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462 Cards in this Set
- Front
- Back
|
what metabolism goes on in the mitochondria?
|
- fatty acid oxidation (beta-oxidation)
- acetyl-CoA production - TCA cycle - oxidative phosphorylation |
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|
what metabolism goes on in the cytoplasm?
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- glycolysis
- fatty acid synthesis - HMP shunt - protein synthesis (RER) - steroid synthesis (SER) |
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what metabolism goes on in both the cytoplasm & mitochondria?
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"HUGs take 2"
- heme synthesis - urea cycle - gluconeogenesis |
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rate determining enzyme of glycolysis
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phosphofructokinase-1 (PFK-1)
|
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rate determining enzyme of gluconeogenesis
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fructose-1,6-bisphosphatase
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rate determining enzyme of TCA cycle
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isocitrate dehydrogenase
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rate determining enzyme of glycogen synthesis
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glycogen synthase
|
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rate determining enzyme of glycogenolysis
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glycogen phosphorylase
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rate determining enzyme of HMP shunt
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glucose-6-phosphate dehydrogenase (G6PD)
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rate determining enzyme of de novo pyrimidine synthesis
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carbamoyl phosphate synthetase II (CPS2)
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rate determining enzyme of de novo purine synthesis
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glutamine-PRPP amidotransferase
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rate determining enzyme of urea cycle
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carbamoyl phosphate synthetase I (CPS1)
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rate determining enzyme of fatty acid synthesis
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acetyl-CoA carboxylase (ACC)
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rate determining enzyme of fatty acid oxidation
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carnitine acyltransferase I
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rate determining enzyme of ketogenesis
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HMG-CoA synthase
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rate determining enzyme of cholesterol synthesis
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HMG-CoA reductase
|
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rate determining enzyme of heme synthesis
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aminolevulinic synthase
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rate determining enzyme of bile acid synthesis
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7-alpha-hydroxylase
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results in excess NH4+ which depletes alpha-ketoglutarate, l/t inhibition of the TCA cycle
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hyperammonemia
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tx for hyperammonemia
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- limit protein in diet
- to tx urea cycle enz def: benzoate or phenylbutyrate (both bind AA & l/t excretion) - to tx liver dz: lactulose |
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MOA of lactulose
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lactulose+bacteria creates acidic pH → traps ammonia in gut
also pulls NH4 from blood to excr |
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DNA is (pos/neg) charged.
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negative
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histone octamers consist of what amino acids?
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lysine & arginine
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Histone octamers are (pos/neg) charged.
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positive
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histone octamer consists of...
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2 sets of:
- H2A - H2B - H3 - H4 |
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cytosine→ uracil is a ___ reaction
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deamination
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(A-T/G-C) has a higher melting temp
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G-C (3 H bonds)
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purine sources of carbon
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- CO2
- Glycine - N10-formyl-tetrahydrofolate |
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pyrimidine sources of C
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- Aspartate
- CO2 + glutamine → carbamoyl phosphate |
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glutamine + CO2 + ATP → (CPS2) → ??
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carbamoyl phosphate
(RLE for pyrimidine synth) |
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RLS of pyrimidine synthesis
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Carbamoyl Phosphate Synthetase 2 (CPS2) making Carbamoyl Phosphate
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RLS of purine synthesis
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glutamine PRPP aminotransferase converting PRPP →→→ IMP
|
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hydroxyurea inhibits...
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rubonucleotide reductase
(a part of pyrimidine synth; UDP→dUDP/CTP) |
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6-mercaptopurine (6-MP) blocks...?
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de novo purine synthesis
(blocks PRPP synthetase that makes the PRPP) |
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5-fluorouracil (5-FU) inhibits...?
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thymidylate synthase
(part of pyrimidine synthesis; ↓dTMP) |
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methotrexate (MTX) inhibits...
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dihydrofolate reductase
(part of pyrimidine synthesis; ↓dTMP) |
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trimethoprim inhibits...
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bacterial dihydrofolate reductase
(part of pyrimidine synthesis; ↓dTMP) |
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clinical findings of orotic aciduria
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- ↑ orotic acid in urine
- megaloblastic anemia (doesn't improve w/B12/folate) - failure to thrive - NO hyperammonemia! (vs OTC deficiency) |
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defective enzyme in orotic aciduria
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- orotic acid phosphoribosyltransferase
- OR orotidine 5'-phosphate decarboxylase (messes up pyrimidine synth; can't convert orotic acid→UMP) |
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orotic aciduria tx
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oral uridine
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defect in Lesch-Nyhan
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defective purine salvage
no HGPRT (which converts hypoxanthine→IMP & guanine→GMP) l/t excess uric acid production |
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retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
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Lesch-Nyhan
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common enzyme deficiency resulting in SCID
|
adenosine deaminase deficiency
|
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SCID adenosine deaminase deficiency mechanism of pathology
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- ↑ATP & dATP imbalances nucleotide pool via feedback inhib of ribonucleotide reductase
- this prevents DNA synth & thus ↓ lymphocyte count |
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transition
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sub'ing purine for purine, etc
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transversion
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sub'ing purine for pyrimidine & vice versa
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"unamniguous" refers to...
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each codon specifying only 1 AA
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"degenerate" refers to...
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>1 codon coding for the same AA
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"universal" refers to...
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genetic code being conserved throughout evolution
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"missense" refers to...
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changed AA
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"nonsense" refers to...
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change resulting in an early stop codon
(stop the nonsense!) |
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helicase
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unwinds DNA template @repli fork
|
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ss-binding protein
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prevents strands from reannealing
|
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DNA topoisomerases
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creates a nick in the helix to relieve supercoils
(aka DNA gyrase) |
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BREED: CAVALIER KING CHARLES SPANIEL
Division: Toy Origin: England Purpose: Companion Helath problems: Heart disease, ear infection, eye problems and dislocating kneecaps Behavior problems: Friendly and social with both people and other dogs. easy to train. |
Characteristics:
Life Span: 9 to 11 years. Color: Blenheim: rich chestnut markings on a clear, pearly white ground; Tricolor: jet black markings on a clear pearly white ground; Ruby: solid rich red; Black and Tan: jet black with rich, bright tan markings. Coat: Moderate length, silky, free from curl; feathering on ears, chest, legs and tail Grooming: Brushing two to three times weekly, more often in shedding season; bathe every four weeks or as needed; trim nails monthly. Height: 12 to 13 inches at the withers. Weight: 13 to 18 pounds; as proportionate to height. |
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DNA polymerase I
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- proks only
- degrades RNA primer & fills w/DNA |
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DNA poly III adds in a ___ fashion.
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5'→3'
(adds to the 3' end) |
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DNA poly III "proofreads" w/...
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3'→5' exonuclease
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DNA ligase
|
seals
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DNA polymerase I excises RNA primer w/...
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5'→3' exonuclease
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1000x ↑ risk of skin cancer
|
xeroderma pigmentosum
|
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problem in xeroderma pigmentosum
|
messed up nucleotide excision repair → prevents repair of thymidine dimers
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problem in hereditary nonpolyposis colorectal cancer (HNPCC)
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messed up mismatch repair
(can't remove mismatched nucleotides) |
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types of RNA
|
rRNA = most abundant (rampant)
mRNA = longest (massive) tRNA = smallest (tiny) |
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Protonix
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Pantoprazole
|
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AUG codes for ___ in eukaryotes
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methionine
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AUG codes for ___ in prokaryotes
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formyl-methionine (f-Met)
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mRNA stop codons
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- UGA (U Go Away)
- UAA (U Are Away) - UAG (U Are Gone) |
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functional organization of a gene
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5'--[promoter]--[repressor/enhancer]--[-75 CAAT]--[-25 TATA]--[transcription initiation site]--[CODING REGION w/INTRONS & EXONS]---AATAAA--3'
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transcription factors must do what for transcription to take place?
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bind the promoter region
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promoter mutation commonly results in...
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dramatic ↓ in amount of gene transcribed
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makes rRNA / mRNA / tRNA (in eukaryotes)
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rRNA = RNA poly I (in nucleolus)
mRNA = RNA poly II (in nucleoplasm) tRNA = RNA poly III (in nucleoplasm) (but has NO proofreading functions!!) |
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makes rRNA / mRNA / tRNA (in prokaryotes)
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1 RNA poly makes all 3
|
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causes acute liver failure if ingested
|
alpha-amanitin (in death cap mushrooms)
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alpha-amanitin
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inhibits RNA poly II
(death cap mushrooms; causes liver failure if ingested) |
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inhibits RNA poly II
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alpha-amanitin / death cap mushrooms
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inhibits RNA polymerase RNA production in prokaryotes
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rifampin
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3 things that happen to get RNA out of nucleus after transcription
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1) capping on 5' end (7-methylguanosine)
2) polyadenylation on 3' end (~200 A's) 3) splicing out of introns |
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ONLY ___ RNA is transported out of the nucleus.
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processed
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before a transcript becomes mRNA it is called:
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heterogenous nuclear RNA (hnRNA)
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a capped & tailed transcript is called:
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mRNA
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polyadenylation signal:
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AAUAAA
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poly-A polymerase (does/does not) require a template.
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does not
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enzyme that does pre-mRNA splicing
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spliceosome
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patients w/lupus make antibodies to what proteins used in mRNA synth?
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spliceosomal snRNP's
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introns vs exons
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INtrons stay IN
EXsons EXit & are EXpressed |
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the AA is put on what end of the tRNA?
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3' OH end!!
|
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what enzyme puts the AA on the tRNA?
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aminoacyl-tRNA synthetase
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what med binds to tRNA & prevents the attachment of aminoacyl-tRNA?
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tetracyclines
(bind the 30S subunit) |
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aminoacyl-tRNA binds to __ site.
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A site
(tetracyclins bind to the 30S subunit to block this) |
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catalyzes peptide bond formation & transfers growing polypeptide to AA in A site
(protein synth) |
ribosomal rRNA (aka "ribozyme")
(the transfer is by peptidyl transferase) |
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peptidyl transferase
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transfers growing polypep to AA in A site during protein synth
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eukaryotes: __S + __S → __S ??
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40S + 60S → 80S
(Euks = Even) |
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prokaryotes: __S + __S → __S ??
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30S + 50S → 70S
(prOks = Odd) |
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eukaryotes vs prokaryotes
(simple mnemonic) |
- U are Eukaryote
- Pro has No nucleus |
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movement through sites during protein synth
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"APE"
site A → site P → site E A = incoming Aminoacyl tRNA P = growing Peptide E = Exits |
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where are ribosomes synth'd?
|
in the nucleus
(transported out to cytoplasm) |
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4 types of antibiotics that act as protein synthesis inhibitors
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1) AG's
2) chloramphenicol 3) macrolides 4) clindamycin |
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inhibit formation of the initiation complex & cause misreading of mRNA (in protein synthesis)
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aminoglycosides
(inhibit 30S) |
|
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inhibits 50S peptidyltransferase
(protein synth) |
chloramphenicol
(also, streptogramins) |
|
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bind 50S & blocks translocation
(protein synth) |
- macrolides
- clindamycin - (& lanezolid) |
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in the 23S RNA of the 50S subunit (of bacteria)
|
peptidyltransferase
(involved in protein synth) |
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"trimming" refers to:
|
removal of N/C terminal peptides from zymogens to generate mature proteins
(posttranslational modification) |
|
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covalent posttranslational alterations
|
- phosphorylation
- glycosylation - hydroxylation |
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3 mechanisms of proteolysis:
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1) proteasomal degrad by tagging w/UBUQUITIN
2) degrad in lysosomes 3) Ca2+-dept enzyme mech. |
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cell cycle is regulated by...
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1) CDK's (cyclin-dept kinases)
2) cyclins (activate CDK's) 3) cyclin-CDK complexes 4) tumor suppressors (Rb, p53) |
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all cyclins are degraded by what?
|
UBIQUITIN PROTEIN LIGASE!
|
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controls activation of p21
|
p53
|
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p21, p27, p57 → bind to ?
|
inativated cyclin-CDK complex
|
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Rb gene mut results it ?
|
Rb normally (-) G1-to-S progression...
mut = unrestrained growth l/t: - retinoblastoma - osteosarcoma |
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stable cells enter ___ when stimulated
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G1
(from G0) |
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labile cells
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- never go to G0
- divide rapidly - short G1 - most susceptible to cancer drugs |
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examples of labile cells:
|
- bone marrow
- gut - epithelium - skin - hair follicles |
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Rb & p53 control what?
|
what goes into S phase
|
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components needed for progression thru S phase:
|
- cyclin E
- DNA polymerase - thymidine kinase - dihydrofolate reductase |
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RER in neurons
|
nissl bodies
(synth enzymes / NT's) (in DENDRITES, NOT axons!) |
|
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site of synthesis of cytosolic & organellar proteins
|
free ribosomes
|
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site of steroid synthesis
|
smooth endoplasmic reticulum (SER)
(steroid horm-producing cells of the adrenal cortex are rich in SER) |
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site of detoxification of drugs / poisons
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smooth endoplasmic reticulum (SER)
(liver hepatocytes are rich in SER) |
|
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retrograde vesicular trafficking protein
|
COPI
(Golgi→ ER) |
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anterograde vesicular trafficking protein
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COPII
(RER→ cis-golgi) |
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clathrin
|
- "coats stuff"
- vesicular trafficking protein of golgi apparatus - trans-golgi → lysosomes, plasma memb → endosomes - (receptor mediated endocytosis) |
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disease when the golgi fails to add mannose-6-phosphate to specific lysosomal proteins (to target the protein to the lysosome)
|
I-cell disease
(inclusion cell; inherited lysosomal storage dz; enzymes are excreted OUTSIDE the cell instead of being targeted to the lysosome!) |
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I-cell clinical picture
|
- coarse facial features
- clouded corneas - restricted joint mvmt - high plasma lvls of lysosomal enzymes - often fatal in childhood (looks like Hurlers/Hunters/Skeies?) |
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microtubule proteins
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dynein & kinesin
|
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drugs that act on microtubules:
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1) bendazoles (antihelminthic)
2) griseofulvin (antifungal) 3) vincristine/vinblastine (anti-cancer; blocks polymerization) 4) paclitaxel (anti-breast cancer; makes hyperstable so cells can't divide) 5) colchicine (anti-gout) |
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microtubule polymerization defect resulting in ↓ phagocytosis
|
Chediak-Higashi syndrome
|
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Chediak-Higashi syndrome defect
|
microtubule polymerization defect resulting in ↓ phagocytosis
|
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recurrent pyogenic infections, partial albinism, & peripheral neuropathy
|
Chediak-Higashi syndrome
|
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Kartagener's syndrome defect
|
immotile cilia d/t dynein arm defect
(aka primary ciliary dyskinesia) |
|
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what accounts for the coordinated contraction of ciliar cells?
|
gap junctions
|
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intermediate filaments (cytoskeletal elements) are in:
|
- Vimentin (CT, fibroblasts)
- Desmin (musc cells) - Cytokeratin (epith cells) - Glial fibrillary acid proteins (GFAP; astrocytes, schwann cells, neuroglia) - Neurofilaments - nuclear lamins A, B, C |
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|
vimentin stains:
|
CT
(sarcomas) |
|
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desmin stains:
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muscle
(rhabdo/leio-myosarcomas) |
|
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cytokeratin stains:
|
epithelial cells
(CA's) |
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GFAP stains:
|
neuroglia
|
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neurofilaments stain:
|
neurons
(adrenal neuroblastoma, primitive neuroectoderm) |
|
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inhibits Na/K ATPase by binding to K+ site
|
Ouabain
|
|
|
directly inhibits Na/K ATPase
|
cardiac glycosides → digoxin, digitoxin
(l/t indirect (-) of Na/Ca exchange = ↑'s intracell Ca2+ = ↑'s dp/dt) |
|
|
type I collagen:
|
- bone
- skin - tendon - dentin - fascia - cornea - late wound repair |
|
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type 2 collagen:
|
- cartilage (incl hyaline)
- vitreous body - nucleus pulposus (remnant of notochord) |
|
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type 3 collagen:
|
(reticulin)
- skin - blood vessels - uterus - fetal tissue - granulation tissue (early wound healing) |
|
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type 4 collagen:
|
- basement membrane
- basal lamina ("type 4, under the floor") |
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collagen type in bone
|
type I
|
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collagen type in skin
|
type 1 & 3
|
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collagen type in tendon
|
type I
|
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collagen type in dentin
|
type I
|
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collagen type in fascia
|
type I
|
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collagen type in cornea
|
type I
|
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collagen type in late wound repair
|
type I
|
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collagen type in cartilage
|
type 2
|
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collagen type in vitreous body
|
type 2
|
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collagen type in nucleus pulposus (remnant of notochord)
|
type 2
|
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collagen type in blood vessels
|
type 3
|
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collagen type in uterus
|
type 3
|
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collagen type in fetal tissue
|
type 3
|
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collagen type in granulation tissue (early wound healing)
|
type 3
|
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collagen type in basement membrane
|
type 4
|
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collagen type in basal lamina
|
type 4
|
|
|
deposition of too much collagen
|
keloid
(use GC to (-) collagen synth) |
|
|
collagen synthesis inside the fibroblast
|
1) synthesis (RER)
2) hydroxylation (ER) (scurvy) 3) glycosylation (ER) (osteogen imperf) 4) exocytosis (5 & 6 are done outside the fibroblast) |
|
|
hydroxylation of proline & lysine residues in the 2nd step of collagen synthesis requires what?
|
vitamin C
(if you lack this→ scurvy) |
|
|
steps of collagen synthesis outside the fibroblast
|
5) proteolytic processing
6) cross-linking (ehlers-danlos) |
|
|
can't glycosylate lysine residues in collagen synth→ SO, can't make procollagen
|
osteogenesis imperfecta
(3rd step of collagen synth) |
|
|
can't cross-link tropocollagen to make collagen fibrils
|
ehlers-danlos
|
|
|
collagen type affected in ehlers danlos
|
type 3
|
|
|
collagen type affected in osteogenesis imperfecta
|
type 1
|
|
|
collagen type affected in alport's syndrome
|
type 4
|
|
|
progressive hereditary nephritis & deafness; may be a/w ocular disturbances
|
Alport's syndrome
("can't see, can't pee, can't hear"; messed up BM of kidney, ears & eyes) |
|
|
elastin
|
the stretchy protein in:
- lungs - large arteries - elastic ligaments - vocal cords - ligamenta flava (connects verts) |
|
|
elastin is rish in
|
proline & glycine
|
|
|
elastin is broken down by
|
elastase!
(inhibited by alpha1-antitrypsin) |
|
|
2 elastin diseases
|
1) marfan's (defect in fibrillin)
2) emphysema (a1-antitrypsin deficiency) |
|
|
defect in fibrillin
|
marfan's
|
|
|
southern vs. northern vs. western blots
|
"SNoW DRoP"
- South = DNA sample = DNA probe - North = RNA sample = DNA probe - West = Protein sample = antibody probe |
|
|
3 steps of PCR
|
1) denature (by heat)
2) anneal (during cooling, premade DNA primers anneal) 3) elongate (replicates DNA seq after each primer→ get 2 dsDNA) (repeat for amplification) |
|
|
what travels further in agarose gel electrophoresis?
|
smaller molecules
|
|
|
ELISA is testing for:
|
antigen-antibody reactivity
pt's blood is probed w/either test Ag (does immune syst recog?) or test Ab (is Ag present in pt?) |
|
|
uses known fluorescent DNA/RNA probe that binds to specific gene site of interest
|
fluorescence in situ hybridization (FISH)
|
|
|
used for specific localization of genes & direct visualization of anomalies (e.g. microdeletions) at the molecular level (when deletion is too small to see w/karyotype)
|
fluorescence in situ hybridization (FISH)
|
|
|
knock-out
|
removing a gene
|
|
|
knock-in
|
inserting a gene
|
|
|
aerobic metabolism of glucose produces __ ATP via ___
|
- 32 ATP via malate-aspartate shuttle (heart & liver)
- 30 ATP via glycerol-3-phosphate shuttle (muscle) |
|
|
anaerobic glycolysis produces __ ATP per glucose molecule
|
2 net ATP/glucose
|
|
|
can be coupled to energetically unfavorable rxns
|
ATP hydrolysis
|
|
|
activated carriers: phosphoryl
|
uses ATP
|
|
|
activated carriers: electrons
|
uses NADH, NADPH, FADH2
|
|
|
activated carriers: acyl
|
uses coenzyme A, lipoamide
|
|
|
activated carriers: CO2
|
uses biotin
|
|
|
activated carriers: 1-carbon units
|
uses tetrahydrofolate
|
|
|
activated carriers: CH3 groups
|
use SAM (S-adenosyl-methionine)
|
|
|
activated carriers: aldehydes
|
use TTP (thiamine pyrophosphate)
|
|
|
NADPH is a product of ?
|
the HMP shunt
|
|
|
functions of NAD+ & NADPH
|
- NAD+ = used in CATABOLIC processes to carry reducing equivs away as NADH (to go make energy w/it)
- NADPH = ANABOLIC processes (steroid & FA synth) as supply of reducing equivs (hint: cat takes things apart...& anaerobic puts 'em together--anabolic steroids build you up) |
|
|
4 processes that use NADPH
|
1) anabolic processes
2) respiratory burst 3) P-450 4) glutathione reductase |
|
|
the 1st step of glycolysis
|
- phosphorylation of glucose to glucose-6-phosphate
- catalyzed by either hexokinse or glucokinase (keep glucose inside cell!) |
|
|
hexokinase vs. glucokinase -- location
|
- hexo = it's everywhere
- gluco = in liver & beta cells of panc |
|
|
hexokinase vs. glucokinase -- affinity & capacity
|
HEXO:
- high affinity (low Km) - low capacity (low Vmax) GLUCO: - low affinity (high Km) - high capacity (high Vmax) |
|
|
insulin effects on hexokinase
|
uninduced by insulin
|
|
|
insulin effects on glucokinase
|
induced by insulin
(can control it w/insulin) |
|
|
is hexokinase or glucokinase feedback inhibited by glucose-6-phosphate?
|
hexokinase
|
|
|
phosphorylates excess glucose (e.g. after a meal) to sequester it in the liver; allows liver to serve as blood glucose "buffer"
|
glucokinase
|
|
|
hexokinase/glucokinase catalyzes...
|
glucose → glucose-6-phosphate
(reqs ATP) |
|
|
phosphofructokinase-1 catalyzes...
|
fructose-6-P→fructose-1,6-BP
(reqs ATP) |
|
|
inhibits phosphofructokinase-1
|
ATP & citrate
(↑ citrate = TCA cycle backed up!) (↑ ATP = you have enough energy!) |
|
|
stims phosphofructokinase-1
|
AMP & fructose-2,6-BP
(↑ AMP = you used all your energy & need more!) (↑ fructose-2,6-BP = your fed & can now make more energy) |
|
|
inhibits hexokinase/glucokinase
|
↑ glucose-6-P (neg feedback)
|
|
|
pyruvate kinase catalyzes...
|
phosphoenolpyruvate → pyruvate
(makes ATP) |
|
|
inhibits pyruvate kinase
|
ATP & alanine
(↑ ATP = neg fb, don't need to make more...) |
|
|
pyruvate dehydrogenase catalyzes...
|
pyruvate → acetyl-CoA
(get energy out!) |
|
|
inhibits pyruvate dehydrogenase
|
ATP, NADH & acetyl-CoA
(if ↑ NADH = it's backed up/saturated system) |
|
|
what happens to glucagon in FASTING state?
|
↑ glucagon→ ↑ cAMP → ↑ protein kinase A → ↑FBPase-2 & ↓PFK-2
(↑ glucagon b/c you want to get energy from reserves...F-2,6-bisphos is storing energy & FBase-2 releases it by changing it back to fructose-6-P that can go on to glycolysis) |
|
|
what happens to glucagon in the FED state?
|
↑ insulin → ↓ cAMP → ↓ protein kinase A → ↓FBPase-2 & ↑PFK-2
(PFK-2 turns fructose-6-P into fructose-2,6-P to "store" energy) |
|
|
RBC's metabolize glucose [aerobically / anaerobically]?
|
anaerobically
(no mitochondria; depend solely on glycolysis!) |
|
|
glycolytic enzyme deficiency is a/w...
|
hemolytic anemia → RBC's can't maintain Na-K ATPase activity & l/t swelling & lysis
(b/c RBC's NEED glycolysis to maintain this pump & if they are missing glycolysis enzymes, they can't do it) (95% d/t deficiencies in pyruvate kinase; 4% d/t phosphoglucose isomerase) |
|
|
most glycolytic enzymes deficiencies are d/t...
|
pyruvate kinase
(phosphoenolpyruvate→pyruvate) (95%... 4% are d/t phosphoglucose isomerase) |
|
|
5 coenzymes required for pyruvate dehydrogenase complex
|
"Tender Loving Care For Noone"
- pyrophosphate (B1/Thiamine; TPP) - Lipoic acid - CoA (B5/pantothenate) - FAD (B2/riboflavin) - NAD (B3/niacin) |
|
|
Activated by exercise
|
pyruvate dehydrogenase complex!
↑ NAD+/NADH ratio ↑ ADP ↑ Ca2+ |
|
|
pyruvate dehydrogenase complex reaction
|
pyruvate* + NAD+ + CoA → acetyl-CoA* + CO2 + NADH
(takes pyruvate from glycolysis & turns it into acetyl-CoA to go into TCA cycle!) |
|
|
inhibits lipoic acid
|
arsenic
|
|
|
vomiting, rice water stools, garlic breath
|
arsenic poisoning
|
|
|
causes backup of substrate (pyruvate & alanine) resulting in lactic acidosis
|
pyruvate dehydrogenase deficiency
|
|
|
is pyruvate dehydrogenase deficiency congenital or acquired?
|
both!
congenital or seen w/alcoholics (d/t B1 deficiency) |
|
|
pyruvate dehydrogenase deficiency sxs
|
neurologic defects
|
|
|
tx for pyruvate dehydrogenase deficiency
|
↑ intake of ketogenic nutrients
(high fat content or ↑ lysine & leucine - the only purely ketogenic AAs) |
|
|
4 different metabolite products of pyruvate
|
1) alanine (carries amino groups from liver to musc; ALT)
2) Oxaloacetate (replenish TCA cycle; used in gluconeogenesis) 3) Acetyl-coA (transition from glycolysis to TCA) 4) Lactate (end of anaerobic glycolysis) |
|
|
anaerobic glycolysis is a major pathway in...
|
1) RBCs
2) leukocytes 3) kidney medulla 4) testes 5) lens & cornea |
|
|
function of the Cori Cycle
|
allows lactate generated in anaerob. metab to undergo hepatic gluconeogen & become source of glucose for musc/RBCs
(shifts metabolic burden to the liver--RBCs dont have much energy to spare..) (recycles lactate) |
|
|
1st step of TCA cycle
|
acetyl-CoA + OAA →[citrate synthase]→ citrate
(enzyme is irreversible) |
|
|
2nd step of TCA cycle
|
citrate → isocitrate →[isocitrate DH]→ alpha-ketoglutarate
(enzyme is rirreversible) |
|
|
3rd step of TCA cycle
|
a-KG →[a-KG DH]→ Succinyl-CoA
(enzyme is irreversible) |
|
|
cofactors of a-KG DH complex
|
B1, B2, B3, B5, lipoic acid
"Tender Loving Care For Noone" - Thiamine (B1, pyrophosphate/TPP) - Lipoic acid - CoA (B5/pantothenate) - FAD (B2/riboflavin) - NAD (B3/Niacin) |
|
|
function of electron transport chain
|
pumps H+ into cell → to make gradient (w/energy from NADH)
|
|
|
what complexes in the electron transport chain pump H+?
|
complex I, III, & IV
(complex V uses the created H+ gradient to turn & create energy/ATP) |
|
|
aka Complex V
|
ATP synthase
(releases energy) |
|
|
1 NADH makes __ ATP via ATP synthase.
|
3 ATP
|
|
|
1 FADH2 makes __ ATP via ATP synthase.
|
2 ATP
|
|
|
electron transport inhibitors
|
- rotenone (complex 1)
- CN- (complex 4) - antimycin A (complex 3) - CO (complex 4) |
|
|
MOA of electron transport inhibitors
|
directly (-) electron transport causing ↓ proton gradient & block of ATP synthesis
(they each block a specific complex in the chain) |
|
|
ATPase inhibitors
|
oligomycin
|
|
|
MOA of ATPase inhibitors
|
directly (-) mitochon. ATPase, causing ↑ proton gradient→ no ATP produced b/c electron transport stops
|
|
|
3 types of oxidative phosphorylation poisons
|
1) electron transport inhibitors
2) ATPase inhibitors 3) uncoupling agents |
|
|
MOA of uncoupling agents
|
↑ permeability of memb→ causing ↓ proton gradient & ↑ O2 consumption→ ATP synth stops but elec transport continues→ produces heat/hyperthermia (instead of ATP! not an efficient use of energy...)
(basically makes a 2nd hole) |
|
|
uncoupling agents
|
- 2,4-DNP (wood preservation agent)
- aspirin (fevers occur w/OD) - thermogenin in brown fat (hibernating animals) |
|
|
gluconeogenesis irreversible enzymes
|
1) Pyruvate carboxylase
2) PEP carboxykinase 3) Fructose-1,6-bisphosphatase 4) Glucose-6-phosphatase ("Pathway Produces Fresh Glucose") |
|
|
where is pyruvate carboxylase?
|
in mitochondria (primarily in liver)
(gluconeogenesis: pyruvate → OAA) |
|
|
where is PEP carboxykinase?
|
in cytosol (primarily in liver)
(gluconeogenesis: OAA→ phosphoenolpyruvate) |
|
|
where is fructose-1,6-bisphosphatase?
|
in cytosol (primarily in liver)
(gluconeogenesis: fructose-1,6-bisphosphate→fructose-6-P) |
|
|
where is glucose-6-phosphatase?
|
in ER (primarily in liver)
(gluconeogenesis: glucose-6-P→glucose) |
|
|
pyruvate carboxylase conversion of pyruvate→OAA requires:
|
biotin & ATP
(& activated by acetyl-CoA) (takes energy b/c you're MAKING glucose) |
|
|
pyruvate carboxylase conversion of pyruvate→OAA is activated by:
|
acetyl-CoA
|
|
|
PEP carboxykinase conversion of OAA→phosphoenolpyruvate requires:
|
GTP
(takes energy b/c you're MAKING glucose) |
|
|
gluconeogenesis takes place in:
|
- primarily in liver
- also in kidney - also in intestinal epithelium |
|
|
deficiency of key gluconeogenic enzymes causes ____.
|
hypoglycemia
(enzs: Pyruvate carboxylase, PEP carboxykinase, Fructose-1,6-bisphosphatase, Glucose-6-phosphatase) |
|
|
why can't muscle participate in gluconeogenesis?
|
b/c it lacks glucose-6-phosphatase, one of the key enzymes...
|
|
|
how can odd-chain fatty acids serve as a glucose source?
|
they yield 1 propionyl-CoA during metabolism→ can enter TCA cycle (as succinyl-CoA) & undergo gluconeogen
|
|
|
function of HMP shunt (aka pentose phosphate pathway)
|
- makes NADPH from glucose-6-phosphate!
- NADPH = req for reductive rxns (like glutathione reduction in RBCs) - yields ribose for nucleotide synth & glycolytic intermeds |
|
|
cellular location of HMP shunt
|
cytoplasm
|
|
|
energy required for HMP shunt
|
no ATP used or produced
(energy neutral..) |
|
|
location(s) of HMP shunt
|
- lactating mammary glands
- liver - adrenal cortex (sites of FA or steroid synth) - RBCs |
|
|
phases of HMP shunt
|
1) oxidative (irreversible)
2) nonoxidative (reversible) |
|
|
key enzyme of HMP shunt oxidative reaction
|
Glucose-6-P dehydrogenase (RLS)
(glucose-6-Pi→CO2 + 2NADPH + Ribulose-5-Pi) (irreversible) |
|
|
key enzyme of HMP shunt nonoxidative reaction
|
Transketolases
(Ribulose-5-Pi→Ribulose-6-Pi + G3P + F6P) (reversible) |
|
|
NADPH oxidation→
|
reduces things (gives them H+)
(LEO goes GER) |
|
|
respiratory burst function(s)
|
- uses NADPH oxidase (in PMNs, macs)
- plays role in immune response - results in rapid release of reactive oxygen intermediates (reduces oxygen→making it really reactive→stores up for killing shit) |
|
|
NADPH oxidase deficiency
|
chronic granulomatous disease
|
|
|
chronic granulomatous dz is susceptible to what kind of infection?
|
catalase-(+) b/c they neutralize their own H2O2
(S. aureus, Aspergillus...) |
|
|
↓ NADPH in RBCs l/t:
|
hemolytic anemia
(b/c RBCs can't defend against oxidizing agents w/o NADPH which is req to keep glutathione reduced which in turn detoxifies free radicals & peroxides → G6PD deficiency) |
|
|
oxidizing agents
|
- fava beans
- sulfonamides - primaquine - TB drugs |
|
|
why is G6PD deficiency bad?
|
can't make NADPH→ can't reduce glutathione → cant protect against free radicals & peroxides → hemolytic anemia (in response to oxidizing agents)
|
|
|
MC human enzyme deficiency
|
G6PD deficiency
|
|
|
G6PD inheritance
|
XLR
|
|
|
what is a Heinz body?
|
oxidized Hgb precipitated w/in RBCs
(see in G6PD deficiency) |
|
|
what do bite cells result from?
|
phagocytic removal of Heinz bodies by macrophages
(see in G6PD deficiency) |
|
|
deficiency of aldolase B
|
fructose intolerance!
|
|
|
accumulates w/fructose intolerance
|
fructose-1-phosphate
(causes ↓ in available phosphate→ inhibs glycogenolysis & gluconeogenesis!) |
|
|
hypoglycemia, jaundice, cirrhosis, vomiting (hereditary)
|
fructose intolerance
|
|
|
tx for fructose intolerance
|
↓ intake of fructose & sucrose (glucose+fructose)
|
|
|
defect in fructokinase
|
essential fructosuria
(benign) |
|
|
fructose in blood & urine
|
essential fructosuria
(benign) |
|
|
enzyme defect of essential fructosuria
|
fructokinase
|
|
|
enzyme a/w fructose intolerance
|
deficiency of aldolase B
|
|
|
absence of galactose-1-phosphate uridyltransferase
|
classic galactosemia
|
|
|
enzyme a/w classic galactosemia
|
absent galactose-1-phosphate uridyltransferase
|
|
|
failure to thrive, jaundice, hepatomegaly, infantile cataracts, MR
|
classic galactosemia
|
|
|
mechanism of damage of classic galactosemia
|
accum of toxic substances
(incl galactitol, which accums in lens of eye→ infantile cataracts) |
|
|
tx for classic galactosemia
|
exclude galactose & lactose (galactose+glucose) from diet
|
|
|
hereditary deficiency of galactokinase
|
galactokinase deficiency
(mild condition) |
|
|
what accums w/galactokinase deficiency?
|
galactitol
(relatively mild condition) |
|
|
galactose in blood & urine
|
galactokinase deficiency
(can have infantile cataracts) |
|
|
infantile cataracts
|
classic galactosemia or galactokinase deficiency
|
|
|
may initially present as failure to track objects or to develop a social smile
|
galactokinase deficiency
|
|
|
alternative method of trapping glucose in the cell
|
convert it to its alcohol counterpart→ sorbitol (via aldose reductase)
|
|
|
some tissues convert sorbitol to fructose using:
|
sorbitol dehydrogenase
|
|
|
tissues that have both aldose reductase & sorbitol dehydrogenase
|
- liver
- ovaries - seminal vesicles |
|
|
tissues that only have aldose reductase (& no sorbitol dehydrogenase)
|
- Schwann cells
- lens - retina - kidneys (in danger of sorbitol accum!! → ↑H2O = cell swell = damage!) |
|
|
what leads to sorbitol accumulation?
|
prolonged hyperglycemic states
(e.g. diabetes! → damage causes cataracts, retinopathy, & peripheral neuropathy) |
|
|
what pathway is responsible for cataracts, retinopathy, and peripheral neuropathy of diabetics?
|
prolonged hyperglycemic state→ ↑glucose → converted to sorbitol by ALDOSE REDUCTASE!
sorbitol damages eyes, nerves & kidneys b/c it cant be broken down to fructose in those organs.. (b/c no sorbitol dehydrogenase) |
|
|
lactase deficiency is d/t loss of what?
|
brush-border enzyme
(can follow gastroenteritis) |
|
|
bloating, cramps, osmotic diarrhea
|
lactase deficiency
|
|
|
rate limiting step of urea cycle
|
carbamoyl phosphate synthetase I (CPS1)
(CO2 + NH4+ → carbamoyl phosphate) |
|
|
enzyme that enters carbamoyl phosphate into the urea cycle
|
ornithine transcarbamoylase
|
|
|
how is excess nitrogen (NH4+) generated from formation of common metabolites (like pyruvate, acetyl-CoA) gotten rid of?
|
enters urea cycle→ NH4+ converted to urea → excreted in urine
|
|
|
urea is composed of:
|
NH4+ + CO2 + aspartate
|
|
|
sxs of ammonia intoxication
|
- tremor (asterixis/hand flapping)
- slurring speech - somnolence - vomiting - cerebral edema - blurring of vision |
|
|
cause of hyperammonemia
|
acquired = d/t liver disease
hereditary = d/t urea cycle enzyme deficiency |
|
|
mechanism of hyperammonemia damage
|
excess NH4+ depletes a-KG→ l/t (-) of TCA cycle
|
|
|
tx for hyperammonemia d/t enzyme deficiency
|
benzoate or phenylbutyrate
(bind to AA & l/t excretion) |
|
|
tx of hyperammonemia d/t liver disease
|
lactulose
(ammonia trapped in gut & excr) |
|
|
MC urea cycle d/o
|
ornithine transcarbamoylase (OTC) deficiency
|
|
|
orotic acid in blood & urine
|
ornithine transcarbamoylase deficiency
(cant get rid of urea in urea cycle) |
|
|
↓BUN & sxs of hyperammonemia
|
ornithine transcarbamoylase deficiency
(can't get rid of urea in urea cycle) |
|
|
excess carbamoyl phosphate → converted to orotic acid
|
ornithine transcarbamolase deficiency
(cant get rid of urea in urea cycle) |
|
|
the only XLR urea cycle enzyme deficiency
|
ornithine transcarbamoylase deficiency
(vs others that are AR) |
|
|
derivatives of phenylalanine
|
phenylalanine→ tyrosine→ dopa→ DA→ NE→ Epi
tyrosine→ thyroxine dopa→ melanin |
|
|
derivatives of tryptophan
|
(w/B6 cofactor)→ B3/niacin→ NAD+/NADP+
→ serotonin→ melatonin |
|
|
derivatives of histadine
|
(w/B6 cofactor)→ histamine
|
|
|
derivatives of glycine
|
(w/B6 cofactor)→ porphyrin→ heme
|
|
|
derivatives of arginine
|
→ creatine
→ urea → nitric oxide |
|
|
derivates of glutamine
|
(w/B6 cofactor)→ GABA (glutamate decarboxylase--reqs B6)
→ glutathione |
|
|
enzyme that catalyzes:
phenylalanine→tyrosine |
phenylalanine hydroxylase
|
|
|
phenylalanine hydroxylase deficiency causes...
|
PKU
|
|
|
enzyme that catalyzes:
tyrosine→dihydroxyphenylalanine (aka "dopa") |
tyrosine hydroxylase
|
|
|
enzyme that catalyzes:
dopa (dihydroxyphenylalanine)→dopamine |
dopa decarboxylase
(requires B6) |
|
|
what enzyme does carbidopa inhibit?
|
dopa decarboxylase
|
|
|
enzyme that catalyzes:
DA→Norepi |
dopamine beta-hydroxylase
(requires vitamin C) |
|
|
breakdown product(s) of dopamine (via MAO & COMT)
|
HVA
|
|
|
breakdown product(s) of norepinephrine (via MAO & COMT)
|
VMA
|
|
|
breakdown product(s) of epinephrine(via MAO & COMT)
|
metanephrine
|
|
|
d/t ↓ phenylalanine hydroxylase
|
phenylketonuria (PKU)
(or can be d/t ↓ tetrahydrobiopterin cofactor) |
|
|
d/t ↓ tetrahydrobiopterin cofactor
|
PKU
(or can be d/t ↓ phenylalanine hydroxylase) |
|
|
MR, growth retardation, seizures, fair skin, eczema, musty body odor
|
PKU
|
|
|
tx of PKU
|
↓ phenylalanine (contained in aspartame) & ↑ tyrosine in diet
|
|
|
infant w/ microcephaly, MR, growth retardation, congenital heart defects
|
maternal PKU
(mom w/untx PKU) |
|
|
excess phenylketones in urine
|
PKU
|
|
|
tyrosine becomes essential
|
in PKU (d/t ↓ phenylalanine hydroxylase or tetrahydrobiopterin cofactor)
|
|
|
disease screened for 2-3 days after birth because it is so important to dx & tx w/in 1st 3 wks of life to prevent irreversible sxs
|
PKU
|
|
|
phenylketones
|
- phenylacetate
- phenyllactate - phenylpyruvate |
|
|
d/o of aromatic AA metabolism
|
PKU
(must body odor) |
|
|
deficiency of homogentisic acid oxidase
|
alkaptonuria
(ochronosis) |
|
|
urine turns black on standing
|
alkaptonuria
(benign) |
|
|
dark CT, pigmented sclera, may have debilitating arthralgias
|
alkaptonuria
(benign besides the arthralgias) |
|
|
enzyme a/w alkaptonuria
|
congenital deficiency of homogentisic acid oxidase
(in degradative pathway of tyrosine) |
|
|
deficiencies that lead to albinism
|
1) tyrosinase (can't synth melanin from tyrosine)
2) defective tyrosine transporters (can also be from lack of migration of neural crest cells) |
|
|
albinism (d/t tyrosinase deficiency) inheritance
|
variable inheritance d/t locus heterogeneity (AR)
(v. ocular albinism = XLR) |
|
|
deficiencies a/w homocystinuria
|
1) cystathionine synthase deficiency
2) homocysteine methyltransferase deficiency |
|
|
non-deficiency cause of homocystinuria
|
↓ affinity of cystathionine synthase for pyridoxal phosphate
|
|
|
excess homocysteine
|
homocystinuria
|
|
|
cysteine becomes essential
|
homocystinuria
|
|
|
↑↑ homocysteine in urine, MR, osteoporosis, tall stature, kyphosis, lens subluxation (down & in), & atherosclerosis (stroke, MI)
|
homocystinuria
|
|
|
tx for cystathionine synthase deficiency (homocystinuria)
|
↓ Met, ↑ Cys, ↑B12 & folate
|
|
|
tx for ↓ affinity of cystathionine synthase for pyridoxal phosphate (homocystinuria)
|
↑↑ vitamin B6 in diet
|
|
|
hereditary defect of renal tubular AA transport for cysteine, ornithine, lysine & arginine in the PCT of the kidneys
|
cystinuria
|
|
|
cystinuria
|
AR hereditary defect of renal tubular AA transport for cysteine, ornithine, lysine & arginine in the PCT of the kidneys
|
|
|
cystinuria can lead to what renal problem
|
excess cysteine in urine can lead to precipitation of cystine kidney stones (staghorn calculi)
|
|
|
what can lead to staghorn calculi
|
cystinuria
|
|
|
tx of cystinuria
|
acetazolamide (to alkalinize urine)
|
|
|
blocked degradation of branched AA's (Ile, Leu, Val)
|
maple syrup urine disease
(I Love Vermont maple syrup from trees w/branches = Ile, Leu, Val) |
|
|
maple syrup urine disease is d/t...
|
blocked degradation of branched AA's (Ile, Leu, Val) d/t ↓ alpha-ketoacid dehydrogenase
(I Love Vermont maple syrup from trees w/branches = Ile, Leu, Val) |
|
|
causes ↑ a-ketoacids in blood, esp Leu
|
maple syrup urine dz
|
|
|
hartnup disease
|
AR d/o of defective neutral AA transporter on renal & intestinal epithelial cells
(leads to pellagra--d/t niacin deficiency) |
|
|
defective neutral AA transporter on renal & intestinal epithelial cells
|
hartnup disease
|
|
|
causes tryptophan excretion in urine & absorption from the gut
|
hartnup disease
|
|
|
glycogen branches have alpha(??) bonds
|
a(1,6)
|
|
|
glycogen linkages have alpha(??) bonds
|
a(1,4)
|
|
|
in muscle, glycogen undergoes ___
|
glycogenolysis (to form glucose)
|
|
|
in hepatocytes, glycogen is..?
|
stored & undergoes glycogenolysis to maintain blood sugar @ appropriate levels
|
|
|
what is rapidly metabolized in the skeletal muscle during exercise
|
glucose
|
|
|
deficient enzyme in von Gierke's (type I)
|
glucose-6-phosphatase
|
|
|
deficient enzyme in Pompe's (type II)
|
lysosomal a-1,4-glucosidase (acid maltase)
|
|
|
deficient enzyme in Cori's dz (type III)
|
debranching enzyme (a-1,6-glucosidase)
|
|
|
deficient enzyme in McArdle's dz (type V)
|
skeletal muscle glycogen phosphorylase
|
|
|
glycogen storage diseases
|
1) von Gierke's (type I)
2) Pompe's (type II) 3) Cori's (type III) 4) McArdle's (type V) |
|
|
cardiomegaly & systemic findings, l/t early death (by 3 yrs)
|
Pompe's dz
|
|
|
milder form of type I / von Gierke's
|
Cori's disease (type III)
(normal blood lactate levels) |
|
|
findings of von Gierke's disease
|
- severe fasting hypoglycemia
- ↑ glycogen in liver - ↑ blood lactate (anaerobic metab) - hepatomegaly |
|
|
↑ glycogen in muscle, but can't break it down→ l/t painful muscle cramps & myoglobinuria w/exercise
|
McArdle's
(but longevity not affected) |
|
|
deficient a-galactosidase A
|
Fabry's disease
|
|
|
deficient b-glucocerebrosidase
|
Gaucher's dz
|
|
|
MC lysosomal storage disease
|
Gaucher's dz
|
|
|
deficient sphingomyelinase
|
Niemann-Pick disease
|
|
|
deficient hexosaminidase A
|
Tay-Sachs disease
|
|
|
deficient galactocerebrosidase
|
Krabbe's disease
|
|
|
deficient Arylsulfatase A
|
metachromatic leukodystrophy
|
|
|
deficient a-L-iduronidase
|
Hurler's syndrome
|
|
|
deficient Iduronate sulfatase
|
Hunter's syndrome
|
|
|
the only 2 XLR lysosomal storage diseases
|
(1) Fabry's
(2) Hunter's syndrome (X marks the spot for a treasure Hunter) (the rest are AR) |
|
|
substrate accumulated in fabry's
|
ceramide trihexoside
|
|
|
substrate accumulated in Gaucher's
|
glucocerebroside
|
|
|
substrate accumulated in Niemann-Pick
|
sphingomyelin
|
|
|
substrate accumulated in Tay-Sachs
|
GM2 ganglioside
|
|
|
substrate accumulated in Krabbe's disease
|
galactocerebroside
|
|
|
substrate accumulated in metachromatic leykodystrophy
|
cerebroside sulfate
|
|
|
substrate accumulated in Hurler's syndrome
|
heparan sulfate, dermatan sulfate
|
|
|
substrate accumulated in Hunter's syndrome
|
Heparan sulfate, dermatan sulfate
|
|
|
lysosomal storage diseases in Ashkenazi Jews
|
- Tay-Sachs
- Niemann-Pick - some forms of Gaucher's |
|
|
inability to transport LCFAs into the mitochondria, resulting in toxic accumulation
|
carnitine deficiency
|
|
|
weakness, hypotonia, and hypoketotic hypoglycemia
|
carnitine deficiency
|
|
|
where does fatty acid degradation occur
|
where its products will be consumed--in the mitochondrion
|
|
|
RLS of fatty acid degradation
|
carnitine acyl transferase
(carnitine shuttle ??) |
|
|
Acyl-CoA dehydrogenase deficiency does what
|
↑ dicarboxylic acids
↓ glucose & ketones |
|
|
breath smells like acetone
|
ketone bodies (fruity)
|
|
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in the liver, fatty acids & AAs are metabolized to ___ & ____
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acetoacetate & beta-hydroxybutyrate (to be used in muscle & brain)
|
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what things cause the shunting of glucose & FFAs toward the production of ketone bodies (by stalling TCA cycle)?
|
1) prolonged starvation (OAA is depleted for gluconeogenesis)
2) DKA (same as 1) 3) alcoholism (excess NADH shunts OAA to malate) |
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|
ketones are made from ___
|
HMG-CoA
|
|
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ketones are metabolized by the brain to ___
|
2 molecules of acetyl-CoA
|
|
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ketones are excreted in ...
|
urine
|
|
|
what class of drugs inhibit HMG-CoA reductase?
|
statins
(RLS of cholest synth) |
|
|
statins inhibit..?
|
HMG-CoA reductase
(RLS of cholesterol synth) |
|
|
1 g protein = ? kcal
|
4 kcal
(same as carbs) |
|
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1 g carbohydrate = ? kcal
|
4 kcal
(same as protein) |
|
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1 g fat = ? kcal
|
9 kcal
|
|
|
ATP is obtained from where during a 100 meter sprint (seconds)?
|
- stored ATP
- creatine phosphate - anaerobic glycolysis |
|
|
ATP is obtained from where during a 1000 meter run (minutes)?
|
- stored ATP
- creatine phosphate - anaerobic glycolysis - oxidative phosphorylation |
|
|
ATP is obtained from where during a marathon (hours)?
|
- glycogen & FFA oxidation
- glucose conserved for final sprinting |
|
|
during days 1-3 of fasting/starvation, blood glucose is maintained by:
|
1) hep glycogenolysis & glucose release
2) adipose release of FFA 3) musc & liver shifting fuel use from glucose to FFA 4) hep gluconeogenesis from periph tissue lactate & alanine, and from adipose tissue glycerol & propionyl-CoA from odd-chain FFA metab |
|
|
after day 3 of fasting/starvation
|
musc protein loss → maintained by hepatic formation of ketone bodies → supplies brain & heart
|
|
|
main source of energy for brain after several weeks of fasting/starvation
|
ketone bodies (so ↓ musc protein loss)
|
|
|
catalyzes esterification of cholesterol
|
Lecithin-cholesterol acyltransferase (LCAT)
(puts cholest on HDL particles) |
|
|
mediates transfer of cholesterol esters to other lipoprotein particles
|
cholesterol ester transfer protein (CETP)
(allows HDL to deposit cholest on LDL, VLDL...) |
|
|
degrades dietary TG in small intestine
|
pancreatic lipase
|
|
|
degrades TG circulating in chylomicrons & VLDLs
|
lipoprotein lipase (LPL)
|
|
|
degrades TG remaining in IDL
|
hepatic TG lipase (HL)
|
|
|
degrades TG stored in adipocytes
|
hormone-sensitive lipase
|
|
|
5 major apolipoproteins
|
1) A-I
2) B-100 3) C-II 4) B-48 5) E |
|
|
activates LCAT
|
apolipoprotein A-I
|
|
|
binds to LDL receptor, mediates VLDL secretion
|
apolipoprotein B-100
|
|
|
Cofactor for lipoprotein lipase
|
apolipoprotein C-II
|
|
|
C3 inhibits --?
|
lipoprotein lipase
|
|
|
mediates chylomicron secretion
|
apolipoprotein B-48
|
|
|
mediates Extra (remnant) uptake
|
apolipoprotein E
|
|
|
apolipoprotein A-I
|
Activates LCAT
|
|
|
apolipoprotein B-100
|
- Binds to LDL receptor
- mediates VLDL secretion |
|
|
apolipoprotein C-II
|
Cofactor for lipoprotein lipase
|
|
|
apolipoprotein B-48
|
mediates chylomicron secretion
|
|
|
apolipoprotein E
|
mediates Extra (remnant) uptake
|
|
|
type I familial dyslipidemia
|
hyperchylomicronemia
|
|
|
type IIa familial dyslipidemia
|
familial hypercholesterolemia
|
|
|
type IV damilia dyslipidemia
|
hypertriglyceridemia
|
|
|
what has elevated blood levels in hyperchylomicronemia
|
TG & cholesterol
|
|
|
what has elevated blood levels in familial hypercholesterolemia
|
cholesterol
|
|
|
what has elevated blood levels in hypertriglyceridemia
|
TG
(↑'d VLDL) |
|
|
cause/pathophys of hyperchylomicronemia (type I dyslipidemia)
|
- lipoprotein lipase deficiency
- OR altered apolipoprotein C-II |
|
|
S/S of hyperchylomicronemia
|
- pancreatitis (↑TG)
- hepatosplenomegaly - eruptive/pruritic xanthomas - NO ↑ risk of atherosclerosis |
|
|
cause/pathophys of hypertriglyceridemia
|
hepatic overproduction of VLDL
(can cause pancreatitis d/t ↑TGs) |
|
|
hereditary inability to synth lipoproteins
|
Abeta-lipoproteinemia
|
|
|
why can't you synth lipoproteins in Abeta-lipoproteinemia?
|
d/t deficiencies in apoB-100 & apoB-48
|
|
|
failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness (sxs in 1st few months of life)
|
Abeta-lipoproteinemia
(acanthocytosis = spikey RBC) |
|
|
intestinal biopsy shows accum of lipid w/in enterocytes
|
Abeta-lipoproteinemia
(can't get rid of chylomicrons) |
|
|
tx for Abeta-lipoproteinemia
|
vitamin E
|
|
|
function of chylomicrons
|
- delivery dietary TGs to periph tissue
- deliver cholest to liver in form of chylomicron remnants (mostly depleted of triacylglycerols) |
|
|
chylomicrons are secreted by ?
|
intestinal epithelial cells
|
|
|
chylomicron apolipoproteins
|
- A-IV
- B-48 - C-II - E |
|
|
function of VLDL
|
delivers hepatic TGs to periph tissue
|
|
|
VLDL is secreted by ?
|
the liver
|
|
|
IDL function
|
delivers TGs & cholest to liver, where they are degraded to LDL
|
|
|
IDL is formed by...
|
degradation of VLDL
|
|
|
LDL function
|
delivers hepatic cholest to periph tissues
|
|
|
LDL is formed by...
|
lipoprotein lipase modification of VLDL in periph tissue
|
|
|
LDL is taken up by target cells via...?
|
receptor-mediated endocytosis
|
|
|
HDL function
|
- mediates reverse cholest transport from periph to liver
- acts as repository for apoC & apoE (needed for chylomicron & VLDL metab) |
|
|
HDL is secreted from:
|
liver & intestine
|
