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252 Cards in this Set
- Front
- Back
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only histone that is not in the nucleosome core
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H1 - ties nucleosome beads together in a string
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required for purine synthesis
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glycine
aspartate glutamine THF |
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ribose-5-phosphate + PRPP
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forms IMP - beginning of purine synthesis
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made from orotate precursor
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pyrimidines
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what two pathways is carbamoyl phosphate involved with
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de novo pyrimidine synthesis
urea cycle |
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two drugs that inhibit dihydrofolate reductase
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methotrexate
trimethoprim |
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drug that inhibits thymidylate synthase
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5-fluorouracil
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drug that blocks de novo purine synthesis
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6-mercaptopurine
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inhibits ribonucleotide reductase
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hydroxyurea
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converts dUMP to dTMP
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N5N10 methylene THF
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methylates THF to form N5N10 methylene THF
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B12
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findings seen if unable to convert orotic acid to UMP (de novo pyrimidine synthesis)
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orotic aciduria
megaloblastic anemia that doesn't improve with B12 or folic acid failure to thrive |
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treatment of orotic aciduria
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oral uridine administration
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this deficiency leads to feedback inhibition of ribonucleotide reductase (forms deoxyribonucleotides)
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excess ATP and dATP due to adenosine deaminase deficiency - inhibits DNA synthesis leading to SCID
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what does absence of HGPRT lead to
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inability to convert hypoxanthine to IMP and guanine to GMP - results in excess uric acid production
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findings associated with defective HGPRT
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retardation, self-mutilation, aggression, hyperuricemia, gout:
Lesch-Nyhan syndrome |
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final common pathway of purine breakdown
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uric acid from xanthine via xanthine oxidase
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prevents DNA strands from reannealing
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single-stranded binding proteins
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creates a nick in the helix to relive supercoils created during replication
what drug inhibits this |
DNA topoisomerase
fluoroquinolones (specific for prokaryotic) |
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job of primase
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makes an RNA primer for DNA polymerase III to initiate replication
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which side does one always add deoxynucleotides to
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3'
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does prokaryotic deoxynucleotide synthesis and has 3' - 5' exonuclease activity
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DNA polymerase III
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which side of the DNA is the nucleotide always added
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3' end no matter what
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degrades prikaryotic RNA primer and fills in the gap with DNA
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DNA polymerase I
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excises the RNA primer with 5' - 3' exonuclease activity
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DNA polymerase I
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associated with specific endonuclease recognizing damaged bases - mutated in xeroderm pigmentosum
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nucleotide excision repair
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DNA repair mechanism associated with AP endonuclease that cuts DNA at apyrimidinic site
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base excision repair
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unmethylated, newly synthesized DNA is recognized and mismatched nucleotides are removed is known as mismatch repair - what is the associated disease if mutated
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hereditary nonpolyposis colorectal cancer
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which direction is DNA and RNA synthesized in
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5' --> 3' (N --> C)
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how do drugs block DNA replication
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they have modified 3' OH preventing addition of the next nucleotide
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mRNA start codon
what does it code for |
AUG - methionine
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inhibits RNA polymerase II, found in death cap mushrooms
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alpha-amanitin
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Eurkaryotic RNA polymerase
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I - rRNA
II - mRNA III - tRNA |
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Prokaryotic RNA polymerase
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1 RNA polymerase that is a multisubunit complex makes all 3 kinds of RNA
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3 things for the process that makes DNA transcript into a mRNA
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1. 5' capping (7-mthylguanosine)
2. polyadenylation on 3' end 3. splicing out introns |
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what do patients with lupus make antibodies against
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spliceosomal snRNPs
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which end of the tRNA binds the amino acid
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3' end with CCA codon as it's 3' end
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what is the tRNA wobble
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accurate base pairing is required only in the first 2 nucleotide positions, the 3rd can differ and still code for the same amino acid
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antibiotic that prevents attachment of aminoacyl-tRNA to the 30S subunit
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tetracyclines
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what activates initiation of translation of mRNA
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GTP hydrolysis activate initiation factors to assemble the 40S (30S) ribosomal subunit
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antibiotic that inhibits formation of the initiation complex and cause misreading of mRNA
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aminoglycosides
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what do Rb and p53 normally inhibit
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G1-to-S progression
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cells that never go to G0, divide rapidly
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bone marrow, gut epithelium, skin
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cells that remain in G0, regenerate from stem cells
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neurons, skeletal/cardiac muscle, RBCs
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RER in neurons
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Nissle bodies
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cells that are rich in RER
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mucus-secreting goblet cells of small intestine
antibody-secreting plasma cells |
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cells that are rich in SER
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liver hepatocytes
steroid hormone-producing adrenal cortex cells |
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inherited lysosomal storage disorder
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failure of addition of mannose-6-phosphate to lysosome proteins - enzymes are secreted outside the cell instead of being targeted to lysosomes
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helps traffic things to the lysosome via trans-Golgi or receptor-mediated endocytosis
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clathrin
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differentiate dynein and kinesin
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dynein - retrograde microtubule transport (+ --> -)
kinesin - anterograde microtubule transport (- --> +) ** - is the center of the cell |
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microtubule polymerization defect resulting in decreased phagocytosis
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Chediak-Higashi syndrome
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disease associated with immotile cilia due to a dynein arm defect
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Kartagener's syndrome:
infertility, bronchiectasis, recurrent sinusitis, situs inversus |
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examples of intermediate filaments
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vimentin, desmin, cytokeratin, glial fibrillary acid proteins (GFAP), neurofilaments
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immunohistochemical stains:
vimentein desmin cytokeratin GFAP neurofilaments |
vimentin - CT
desmin - muscle cytokeratin - epithelial cells GFAP - neuroglia neurofilaments - neurons |
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cilia structure
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9+2 arrangement of microtubules
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inhibits the Na/K ATPase by binding to K site
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Ouabain
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enhances cardiac contractility by inhibiting Na/K ATPase directly which indirectly inhibits the Na/Ca exhange - increases intracellular Ca
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Cardiac glycosides (Digoxin)
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differentiate different types of collagen
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type I - Bone, Skin, tendon
type II - cartilage type III - reticulin (blood vessels, uterus, granulation tissue) type IV - basement membrane |
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what is required to hydroxylate proline or lysine residues for collagen synthesis
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vitamin C
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residue found in collagen that is both hydroxylated and glycosylated
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lysine
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inability to for triple helix procollagen
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osteogenesis imperfecta
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most frequently affected collagen in Ehlers-Danlos syndrome
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type III
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collagen affect by osteogenesis imperfecta: signs
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type I collagen - multiple bone fractures, blue sclerae, hearing loss, dental imperfections (lack of dentin)
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disease associated with type IV collagen defect leading to nephritis and deafness
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Alport's syndrome
|
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normally inhibits elastase
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a1-antitrypsin
|
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defect in fibrillin
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Marfan's syndrome
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differences in phenotype depend on whether the mutation is of maternal or paternal origin (Prader-Willi and Angelman's syndromes)
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imprinting
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the prevalence of an X-linked recessive disease with hardy-weinberg equilibrium
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males = q
females = q^2 *p^2 + 2pq + q^2 = 1 |
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X-linked dominant
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all female offspring of the affected father are diseased
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All offspring of affected female show signs of disease
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mitochondrial inheritance
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Only females are carriers, no male-to-male transmission
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X-linked recessive
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hypophosphatemic rickets
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X-linked dominant disorder that results in phosphate wasting at proximal tubule
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degeneration of retinal ganglion cells and axons leading to acute loss of central vision
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Leber's hereditary optic neuropathy - mitochondrial inheritance
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associated with heteroplasmy
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mitochondrial inherited disorders - contain both normal and mutated MtDNA
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familial hypercholesterolemia
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defective or absent LDL receptor, atherosclerotic disease, tendon xanthomas (Achilles), MI before age 20
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inherited disorder of blood vessels, associated with: telangiectasia, recurrent epistaxis, AV malformations
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hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
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what does the CFTR channel do
|
actively secrete Cl in lungs and GI tract and reabsorb Cl from sweat
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associated with cafe-au-lait spots, neural tumors, and pigmented iris hamartomas
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Neurofibromatosis type 1
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associated with bilateral acoustic schwannomas ans juvenile cataracts
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Neurofibromatosis type 2
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associated with adenoma sebaceum (red papules on face), hypopigmented spots, mental retardation, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytoma
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Tuberous sclerosis
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pregnancy quad screen in fetus with down syndrome:
aFP B-hCG estriol inhibin A |
decreased aFP
decreased estriol increased B-hCG increased inhibin A |
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associated with nuchal translucency
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Down' syndrome
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chromosomes associated with Robertsonian translocation
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13,14,15, 21, 22
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2 22q11 deletion syndromes
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DiGeorge syndrome - thymic, parathyroid, and cardiac
Velocardiofacial syndrome - palate, facial, and cardiac |
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vitamin associated with being an antioxidant and involved in collagen synthesis
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Vitamin C
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fat soluble vitamins
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A,D,E, K
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what disorders can result in fat-soluble vitamin deficiencies
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CF
celiac disease |
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deficiency of this vitamin results in night blindness and dry skin
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Vitamin A
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vitamin essential for normal differentiation of epithelial cells into specialized tissue, used to treat measles
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vitamin A
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what four enzymes if thiamin a cofactor for
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1. pyruvate dehydrogenase
2. a-ketoglutarate dehydrogenase 3. transketolase (HMP shunt) 4. branched-chain AA dehydrogenase |
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differentiate dry and wet berberi (B1 deficiency - thiamin)
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dry beriberi - polyneuritis and symmetrical muscle wasting
wet beriberi - high-output cardiac failure and edema |
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glucose infusion can worsen deficiency in this vitamin
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Thiamin - B1
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deficiency in this vitamin is associated with cheilosis (inflammation of lips, scaling and fissures at corners of mouth) and corneal vascularization
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Riboflavin (B2)
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this vitamin is derived from tryptophan and requires B6 for synthesis
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niacin (B3)
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clinical presentation of niacin deficiency (pellagra)
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glossitis
diarrhea dermatitis dementia |
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three way in which one can get niacin deficiency
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1. Hartnup disease (decreased tryptophan absorption)
2. malignant carcinoid syndrome (increase tryptophan metabolism) 3. decreased B6 (INH) |
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facial flushing is seen in treatment of hyperlipidemia with this vitamin
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niacin
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essential componenet of CoA
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pantothenate (B5)
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this vitamin is converted to pyridoxal phosphate (PLP) and used as cofactor for transamination, glycogen phosphorylase, and heme synthesis
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pyridoxine (B6)
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deficiency in this vitamin results in peripheral neuropathy and sideroblastic anemias
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pyridoxine (B6)
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cofactor for homocystein methyltransferase using THF as CH3 carrier
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cobalamin (B12)
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two reactions B12 is involved in
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homocysteine + N-methyl THF --> Methionine + THF
Methylmalonyl CoA --> Succinyl-CoA |
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causes of Vitamin B12 deficiency
|
malabsorption (celiac, Diphyllobothrium latum)
pernicious anemia (lack intrinsic factor) Crohn's disease (lack ileum) |
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coenzyme for 1-carbon transfer, important for synthesis of nitrogenous bases
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folate
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where is folate and B12 primarily stored
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liver
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ATP + methionine =
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SAM
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regeneration of methionine (thus SAM) is dependent on what
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folate
B12 |
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3 reactions in which biotin is a cofactor
|
1. pyruvate carboxylase (pyruvate --> oxaloacetate)
2. acetyl-CoA carboxylase (acetyl-CoA --> malonyl-CoA) 3. propionyl-CoA carboxylase (propionyl-CoA --> methylmalonyl-CoA) |
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deficiency associated with excessive ingestion of raw eggs
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biotin
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3 functions of vitamin C
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1. keep iron in reduced state (Fe 2+)
2. hydroxylation of proline and lysine 3. necessary for dopamin B-hydroxylase which convertes dopamine to NE |
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associated with swollen gums, bruising, hemarthrosis, and poor wound healing
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scurvy - vitamin C deficiency
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storage and active form of Vitamin D
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storage - 25-OH D3
active - 1,25-OH D3 |
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this vitamin protects erythryocytes and membranes from free-radical damage
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Vitamin E
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decrease in this vitamin results in: hemolytic anemia, muscle weakness, posterior column and spinocerebellar tract demyelination
|
Vitamin E
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this vitamin is synthesized by intestinal flora - neonates are given injection at birth
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Vitamin K
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vitamin deficiency associated with increased PT and aPTT but normal bleeding time
|
vitamin K deficiency
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deficiency in this substance is associated with delayed wound healing, hypogonadism, and anosmia
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Zinc
|
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this drug inhibits acetaldehyde dehydrogenase leading to accumulation of acetaldehye
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Disulfiram
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this enzyme operates via zero-order kinetics and uses NAD as limiting reagent
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alcohol dehydrogenase
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this drug inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning
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fomepizole
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ethanol metabolism increases NADH/NAD ratio in liver causing what to happen
|
pyruvate --> lactate and oxaloacetate --> malate
*both turn NADH --> NAD+ **gluconeogenesis is inhibited and fatty acid synthesis is stimulated |
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child presents with malnutrition, edema, anemia, and swollen belly (fatty liver due to decreased apolipprotein synthesis)
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Kwashiorkor - protein malnutrition
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child presents with tissue and muscle wasting due to malnutrition
|
Marasmus - energy malnutrition
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3 biochemical cycles that take place in both cytoplasm and mitochondria
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1. heme synthesis
2. urea cycle 3. gluconeogenesis |
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enzyme terminology:
kinase phosphorylase phosphatase dehydrogenase carboxylase |
1. kinase - uses ATP to add phosphate group
2. phosphorylase - adds phosphate without using ATP 3. phosphatase - remove phosphate group 4. dehydrogenase - oxidizes substrate 5. carboxylase - adds 1 carbon with help of biotin |
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differentiate amount of ATP produced via malate-aspartate shuttle (heart and liver) vs. glycerol-3-phosphate shuttle (muscle)
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malate-aspartate - 32 ATP
glycerol-3-phosphate - 30 ATP |
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product of the HMP shunt
|
NADPH
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what is NADPH used for
|
1. anabolic processes (steroid and fatty acid synthesis)
2. oxidative burst 3. P-450 4. glutathione reductase |
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where is hexokinase and glucokinase found respectively
|
hexokinase - ubiquitous
glucokinase - liver and B cells of pancreas |
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differentiate hexokinase vs. glucokinase in affinity (Km) and capacity (Vmax)
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hexokinase - high affinity (low Km) and low capacity (low Vmax)
glucokinase - low affinity (high Km) and high capacity (high Vmax) |
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what is hexokinase inhibited by
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feedback inhibition by glucose-6-phosphate
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rate-limiting step of glycolysis
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PFK-1
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what activates and inhibits PFK-1
|
AMP and F-2,6-BP activate
ATP and Citrate inhibit |
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|
differentiate PFK-2 in fasting state vs. fed state
|
fasting state - decreased PFK-2 therefore not making F-2,6-BP to activate PFK-1 and glycolysis
fed state - increased PFK-2 *glucagon decreases PFK-2 by decreases cAMP and PKA **insulin increases PFK-2 via cAMP and PKA |
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5 cofactors of the pyruvate dehydrogenase complex
|
thiamin
FAD NAD CoA Lipoic acid |
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which substance inhibits lipoic acid and results in vomiting, rice water stools, and garlic breath
|
Arsenic
|
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two purely ketogenic amino acids
|
Lysine
Leucine |
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deficiency of this enzyme results in increased alanine and pyruvate and neurologic defects
|
pyruvate dehydrogenase deficiency (congenital or seen in alcoholics)
|
|
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treatment of PDH deficiency
|
increase intake of ketogenic nutrients (high fat content of lysine and leucine)
|
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4 different pyruvate metabolic pathways
|
1. lactate - end of anaerobic glycosis
2. alanine - carries amino groups to liver from muscle 3. oxaloacetate - can replenich TCA cycle 4. acetyl-CoA for TCA cycle |
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three products of PDH
|
Acetyl-CoA
NADH CO2 |
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products of TCA cycle
|
3 NADH
1 FADH2 2 CO2 1 GTP *(multiply by two for each glucose) |
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where is GTP and FADH2 formed in TCA cycle
|
GTP - succinyl-CoA --> succinate
FADH2 - succinate --> fumarate |
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where are the 3 NADH made in the TCA cycle
|
isocitrate --> a-ketoglutarate
a-ketoglurate --> succinyl-CoA malate --> oxaloacetate |
|
|
how do the NADH electrons from glycolysis and TCA cycle enter the mitochondria (2 ways)
|
1. malate-aspartate shuttle
2. glycerol-3-phosphate shuttle |
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where are FADH2 electrons transferred
|
complex II of electron transport chain
|
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|
ATP produced from NADH vs. FADH2
|
NADH = 3 ATP
FADH2 = 2 ATP |
|
|
electron transport inhibitor that causes decreased proton gradient and blocks ATP synthesis
|
CN
|
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mitochondrial ATPase inhibitor that causes increased proton gradient, but no ATP is produced
|
oligomycin
|
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|
increases permeability of mitochondrial membrane resulting in decreased proton gradient, increased O2 consumption, and produces heat
|
aspirin
|
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|
what does muscle lack in which it cannot participate in gluconeogenesis
|
glucose-6-phosphatase
|
|
|
how can odd-chain fatty acids serve as glucose source
|
yield propinoyl-CoA, this become succinyl-CoA via B12 and enters TCA. Becomes oxaloacetate which can be converted to phosphoenolpyruvate (PEP carboxykinase) and enter gluconeogenesis
|
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oxidative (irreversible) reaction of HMP shunt; enzyme and products
|
G6PD - yeilds CO2, 2 NADPH, Ribulose-5-P
|
|
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nonoxidative (reversible) reaction of HMP shunt; enzyme and products
|
Transketolase (uses ribulose-5-P and requires B1) - yields Ribose-5-P, G-3-P, F-6-P
|
|
|
enzyme deficiency seen in chronic granulomatous disease
|
NADPH oxidase
|
|
|
enzyme that uses NADPH and forms O2 radicals
|
NADPH oxidase
|
|
|
enzyme that forms H2O2 from O2 radicals
|
superoxide dismutase
|
|
|
enzyme that combines H2O2 and Cl forming hypochlorite (bleach) which destroys bacteria
|
myeloperoxidase
|
|
|
where does respiratory burst (oxidative burst) take place
|
Neutrophils and macrophages
|
|
|
Patients with chronic granulomatous disease are at increased risk of infection by organisms that are
|
catalse-positive - because they neutralize their own H2O2
*because these patients cannot form H2O2, they can only use the H2O2 generated by invading organisms |
|
|
this enzyme is necessary for detoxify free radicals and peroxidases, these patients are susceptibel to oxidizing agents
|
G6PD
|
|
|
oxidized hemoglobin precipitated within RBC
|
Heinz body
|
|
|
results from phagocytic removal of Heinz bodies by macrophages
|
Bite cells
|
|
|
keeps glutathione in reduced form to defend against oxidizing agents
|
NADPH
|
|
|
this monosaccharide bypasses the rate-limiting step of glycolysis
enzymes involved |
Fructose
Fructokinase forms F-1-P, Aldolase B forms DHAP and Glyceraldehyde *both go to glyceraldehyde-3-P and enter glycolysis |
|
|
enzyme associated with classic galactosemia
|
galactose-1-phosphate uridyltransferase
|
|
|
product of galactose-1-phosphate uridyltransferases
|
glucose-1-P and UDP-galactose
|
|
|
tissues lacking what enzyme are at increased risk for intracellular sorbitol accumulation
|
sorbitol dehydrogenase (forms fructose from sorbitol)
|
|
|
what can sorbitol accumulation lead to
|
cataracts
retinopathy peripheral neuropathy |
|
|
loss of brush-border enzymes that may follow gastroenertitis
|
lactase deficiency
|
|
|
two AA required during periods of growth that bind negatively charged DNA
|
Arginine
Histadine |
|
|
rate-limiting step of urea cycle
|
carbamoyl phosphate synthetase I (CO2 + NH4 + 2 ATP --> carbamoyl phosphate)
|
|
|
AA that donates ammonia to urea cycle
|
aspartate
Citrulline + aspartate --> argininosuccinate |
|
|
excess in this substance deplete a-ketoglutarate leading to inhibition of TCA cycle
|
hyperammonemia
|
|
|
most common urea cycle disorder
|
ornithine transcarbamoylase deficiency (x-linked recessive)
|
|
|
associated with orotic acid in blood and urine, decreased BUN, and symptoms of hyperammonemia
|
ornithine transcarbamoylase deficiency
|
|
|
pathway of phenylalanine use
|
phenylalanine --> tyrosine --> DOPA --> dopamine --> NE --> E
|
|
|
what is tryptophan used to make
|
Niacin
Serotonin Melatonin |
|
|
what is glycine used to make
|
Heme
|
|
|
what is formed in dihydropterin reductase THB --> DHB (needed for both phenylalanine and tyrosine hydroxylase)
|
NADPH
|
|
|
vitamin needed for conversion of dopamine to norepinephrine
|
vitamin C
|
|
|
needed for conversion of NE --> E
|
SAM
|
|
|
new essential amino acid seen in phenylketonuria
|
tyrosine
|
|
|
two causes for phenylketonuria
|
1. deficient phenylalanine hydroxylase
2. deficient tetrahydrobiopterin cofactor |
|
|
associated with mental retardation, growth retardation, seizures, and musty body odor
|
phenylketonuria
|
|
|
treatment for phenylketonuria
|
decreased phenylalanine and increase tyrosine in diet
|
|
|
congenital deficiency of homogentisic acid oxidase
|
alkaptonuria
|
|
|
congenital deficiency of what enzyme in the degredative pathway of tyrosine to fumarate leads to dark CT, brown pigmented sclera, and urine turning black on standing
|
homogentisic acid oxidase
|
|
|
two congenital deficiencies associated with albinism
|
tyrosinase deficiency
defective tyrosin transporters |
|
|
three forms of homocystinuria
|
1. cystathionine sythase deficiency
2. decreased affinity of cystathionine for pyridoxal phosphate (B6) 3. homocystein methyltransferase deficiency |
|
|
degredative pathwhay of homocysteine
|
homocystein --> cystathionine (cystathionine synthase) --> cysteine
|
|
|
cofactor for cysthionine synthase (homocysteine --> cystahionine)
|
B6
|
|
|
a hereditary defect in what can lead to the precipitation of cystine kidney stones
|
renal tubular amino acid transporter in PCT
*also needed for ornithine, lysine, and arginine |
|
|
treatment for cystinuria
|
acetazolamine to alkalinize the urine
|
|
|
maple syrup urine disease
|
blocked degradation of branched amino acids due to deficiency in a-ketoacid dehydrogenase
|
|
|
associated with increased a-ketoacids in the blood, Isoleucine, Leucine, and Valine
|
maple syrup urine disease
|
|
|
this defect amino acid transporter in renal epithelial cells leads can lead to deficiency in tryptophan and lead to pellagra
|
Hartnup disease
|
|
|
glycogen regulation by insulin vs. glucagon/epinephrine
|
glucagon/epi - leads to phosphorylation of glycogen phorphorylase
insulin - leads to dephosphorylation of glycogen phosphorylase |
|
|
storage form of glucose in glycogen molecule
|
UDP-glucose - derived from glucose-1-P
|
|
|
what does lysosomal a-1,4-glucosidase do
|
degrade small amount of glycogen
|
|
|
4 glycogen storage diseases and corresponding enzyme deficiency
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von Gierke's disease - glucose-6-phosphatase
Pompe's disease - lysosomal a-1,4-glucosidase Cori's disease - debranching enzyme (a-1,6-glucosidase) McArdle's disease - skeltal muscle glycogen phosphorylase |
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glycogen storage disease associated with severe hypoglycemia, increased glycogen in the liver leading to hepatomegaly, and increased blood lactate
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von Gierke's disease - glycose-6-phosphatase
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glycogen storage disease associated with cardiomegaly
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Pompe's disease - lysosomal a-1,4-glucosidase
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glycogen storage disease associated with fasting hypoglycemia, increased glycogen in liver, but normal blood lactate
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Cori's disease - debranching enzyme
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glycogen storage disease associated with increased glycogen in muscle leading to painful cramps and myoglobinuria with strenuous exercise
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McArdle's disease - skeletal muscle glycogen phosphorylase
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accumulated substrate and deficient enzyme in Fabry's disease
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substrate - ceremide trihexoside
enzyme - a-galactosidase A |
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accumulated substrate and deficient enzyme in Gaucher's disease
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substrate - glucocerebroside
enzyme - B-glucocerebrosidase |
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accumulated substrate and deficient enzyme in Niemann-Pick disease
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substrate - sphingomyelin
enzyme - sphingomyelinase |
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accumulated substrate and deficient enzyme in Tay-Sachs disease
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substrate - GM2 ganglioside
enzyme - Hexosaminidase A |
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accumulated substrate and deficient enzyme in Krabbe's disease
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substrate - Galactocerebroside
enzyme - galactocerebrosidase |
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accumulated substrate and deficient enzyme in metachromatic leukodystrophy
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substrate - cerebroside sulfate
enzyme - arylsulfatase A |
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most common lysosomal storage disease
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Gaucher's disease
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lysosomal storage disease associated with peripheral neuropathy, angiokeratomas, CV/renal disease
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Fabry's disease
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lysosomal storage disease associated with hepatosplenomegaly, aspetic necrosis of femur, and macrophages that look like crumpled tissue paper
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Gaucher's disease
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lysosomal storage disease associated with progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, and foam cells
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Niemann-Pick disease
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lysosomal storage disease associated with peripheral neuropathy, developmental delay, optic atrophy, and globoid cells
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Krabbe's disease
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lysosomal storage disease associated with progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin
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Tay-Sachs disease
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lysosomal storage disease associated with central and peripheral demyelination with ataxia and dementia
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Metachromatic leukodystrophy
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accumulated substrate and deficient enzyme in Hurler's syndrome
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substrate - heparan sulfate, dermatan sulfate
enzyme - a-iduronidase |
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accumulated substrate and deficient enzyme in Hunter's syndrome
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substrate - heparan sulfate, dermatan sulfate
enzyme - iduonate sulfatase |
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lysosomal storage disease associated with developmental delay, gargoylism airway obstruction, corneal clouding, hepatosplenomegaly
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Hurler's syndrome
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lysosomal storage disease associated with aggressive behavior, milder form of Hurler's with no corneal clouding
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Hunter's syndrome
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deficiency in this substance results in weakness and hypoketotic hypoglycemia
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carnitine deficiency
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what inhibits the transfer of acyl-CoA across the carnitine shuttle
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Malonyl-CoA
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shuttle acetyl-CoA uses to move out of mitochondria for fatty acid synthesis
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citrate shuttle
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which ketone body cannot be detected in the urine
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B-hydroxybutyrate
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associated with fruity odor on breath
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acetone from ketoacidosis
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what happens to oxaloacetate during prolonged starvation and ketoacidosis
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depleted for gluconeogenesis - stall TCA cycle and shunts glucose and FFA toward the production of ketone bodies
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when is glycogen reserve depleted during starvation
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1 day
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major contributor to making glucose during fasting between meals
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hepatic glycogenolysis
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rate limiting step in cholesterol synthesis
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HMG-CoA reductase
HMG-CoA --> mevalonate |
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enzyme that degrades circulating TG in chylomicrons and VLDLs
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lipoprotein lipase
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enzyme that degrades TG remaining of IDL
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hepatic TG lipase
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enzyme that degrades TG stored in adipocytes
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hormone-sensitive lipase
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enzyme that catalyzes esterification of cholesterol and forms mature HDL from nascent HDL
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lecithin-cholesterol acyltransferase (LCAT)
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this enzyme mediates transfer of cholesterol esters to VLDL, IDL, and LDL from HDL molecule
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cholesterol ester transfer protein (CETP)
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apolipoprotein that activates LCAT
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A-I - found on HDL
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apolipoprotein that binds to LDL receptor
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B-100
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apolipoprotein that is a cofactor for lipoprotein lipase
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C-II
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this apoplipoprotein mediates chylomicron secretion
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B-48
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delivers dietary TG to peripheral tissue, secreted by intestinal epithelial cells
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chylomicron
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delivers hepatic TG to peripheral tissue, secreted by liver
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VLDL
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formed in the degredation of VLDL, delivers triglycerides and cholesterol to liver why they are degraded to LDL
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IDL
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delivers hepatic cholesterol to peripheral tissue, taken up by target cell via receptor-mediated endocytosis
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LDL
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mediates reserve cholesterol transport from peripheral to liver, acts as repository for ApoC and ApoE
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HDL
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hyperchylomicronemia is associated with what deficiency
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lipoprotein lipase or altered apolipoprotein C-II
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hyperchylomicronemia can result in what problems
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pancreatitis, hepatosplenomegaly, xathomas
*no increase risk for atherosclerosis |
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what is deficient in familial hypercholesterolemia
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LDL receptors resulting in increased LDL and cholesterol
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this dyslipidemia can result in accelerated atherosclerosis, xanthomas, and corneal arcus
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familial hypercholesterolemia - deficient LDL receptors
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hypertriglyceridemia
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hepatic overproduction of VLDL leading to pancreatitis
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this patient presents with intestinal biopsy with accumulations of lipid within enterocytes; associated with failure to thrive, steatorrhea, ataxia, acanthocytosis (spiked RBCs)
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abetalipoproteinemia
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hereditary inability to synthesize ApoB100 or ApoB48
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abetalipoproteinemia
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