blocks Na/K --> increase Ca/Na antiport action --> increase intracellular Ca |
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List 4 types of collagen and associated tissues.
|
Be (So Totally) Cool, Read Books
Type I: bone, skin, tendon type II: cartilage type III: reticullin (skin, blood vessels, uterus, fetal tissue, granulation tissue) type IV: Basement membrnae |
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What disease(s) is associated following deficiency?
type I collagen type III collagen type IV collagen fibrillin |
type I collagen: Osteogenesis imperfecta
type III collagen: Ehlers-Danlos syndrome type IV collagen: Goodpasture's, Alport's fibrillin-1: Marfan's |
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What 3 AAs are most abundant in collagen chains?
What vitamin is needed for collagen synthesis? if deficient? |
Glycine-proline-lysine
Vitamin C; Scurvy if deficient |
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What enzyme cross-links tropocollagen to make collage fibrils? What does it link?
|
links lysine and hydroxylysine by lysyl oxidase
|
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What accounts for elastin's ability to recoil?
What enzyme is responsible for making this property? |
due to desmosine cross-linking b/t lysyl residues with elastin chains
lysyl hydroxylase cross-links the elastin |
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Ehlers-Danlos syndrome
defect? sxs? |
type III collagen deficiency
hyperextensible skin, easy bruising, hypermobile joint, berry aneurysm |
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Osteogenesis imperfecta
defect? sxs? genetic pattern? |
type I collagen deficiency
Multiple fractures with minimal trauma blue sclerae hearing loss dental imperfection autosomal dominant (most common) |
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Alport's syndrome
defect? sxs? genetic pattern? |
type IV collagen
deafness, nephritis X-linked recessive |
|
Microarrays
What is this used for? |
used to detect single nucleotide polymorphism or to profile gene expression levels
|
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RNAi
What is it? used for? |
dsRNA complementary to mRNA.
when transfected into human cells, dsRNA separates and promotes degradation of target mRNA, knocking down gene expression |
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Pleiotropy
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A single gene mutation results in multiple phenotype manifestations; PKU.
|
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Imprinting
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differences in phenotype depend on whether the mutation is maternal or paternal origin
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loss of heterozygosity
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If a pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops.
not true of oncogenes |
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Heteroplasmy
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presence of both normal and mutated mtDNA, resulting in variable expression of mitochondria inherited disease
|
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Hardy-Weinberg equation
how do you calculate prevalence of X-linked recessive diseases? |
p^2 +2pq + q^2 = 1 (equals disease prevalence)
p + q =1 (equals allele prevalence) in X-linked recessive disease q= disease prevalence in male q^2 = disease prevalence in female |
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Prader-Willi syndrome
defect? sxs? |
deletion of normally active Paternal allele on chrom 15
MR, hyperphagia, obesity, hypogonadism, hypotonia |
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Angelman's syndrome
defect? sxs? |
deletion of normally active maternal allele on chrom 15
MR, seizures, ataxia, inappropriate laughter |
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List 3 examples of mitochondral inheritance pattern diseases.
|
Myoclonic epilepsy with ragged red fibers (MERRF)
Leber's hereditary optic neuropathy Mitochondrial encephalopathy with stroke-like episodes and lactic acidosis (MELAS) |
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Hypophosphatemic rickets
inhertiance pattern? presenation? |
x-linked dominant
rickets-like presentation due to increased PO4 wasting |
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What inheritance pattern is associated with the following:
defective structural genes enzyme deficiencies |
defective structural genes: autosomal dominant
enzyme deficiencies: autosomal recessive |
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Marfan's syndrome
defect? sxs? complications? |
fibrillin gene mutation
tall with long extremities, pectus excavatum, hyperextensive joints, and long, tapering fingers/toes (arachnodactyly) dissecting aneurysm (due to cystic medial necrosis of aorta) floppy mitral valve subluxation of lenses |
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Neurofibromatosis 2
genetic defect? associated diseases? |
NF2 gene mutation on chrom 22
bilateral Schwanomma, juvenile cataracts |
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Cystic fibrosis
genetic defect? cellular changes in the lung and sweat glands? how you so dx? |
AR, CFTR gene defect on chrom 7 (deletion of Phe) --> defective chlorine channels
Lungs (epithelial tissues): decreased Cl secretion --> increased Na/H20 reabsorption --> dry Sweat glands: decreased Cl- reabsorption and Na reabsorption dx via sweat test |
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Pseudohypertrophy of calf muscles, Gower's maneuever
dx? defective gene? inheritance? |
Duchenne's muscular dystrophy
deletion of dystrophin gene X-linked recessive |
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List X-linked recessive disorders.
|
Be Wise, Fool's GOLD Heeds Hope
Bruton's agammaglobulinemia Wiskott-Aldrich Fabry's disease G6PD deficiency Ocular albinism, ornithine transcarbamolyase deficiency Lesch-Nyhan syndrome Duchenne's (Becker's) Hunter's Syndrome Hemophilia A and B also, Alport's syndrome |
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Fragile X syndrome
defective gene? genetic findings? findings? |
defective FMR1 gene
CGG trinucleotide repeat disorder 2nd most common cause of MR (after Down's) macro-orchidim, long face with a large jaw, large everted ears, autism, mitral valve prolpase |
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List 4 trinucleotide repeat expansion diseases.
What genetic feature do they all share? |
Try hunting for my friend eggs (X)
Huntington's (CAG) myoTonic dystrophy (CTG) Fragile X syndome (CGG) Freidreich ataxia (GAA) genetic anticipation |
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Down's syndome
genetic defects? causes of genetic defects (3)? findings? |
trisomy 21 due to meiotoic nondisjuction (95%), robertosonian translocation (4%), Down mosaicism (1%)
MR (most common cause), epicanthal folds, simian crease, duodenal atresia, congenital heart disease (most commonly septum primum ASD) Decreased AFP, estriol and increased beta-hCG and inhibin A in amniocentesis |
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Edward's
genetic defect? findings? |
trisomy 18
severe MR, rocker-bottom feet, micrognathia, clenched hands usually die within 1 year of birth |
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Patau's
genetic defect? findings? |
trisomy 13
severe MR, rocker-bottom feet, cleft lip/palate, holoProsecephaly, Polydactyly usually die within 1 yr of birth |
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Robertsonian translocation
what is it? affected chromosomes? |
occurs when the long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost
13, 14, 15, 21, and 22 |
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Cri-cu-chat syndrome
genetic defects? findings? |
congenital microdeletion of 5p (p=short arm)
microcephaly, MR, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities |
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Williams syndrome
genetic defects? findings? |
congenital microdeletion of 7q (q=long arm)
"elfin" facies, MR, hypercalcemia, well-developed verbal skills, extreme freindliness with strangers, cardiovascular problems |
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2 syndromes associated with 22q11 deletion?
defects for each? |
DiGeorge syndrome: thymic, parathyroid, and cardiac defects (truncus arteroisus, tet of Fallots)
Velocardiofacial syndrome: palate, facial, cardiac defects |
|
List water soluble vitamins.
Which ones stay in the system for a while? (2) |
B1 (Thiamine: TPP)
B2 (riboflavin: FAD, FMN) B3 (niacin: NAD+) B5 (panthothenic acid: CoA) B6 (pyridoxine: PLP) B7 (biotin) B12 (cobalamin) C (ascorbic acid) folate B12 and folate stay in the system b/c they are stored in the liver |
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List common sxs of vitamin B complex deficiency.
|
dermatitis, glossitis, and diarrhea
|
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Isoretinoin
indication? requirement before using it? why? |
indicated for acne
pregnancy test before using it b/c it is a form of Vit A, which is teratogenic |
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TPP
what vitamin? cofactor what enzymes? (4) |
B1 (thiamine)
Pyruvate dehydrogenase (glycolysis) alpha-ketoglutarate (TCA cycle) Transketolase (HMP shunt) branched-chain AA dehydrogenase |
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Wernicke-Korsakoff syndrome
what causes it? sxs? irreversible sxs? |
due to thiamine (B1) deficiency; usually associated with chronic alcoholism and malnutrition
Wernicke: confusion, opthalmoplegia, ataxia Korsakoff: memory loss, confabulation, personality change Korsakoff sxs are irreversible b/c the damage to medial dorsal nucleus of thalamus is permanent |
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Niacin
what vitamin? what AA is it made from? cofactor for what type of reaction? |
vitamin B3
made from tryptophan (requires B6) constituent of NAD+, NADP+, which are used in redox rxns |
|
vitamin B3 deficiency
List 3 causes. sxs? |
1. Hartup disease (decreased tryptophan reabsorption in the proximal tubule)
2. carcinoid syndrome (increased tryptophan metabolism; used as serotonin) 3. INH (decrease vit B6, which is required to make B3) sxs: Pellagra (diarrhea, dementia, dermatitis) and glossitis |
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Pyridoxine
what vitamin? fxns? (7) Deficiency sxs? |
vitamin B6
used as a cofactor for: 1. transmination (GABA Transaminase, ALT, AST) 2. decarboxylation (Glutamate Decarboxylase, DOPA Decarboxylase) 3. glycogen phosphorylase 4. cystathione synthesis 5. heme synthesis (ALA Synthase) 6. synthesis of niacin from tryptophan 7. synthesis of histamine from histidine sxs: Convulsions, Hyperirritability, sideroblastic anemia, peripheral neuropathy. |
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Drugs that decrease pyridoxine (2)
|
INH
oral contraceptives |
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Which one has a larger reserve pool: cobalamin or folate?
clinical significance of having a small or large reserve pool? |
cobalamin: very large reserve pool in the liver
folate: small reserve pool in the liver; most common vitamin deficiency in US (remember, small reserve pool) |
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What parasite can cause vitamin B12 deficiency?
What are 2 elevated serum markers for B12 deficiency? |
Diphyllobothrium latum --> Vit B12 deficiency
Elevated homocysteine, and methymalonylic acid |
|
increased anion gap acidosis, hypoglycemia, ketosis, increased methymalonylic acid.
suspect? |
Methylmalnonylic acidemia due to deficiency in Methylmalonyl Coa Mutase
Isomerase: methylmalonyl-Coa --> succinyl-CoA |
|
S-adenosyl-methinoine (SAM)
fxn? regeneration of SAM requires? |
SAM transfers methylunit; required for NE --> E and methionine to homocysteine
regeneration requires Vit B12 and folate |
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What general reaction uses biotin as a cofactor?
What 3 pathways utilize biotin? |
cofactor for carboxylation enzymes (add 1 carbon goup)
1. generation of oxaloacetate (for TCA or gluconeogenesis; pyruvate carboxylase) 2. synthesis of FA chain ( Acetyl Coa Carboxylase) 3. odd # FA beta oxidation |
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List 4 functions of ascorbic acid.
|
ascorbic acid = vitamin C
1. antioxidant 2. facilitate Fe absorption by keeping it at reduced state (Fe2+) 3. for hydroxylation of proline and lysine in collagen synthesis 4. for dopamine Beta-hydroxylase, which converts dopamine to NE |
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Vitamin K
Biochemical action? necessary for synthesis of what substances? |
catalyzes gamma-carboxylation of glutamine acid residues on various proteins concerned with blood clotting
coagulation factors II, VII, IX, X, proteins C and S |
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What is the pathogenesis of hepatocellular steatosis seen in chronic alcoholics?
|
ethanol metabolism --> increased NADH/NAD+ in liver
not enough NAD+ to drive TCA cycle and beta oxidation -> TG accumulation |
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Kwashiorkor
cause? sxs? |
protein malnutrtion
MEAL Malnutrition (protien) Edema (swollen belly) Anemia Liver (fatty) due to decreased apolipoprotein synthesis |
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Marasmus
cause? sxs? |
overall energy malnutrtion
tissue and muscle wasting loss of subQ fat variable edema |
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List 3 metabolic pathways that take place in both mitochondria and cytoplasm
|
HUG
Heme synthesis Urea cycle Gluconeogenesis |
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Metabolism of one glucose molecule results in how many ATPs?
|
30 ATPs in muscle (via glycerol-3-phosphate shuttle)
32 ATPs in heart and liver (via malate-aspartate shuttle) |
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List 4 processes that utilize NADPH.
|
1. anabolic process
2. respiratory burst 3. P450 4. glutatione reductase |
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Hexokinase vs Glucokinase in terms of:
1. fxn 2. location 3. Km, Vmax 4. action of insulin |
1. both add Pi to glucose
2. Hexokinase is ubiquitous, glucokinase is in liver and beta cells of pancreas 3. Hexokinase: low Km, low Vmax Glucokinase: high Km, High Vmax 4. only glucokinase is induced by insulin |
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What is the fxn of:
1. Hexokinase 2. glucokinase |
Hexokinase: trap glucose in the tissue
glucokinase: to sequester excess glucose in the liver (glucose "buffer"); induced by insulin |
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List 5 cofactors for pyruvate dehydrogenase.
What 2 other enzyme complexes use the same set cofactors? |
1. pyrophosphate (B1, thiamine; TPP)
2. FAD (B2) 3. NAD (B3) 4. CoA (B5) 5. Lipoic acid alpha-ketoglutarate dehydrogenase complex alpha-ketoacid dehydrogenase |
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What is the rate-limiting enzyme for glycolysis?
list 2 inducers and 2 inhibitors |
Phosphofructokinase-1
Inducers: F-2,6-P, AMP Inhibitors: ATP, citrate |
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Describe how F-2,6-BP is regulated.
|
F-2,6-BP induces PFK-1, which is the rate-limiting enzyme for glycolysis.
Fed state: insulin -> high PFK-2 activity, low FBP-2 activity -> more F-2,6-P -> glycolysis fasting state: glucagon -> high FBpase-2 activity, low PFK-2 activity --> less F-2,6-P --> gluconeogenesis |
|
Pyruvate kinase deficiency
sxs? |
Pyruvate kinase is used for making pyruvate
hemolytic anemia due to inability to maintain Na/K pump |
|
What inhibits lipoic acid, presents with vomiting, rice water stools, garlic breath?
|
Arsenic poisoning
|
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Pyruvate dehydrogenase deficiency
what is increased in the serum? findings? tx? |
increased lactic acid
neurologic defects tx with high ketogenic nutrients (Lys, Leu, high fat diet) |
|
Cori cycle
fxn? energy cost? |
Transfers Lactate from muscle & RBC to the liver for gluconeogenesis. Glucose produced is moved back to the tissue for glycolysis.
costs 4 ATPs |
|
TCA cycle
how many ATPs are generated per cycle? list 3 irreversible enzymes |
3 NADH, 1 FADH, 1 GTP = 12 ATPs per cycle
citrate synthase alpha-ketoglutarate dehydrogenase Isocictrate dehydrogenase |
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How is the NADH made from glycolysis and krebs cycle transferred to electron transport chain?
|
glycerol-3p shuttle or malate-aspartate shuttle
|
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Oligomycin
what is it? what metabolic process is halted? |
mitochondrial ATPase inhibitor
halts oxidative phosphorylation; increased proton gradient but no ATP is produced |
|
CN-, CO poisoning
How do they affect oxidative phosphorylation? |
direct electron transport inhibitors
a decrease in proton gradient and block ATP synthesis |
|
2,4 DNP, Aspirin, Thermogenin
how does it affect oxidative phosphorylation? what endogenous substance has a similar property? |
uncoupling agent
increased permeability of membrane --> decreased proton gradient and increased O2 consumption. ATP synthesis stops but electron transport chain continues --> generates heat thermogenin in brown fat |
|
List 3 potential substrates for gluconeogenesis.
|
Propyl-CoA (from odd-chain FA)
Oxaloacetate Alanine |
|
List 4 Irreversible enzymes for gluconeogenesis.
|
Pathway Produces Fresh Glucose
Pyruvate carboxylase (biotin) PEP carboxylase Fructose-1,6-bisphosphatase Glucose-6-phosphatase |
|
What type of FA can enter gluconeogenesis? why
|
Odd-chain FA b/c it produces propyl-CoA, which can enter TCA and converted to oxaloacetate.
even-chain FA produces acetyl-CoA, which can't enter gluconeogenesis |
|
What is the purpose of HMP shunt
Energy cost? |
aka Pentose phosphate pathway
to generate NADPH for various reactions and F6P, G3P for glycolysis and ribose 5p zero ATP used |
|
List 2 main enzymes for HMP shunt?
Rate limiting step? cofactor used? |
Glucose-6-phosphate dehydrogenase (G6PD): rate-limiting
transketolase: requires B1 |
|
NADPH Oxidase deficiency
what disease? findings? |
chronic granulomatous disease
recurrent infection with catalase + organisms (Staph aureus, E coli, aspergeillus etc) |
|
G6PD defiency
findings? inheritance pattern? |
Intrinsic hemolytic anemia (normocytic), bite cells, Heinz bodies
due to inability to detoxify free radicals X-linked recessive |
|
Aldolase B deficiency
accumulated substance? sxs? milder form? |
Fructose-1-p
hypoglycemia, jaundice, cirrhosis, vomiting Milder form: defect in fructokinase; frutose in urine and blood |
|
Infantile cataracts, jaundice, hepatomegaly, Mental retardation
dx? defect? milder form? |
Galatosemia due to galactose-1p uridyl transferase defiency
galatokinase deficiency: milder form (presents with galactose in blood and urine and cataracts) |
|
sorbitol dehydrogenase deficiency
accumulated substance? affected tissues? unaffected tissues? affected group? |
Sorbitol accumulation (glucose -> sorbitol by aldose reductase)
affected tissues: kidney, peripheral nerves/schwann cells, retina, lens unaffected tissue: liver, ovaries, seminal vesicles common in chronic DM pts |
|
why are liver, ovaries, and seminal vesicles unaffected by sorbitol accumulation?
|
They have sorbitol dehydrogenase, which converts sorbitol to fructose
|
|
lactase deficiency
sxs? where is the enzyme located? |
lactase is a brush-border enzyme in the small intestine
bloating, cramps, osmotic diarrhea |
|
List 4 glucogenic amino acids.
|
MAV H
Met Arg Val His |
|
List 4 amino acids that are both glucogenic and ketogenic.
|
PITT
Phe Ile Thr Trp |
|
List 2 amino acids that are ketogenic
|
Lysine, Leucine
|
|
What 2 amino acids are needed for growth?
|
Arg and His
|
|
List 2 amino acids that are major components of histone.
|
Arg and Lys (+ molecules)
|
|
List 2 sources of nitrogen groups in urea cycle.
|
Ammonium (NH4+)
Aspartate |
|
NAG synthase defiency.
What metabolic pathway is affected? how? |
urea cycle
NAG (N Acetylglutamate) activates carbamoyl phosphate synthetase I, which is the rate-limiting enzyme for the urea cycle |
|
what 2 urea cycle enzymes are in the mitochondria?
|
Carbamoyl phosphate synthetase I
Ornithine transcarbamoylase |
|
What transports NH3 from peripheral tissue to liver for eventual metabolism and excretion?
|
alanine
|
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what amino acid acts as an NH3 carrier inside the cell?
|
glutamate
|
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Hyperammonemia
What metabolic pathway is inhibited as a result of increased NH4? why? |
TCA cycle is inhibited b/c excess NH4+ depletes alpha-ketoglutarate
|
|
2 drugs used to tx hyperammonemia.
|
Benzoate
Phenybutyrate both bind to AA and lead to excretion |
|
Increased orotic acid
list 2 ddx. |
defect in orotic acid -> UMP in de novo pyrimidine synthesis
ornithine transcarbamoylase deficiency (OTC) |
|
Ornithine transcarbamoylase deficiency (OTC)
inhibited metabolic process? findings? |
urea cycle is inhibited
increased orotic acid, hyperammonemia, decreased BUN |
|
4 amino acid derivatives that require B6 as a cofactor?
|
Niacin
Histamine Porphyrin --> heme GABA |
|
What AA is the precursor to following AA derivatives?
1. Heme 2. melatonin 3. GABA 4. NO |
1. Heme: glycine
2. melatonin: tryptophan 3. GABA: glutamate 4. NO: arginine |
|
What are the enzyme and cofactor used for the following synthesis?
1. Dopamine -> NE 2. NE -> epinephrine |
1. Dopamine -> NE: dopamine beta hydroxylase; requires vit C
2. NE -> epinephrine: PNMT, requires SAM |
|
Mental retardation, growth retardation, fair skin, eczema, musty body odor
dx? tx? |
Phenyketouria
decreased phenylalanine and increased tyrosine in the diet |
|
List 2 causes of phenylketouria.
|
decreased phenylalanine hydroxylase
decreased BH4 (a cofactor for Phe hydroxylase) |
|
Alkaptouria
deficiency? what pathway is affected? sxs? |
deficiency in homogentistic acid oxidase
degradative pathway of tyrosine Sxs: dark connective tissue, pigmented sclera, arthralgias, urine turns black. |
|
List 3 causes of albinism.
associated complication? |
1. tyrosinase deficiency
2. defective tyrosine transporter 3. lack of migration of neural crest cells associated with increased risk of skin cancer due to no melanin |
|
what special genetic feature does albinism have?
|
variable inheritance due to locus heterogeneity
|
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Congenital disease with MR, increased homocystine in urine, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis
dx? defects? Complications? |
Homocytinuria due to:
Cystathionine synthase deficiency decreased affinity cystathione synthase for B6 OR homocysteine methylase transferase deficiency complications: DVT, Stroke, Dislocation of lens, |
|
Cystic kidney stones (cystinuria)
common cause? tx? |
hereditary defect of renal tubular AA transporters for cysteine, ornithine, lysine, and arginine in the PCT
tx: acetazolamide to alkalinize the urine |
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Maple syrup disease
defect? findings? |
blocked degradation of branched AA (Ile, Leu, Val) due to decreased alpha-ketoacid dehydrogenase
Urine smells like maple syrup ("burned sugar" smell) severe CNS defects, MR and death |
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Hartnup disease
defect? findings? |
defective neutral AA transporter on renal and intestinal epithelial cells
pellagra (diarrhea, dementia, dermatitis) |
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What is the rate-limiting enzyme for glycogenolysis.
List inducers (3) and an inhibitor (1). |
Glycogen phophorylase
Inducers: Glucagon (liver), Epi (liver/muscle), Ca++/calmodulin (muscle); all phosphorylate the enzyme inhibitor: insulin (dephosphorylates the enzyme) |
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What is the first step of glycogenolysis? main product?
2nd step? |
1st step: glycogen phosphorylase to cleave 1,4 bonds until 4 glucose residues are left (limit dextran)
2nd step: debranching enzyme cleaves 1,6 bond |
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List 4 important glycogen storage diseases.
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Very Poor Carb Metabolism
Von Gierke's (type I) Pompe's disease (type II) Cori's disease (type III) McArdle's disease (type V) |
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What enzyme is alternatively used to cleaven glycogen to glucose molecules (minor pathway)?
associated disease if deficient? |
Lysosomal alpha1,4 glucosidase (acid maltase)
Pompe's disease (type II) |
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Von Gierke's disease
defect? findings? |
glucose-6-phosphatase deficiency
type I severe fasting hypoglycemia, increased glycogen in liver, high blood lactate, hepatomegaly |
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congenital, increased glycogen in liver, cardiomegaly
dx? defect? |
Pompe's disease
defective lysosomal alpha 1,4 glucosidase (acid maltase) |
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congenital, increased glycogen in muscle, painful muscle cramping and myoglobinuria with exercise
dx? defect? |
McArdle's disease (type V)
skeletal muscle glycogen phosphorylase deficiency |
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List X-linked recessive lysosomal storage disorders (2)
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Fabry's disease
Hunter's syndrome |
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List 3 lysosomal storage diseases common in Ashkenazi jews.
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Niemann-Pick
Tay-Sachs Gaucher's disease |
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Peripheral neuropathy of hands/feet, angiokeratomas, CV and renal disease
increased ceramide trihexoside in blood dx? defect? |
Fabry's disease
alpha-galactosidase A deficiency |
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Hepatosplenomegaly, aspectic necrosis of femur, bone crises, increases glucocerebroside.
dx? defect? hallmark cell? |
Gaucher's disease
defective Beta-glucocerebrosidase Gaucher's cells (macrophages that look like crumpled tissue paper) |
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Niemann-Pick disease vs Tay-Sachs disease
common findings? difference? defect and accumulated substance? |
common findings: progressive neurodegeneration, developmental delay, cherry-red spot on macula
difference: hepatosplenomegaly ONLY IN Niemann-Pick Niemann-Pick: deficiency in sphongomyelinase and accumulated sphingomyelin Tay-Sachs("SaX): deficiency in HeXosaminidase A and accumulated GM2 ganglioside |
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2 diseases with heparin sulfate, dermatan sulfate accumulation?
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Mucopolysaccharidoses
Hurler's syndrome Hunter's syndrome |
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Hurler's syndrome
defect? findings? accumulated substance? |
alpha-L-iduronidase deficiency
accmuluated heparan sulfate and dermatan sulfate developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly |
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What shuttle is used to transport FA for FA synthesis? Where is it transported to?
for beta-oxidation? |
FA synthesis: citrate shuttle; out of mitochondria to cytoplasm
Beta oxidation: Carnitine shuttle; out of cytoplasm into the mitochondria |
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Carnitine deficiency
What process is halted? findings? |
beta oxidation due to lack of carnitine shuttle, which transport FA into mitochondria
hypoketotic hypoglycemia weakness, hypotonia |
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Acyl-CoA dehydrogenase deficiency
findings? |
decreased ability to oxidize fatty acid
increased dicarboxylic acids hypoglycemia after fasting with decreased ketones |
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List 2 examples of ketone bodies.
How and where are they formed? where are they used primarily? |
acetoacetate and beta-hydroxybutyrate
in the liver, fatty acids and amino acids are metabolized to make ketones used in muscle and brain |
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List 3 states that causes high ketone levels.
Why do ketones form in each state? |
starvation: depletion of oxaloacetate
diabetic keoacidosis: depletion of oxaloacetate chronic alcoholism: NADH shunts oxaloacetate to malate all stall TCA cycle --> ketone generation |
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List 4 sources for hepatic gluconeogenesis when starving for 2 days.
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1. glycerol (as glycerol phosphate but has to be delivered to the liver b/c adipocytes cannot convert glycerol to glycerol-p)
2. lactate (via Cori cycle) 3. Amino acids (as oxaloacetate and a-ketoglutarate) 4. propionyl-CoA (from odd # FA) |
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Apolipoprotein A-I
associated lipoprotein? fxn? |
associated with HDL
activates LCAT, which esterifies the trapped cholesterol in the HDL |
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Apolipoprotein B-100
associated lipoproteins? fxn? |
VLDL, IDL, LDL
binds to LDL receptor, mediates VLDL secretion |
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Apolipoprotein E
associated lipoproteins? fxn? |
chylomicron, chylomicon remnant, VLDL, IDL
mediates Extra (remnant) uptake; delivers chylomicron remnant and IDL back to liver after distributing TGs in the peripheral tissue |
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Apolipoprotein CII
associated lipoproteins? fxn? what protein has the opposite fxn? |
chylomicron, chylomicron remnant, VLDL
increases lipoprotein lipase activity apo C-III has the opposite fxn |
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HDL
fxn and route? |
mediates reverse cholesterol transport form periphery to liver.
act as a repository for apoC and apoE, which are needed for chylomicron and VLDL metabolism secreted from both liver and intestine |
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LDL
fxn and route? |
delivers hepatic cholesterol to peripheral tissues.
formed by lipoprotein lipase modifacation of VLDL in the peripheral tissue taken up by target cells via receptor-mediated endocytosis |
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LCAT and CETP
fxn? |
LCAT: catalyzes esterification of cholesterol
CETP: mediates transfer of cholesterol esters to other lipoprotein particles (VLDL, LDL, IDL) |
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Increased chylomicron, TG, and choleterol?
what type of dyslipidemia? defect? |
hyperchylomicronemia (type I)
lipoprotein lipase deficiency or altered apolipoprotein C-II |
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Absent or LDL receptor
dx? findings? |
familial hypercholeterolemia (type IIa)
accelerated atherlsclerosis, tendon xanthomas, corneal arcus |
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type IV dyslipidemia
cause? findings? |
hepatic overproduction of VLDL
causes pancreatitis increased VLDL and TG |
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Abetalipoproteinemia
deficiencies? findings? |
inability to synthesize lipoproteins due to deficiencies in apoB-100 and apoB-48
failure to thrive, steatorrhea, acanthocytosis, ataxia, nightblidness, fat accumulation within enterocytes |
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HMG-CoA reductase inhibitors
3 side effects |
hepatotoxicity (increased LFTs)
rhabdomyolysis teratogenic |
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Niacin
MOA? 4 side effects? |
MOA:
inhibit lipolysis in adipose tissue reduces hepatic VLDL secretion into circulation side effects 1. red, flushed face, which is decreased by aspirin or long-term use 2. hyperglycemia (acanthosis nigricans) 3. hyperuricemia (exacerbates gout) 4. hepatotoxicity |
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2 lipid lowering agents that increase the risk of cholesterol gallstones
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bile acid resins (cholestyramine, colestipol, colesevelam)
Fibrates (gemfibrozil, clofibrate, bezafibrate, fenofibrate) |
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what lipid lowering agent is best at lowering TG?
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Fibrates (gemfibrozil, clofibrate, bezafibrate, fenofibrate)
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What lipid lowering agent is the doc to raise HDL?
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Niacin
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