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187 Cards in this Set
- Front
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What is the composition of histone octamer?
Where does H1 histone protein belong? |
4 pairs to form a nucleosome, which bind to negatively charged DNA
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: not accessible for transcription ("Highly Condensed)
Euchromatin: accesible for transcription |
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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
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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
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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
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
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Permanent, stable or labile?
RBC |
permanent
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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.
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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.
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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?
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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 |
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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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one gene, multiple phenotypes
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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
p + q =1 in X-linked recessive disease p = disease prevalence in male q^2 = disease prevalence in female |
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Prader-Willi syndrome
defect? sxs? |
delection 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.
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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.
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Be Wise, Fool's GOLD Heeds Silly 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
microcephaly, MR, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities |
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Williams syndrome
genetic defects? findings? |
congenital microdeletion of 7q
"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 |
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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.
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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 constituent of NAD+, NADP+, which are used in redox rxns |
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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? (6) |
vitamin B6
used as a cofactor for: 1. transmination 2. decarboxylation 3. glycongen phosphorylase 4. cystathione synthesis 5. heme synthesis 6. synthesis of niacin from tryptophan |
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Drugs that decrease pyridoxine (2)
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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 |
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increased anion gap acidosis, hypoglycemia, ketosis, increased methymalonylic acid.
suspect? |
Methylmalnonylic acidemia due to deficiency in Isomerase
Isomerase: methylmalony-Coa --> succinyl-CoA |
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S-adenosyl-methinoine (SAM)
fxn? regeneration of SAM requires? |
SAM transfers methylunit; required for NE --> E nad 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 carboxylation enzymes (add 1 carbon goup)
1. generation of oxaloacetate (for TCA or gluconeogenesis) 2. synthesis of FA chain 3. odd # FA beta oxidation |
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List 4 functions of ascorbic acid.
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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, XI, X, proteins C and S |
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What is the pathogenesis of hepatocellular steatosis seen in chronic alcoholics?
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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 wastign loss of subQ fat variable edema |
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List 3 metabolic pathways that take place in both mitochondria and cytoplasm
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HUG
Heme synthesis Urea cycle Gluconeogenesis |
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Metabolism of one glucose molecule results in how many ATPs?
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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.
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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.
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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 |
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Pyruvate kinase deficiency
sxs? |
Pyruvate kinase is used for making pyruvate
hemolytic anemia due to inability to maintain Na/K pump |
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What inhibits lipoic acid, presents with vomiting, rice water stools, garlic breath?
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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) |
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Cori cycle
fxn? energy cost? |
Transfers Lactate from muscle, RBC to the liver for gluconeogenesis. Glucose produced is moved back the tissue for glycolysis.
costs 4 ATPs |
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TCA cycle
how many ATPs are generated per cycle? list 2 irreversible enzymes |
3 NADH, 1 FADH, 1 GTP = 12 ATPs per cycle
alpha-ketoglutarate dehydrogenase Isocictrate dehydrogenase |
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How is the NADH made from glycolysis is transferred for electron transport chain?
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Muscle: glycerol-3p shuttle
Heart, liver: 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 |
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CN-, CO poisoning
How do they affect oxidative phosphorylation? |
direct electron transport inhibitors
a decrease in proton gradient and block ATP synthesis |
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2,4 DNP
how does it affect oxidative phosphorylation? what endogenous substance has a similar property? |
uncoupling agent
increased permeability of membrane --> decreased proton gradient but increased O2 consumption. ATP synthesis stops but electron transport chain continues --> generates heat thermogenin in brown fat |
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List 3 potential substrates for gluconeogenesis.
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Propyl-CoA (from odd-chain FA)
Oxaloacetate Alanine |
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List 4 Irreversible enzymes for gluconeogenesis.
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Pathway Produces Fresh Glucose
Pyruvate carboxylase (biotin) PEP carboxylase Fructose-1,6-bisphosphatase Glucose-6-phosphatase |
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What type of FA can enter gluconeogenesis? why
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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 |
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What is the purpose of HMP shunt
Energy cost? |
aka Pentose phosphate pathway
to generate NADPH for various reactions and F6P, G3P for glycolysis zero ATP used |
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List 2 main enzymes for HMP shunt?
Rate limiting step? cofactor used? |
Glucose-6-phosphate dehydrogenase (G6PD): rate-limiting
transketolase: requires B1 |
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Glucose-6-phosphate dehydrogenase (G6PD) is used for what 2 processes?
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pentose phosphate pathway (HMP shunt)
detoxification of oxidative free radicals (esp in macrophages) |
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NADPH deficiency
what disease? findings? |
chronic granulomatous disease
recurrent infection with catalase + organisms (Staph aureus, E coli, aspergeillus etc) |
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G6PD defiency
findings? inheritance pattern? |
Intrinsic hemolytic anemia (normocytic), bite cells, Heinz bodies
due to inability to detoxify free radicals X-linked recessive |
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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 |
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Infantile cataracts, jaundice, hepatomegaly, Mental retardation
dx? defect? milder form? |
Galatosemia due to galactose-1p uridyl transferase defiency
galatokinase deficiency: milder form |
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solbitol dehydrogenase
accumulated substance? affected tissues? unaffected tissues? affected group? |
Sorbitol accumulation (glucose -> sorbitol by aldolase reductase)
affected tissues: kidney, peripheral nerves, retina, lens unaffected tissue: liver, ovaries, seminal vesicles common in chronic DM pts |
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why are liver, ovaries, and seminal vesicles unaffected by sorbitol accumulation?
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due to sorbitol dehydrogenase, which converts sorbitol to fructose
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lactase deficiency
sxs? where is the enzyme located? |
lactase is a brush-border enzyme in the small intestine
bloating, cramps, osmotic diarrhea |
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List 4 glucogenic amino acids.
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MAV H
Met Arg Val His |
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List 4 amino acids that are both glucogenic and ketogenic.
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PITT
Phe Ile Thr Trp |
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List 2 amino acids that are ketogenic
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Lysine, Leucine
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What 2 amino acids are needed for growth?
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Arg and His
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List 2 amino acids that are major components of histone.
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Arg and Lys (+ molecules)
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List 2 sources of nitrogen groups on urea.
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Ammonium (NH4+)
Aspartate |
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NAG synthase defiency.
What metabolic pathway is affected? how? |
urea cycle
NAG activates carbamoyl phosphate synthetase I, which is the rate-limiting enzyme for the urea cycle |
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what 2 urea cycle enzymes are in the mitochondria?
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Carbamoyl phosphate synthetase I
Ornithine transcarbamoylase |
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What transports NH3 from peripheral tissue to liver for eventual metabolism and excretion?
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alanine
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what amino acid acts as an NH3 carrier inside the cell?
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glutamate
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Hyperammonemia
What metabolic pathway is inhibited as a result of increased NH3? why? |
TCA cycle is inhibited b/c excess NH4+ depletes alpha-ketoglutarate
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2 drugs used to tx hyperammonemia.
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Benzoate
Phenybutyrate both bind to AA and lead to excretion |
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Increased orotic acid
list 2 ddx. |
defect in orotic acid -> IMP in de novo pyrimidine synthesis
ornithine transcarbamoylase deficiency (OTC) |
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Ornithing transcarbamoylase deficiency (OTC)
inhibited metabolic process? findings? |
urea cycle is inhibited
increased orotic acid, hyperammonemia, decreased BUN |
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4 amino acid derivatives that require B6 as a cofactor?
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Niacin
Histamine Porphyrin --> heme GABA |
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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 |
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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 |
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Mental retardation, growth retardation, fair skin, eczema, musty body odor
dx? tx? |
Phenyketouria
decreased phenylalanine and increased tyrosine in the diet |
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List 2 causes of phenylketouria.
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decreased phenylalanine hydroxylase
decreased BH4 (a cofactor for Phe hydroxylase) |
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Alkaptouria
deficiency? what pathway is affected? |
congenital deficiency in homogenistic acid oxidase in the degradative pathway of tyrosine
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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 |
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what special genetic feature does albinism have?
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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? |
Homocytinuria due to:
Cystathionine synthase deficiency decreased affinity cystathione synthase for B6 OR homocysteine methylase transferase deficiency |
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Cystic kidney stone
common cause? tx? |
hereditary defect of renal tubular AA transporters for cysteine, ornithine, lysine, and arginine in the PCT
tx: acetazolamide to alkaline 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 |
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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 II 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 myogloburia with exercise
dx? defect? |
McArdle's disease
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? |
Goucher'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: 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 be 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 of 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, 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? |
hyerpchylomicronemia (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 |
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HMG-CoA reductase
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. hepatitis |
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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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