Term
| Storage location for excess amino acids |
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Definition
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Term
| Fate of surplus amino acids |
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Definition
| urea (alpha amino) and fuel (carbon skeleton) |
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Term
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Definition
| nonspecific proteolytic enzyme of stomach |
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Term
| organs that secrete proteolytic enzymes |
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Definition
| stomach, pancreas, intestine |
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Term
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Definition
- tags protein for proteolysis
- protein must be poly-ubiqinated |
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Term
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Definition
- bond between carboxy end of Ubiquitin and ε-amino of of Lys
- invovles ATP hydrolysis |
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Term
| Enzymes that attach ubiquitin to target protein |
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Definition
- E1: ubiquitin-activating enzyme
- E2: ubiquitin conjugating enzyme
- E3: ubiquitin-protein ligase |
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Term
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Definition
Ubiquitin Activating Enzyme
1) Adenylation of carboxy end of Ub (Ub-AMP)
2) Cys on E1 displaces AMP and forcs thioester with Ub |
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Term
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Definition
Ubiquitin Conjugating Enzyme
- transfer of thioster bond from E1 to E2
- more diverse enzyme family than E1 therefore has more specific function |
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Term
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Definition
Ub-Protein Ligase
- recruits E2-S-Ub and target enzyme
- breaks thioester bond and forms isopeptide bond between Ub and Protein ε-amino of Lys
- more diverse enzyme family than E1 and E2 therefore capable of the most specific ubiquitin interactions |
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Term
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Definition
- must have at least 4 Ub-long chain to be marked for destruction
- E3 processively poly-ubiquinates |
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Term
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Definition
| amino acid sequence marking proteing for destruction |
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Term
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Definition
Degron:
- terminal amino residue determines half life
- amino terminal read by E3/Ub-protein ligase |
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Term
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Definition
Degron:
- pro-glu-ser-thr seq marking protein for destruction |
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Term
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Definition
- digests poly-ubiquinated proteins
- spits out polypeptides for further degradation by cytoplasmic peptidases
- recycles ubiquitin |
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Term
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Definition
- catalytic barrel
- α-β homologous subunits (7α-7β-7β-7α)
- β: Thr nucleophile attacks carbonyls
- β: 7 isoforms can be mixed to allow for specific targeting |
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Term
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Definition
- cover top and bottom of 20S catalytic barrel
- 6 ATPase domains
1) recognizes poly-Ub tags
2) isopeptidase: Ub recylcing
3) unfold proteins and direct to core |
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Term
| how does proteosome activity affect inflammatory reponse via NF-κB |
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Definition
- NF-κB = nuclear transcription factor inhibited by I-κB.
- inflammatory signals trigger kinases that phosphorylate IF-κB. Newly phosphorylated Ser's attract E3 |
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Term
| Parkinson Dz and Angelman Syndrome |
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Definition
- defective E3 leads to failure to degrade proteins
- neurological consequences |
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Term
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Definition
- uncontrolled protein turnover
- overactive E3 suppresses levels of p53 tumor suppressor |
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Term
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Definition
- inhibitor of a proteosome
- treatment for multiple myeloma |
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Term
| possible proteosome-based therapy for tuberculosis |
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Definition
| use HT1171 as suicide inhibitor of M. tuberculosis-specific proteosome |
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Term
| Sites of amino acid degradation |
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Definition
- mostly liver
- muscle will degrade branched-chains (VIL) |
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Term
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Definition
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Term
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Definition
- transfer α-amino from amino acid to α-ketoacid
- reversible reactions |
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Term
| Aspartate aminotransferase reaction |
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Definition
| Asp + α-Ketoglu -> OAA + Glu |
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Term
| Alanine aminotransferase reaction |
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Definition
| Ser + α-Ketoglu -> pyruvate + Glu |
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Term
| Aminotransferase coenzyme |
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Definition
pyridoxal phosphate (PLP)
- uses its reactive aldehyde to form aldimines
- Internal aldimine = bonds with enzyme's ε-amino of Lys
- External aldimine = bonds with α-amino to be transferred from amino acid
- ring acts as nucleophile/electron sink |
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Term
| Aminotransferase mechanism |
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Definition
1) α-amino displaces ε-amino
2) series of acid base reactions + hydrolysis:
AA1 + E-PLP -> α-ketoacid + E-PMP (pyridoxamine phosphate)
3) reverse reaction: after dedydration and a series of acid-base reactions, a 2nd α-ketocaid receives the amino group
α-Ketoacid2 + E-PMP -> amino acid2 + E-PLP |
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Term
| glutamate dehydrogenase location |
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Definition
| - LIVER mitochondria-specific enzyme |
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Term
| glutamate dehydrogenase purpose |
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Definition
| - convert glutamate into ammonium and regenerated α-ketoglutarate |
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Term
| glutamate dehydrogenase mechanism |
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Definition
1) reducution via NAD(P)+ to Ketimine
2) Hydrolysis of Ketimine to ammonium and regeneration α-ketoglutarate |
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Term
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Definition
Feature of Enzymes that contain PLP:
- PLP's ring structure makes any substitutent's bonds that are perpendicular to the plane of ring particularly weak
- leads to ability to deprotonate ketimine which leads to release of 2nd amino acid |
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Term
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Definition
Ser/Thr don't need Aminotransferases and can be directly deaminated
1) Dehydration
2) Deamination
- Ser-> pyruvate
- Thr->α-ketobutyrate |
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Term
| How does Muscle deliver its amino byproducts to the liver |
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Definition
Glucose-Alanine Cycle
1) In muscle, pyruvate from glycolysis combines with α-amino -> Ala
2) Ala travels to liver
3) Ala aminotransferase -> Glu + pyruvate
4a) Glu: Glutamate dehydrogenase -> α-ketoglurate + ammonium
4b) pyruvate: gluconeogenesis -> glucose |
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Term
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Definition
| organisms that excrete excess nitrogen as urea (2 N's per molecule) |
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Term
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Definition
| Liver mitochondria and cytoplasm |
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Term
| Carbamoyl Phosphate Synthetase |
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Definition
- Mitochondrial reaction
- Bicarb + NH3 + 2ATP ->
Carbamoyl Phosphate + 2 ADP + Pi
- 2 ATP's make reaction irreversible |
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Term
| Ornithine Transcarbamoylase |
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Definition
- Mitochondrial reaction
- carbamoyl phosphate + ornithine ->
Citrulline + Pi |
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Term
| Argininosuccinate Synthetase |
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Definition
- Cytoplasmic reaction
- citrulline + Asp + ATP ->
Argininosuccinate + AMP + PPi
- PPi -> 2Pi |
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Term
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Definition
- Cytoplasmic reaction
- Argininosuccinate ->
Arg + Fumarate |
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Term
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Definition
- Cytoplasmic reaction
- Arg + H2O -> ornithine + urea
- ornithine is regenerated for condensation with carbamoyl phosphate, again
- urea is excreted |
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Term
| Common intermediates between urea cycle and CAC |
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Definition
Fumarate
- Fumarate -> OAA -> glucose
- Fumarate -> OAA -> Asp (for urea cycle) |
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Term
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Definition
- blockage of carbamoyl phosphate synthetase or urea cycle
- toxic levels of ammonium
- neurological disorders |
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Term
| Argininosuccinase defficiency |
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Definition
- Can't cleave argininosuccinate to produce arg (for urea) and fumarate
- TX: give xs arginine so excreted urea carrier becomese argininosuccinate (4 nitrogens per molecule) |
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Term
| 7 Fates of carbon skeletons |
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Definition
| - pyruvate, acetoacetyl Coa, Acetyle Coa, α-ketoglutarate, succinyl Coa, fumarate, OAA |
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Term
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Definition
- only Lys and Leu are solely ketogenic
- give rise to acetyl CoA or Acetoacetyl Coa |
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Term
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Definition
- 14 amino acids solely glucogenic
- give rise to pyruvate, α-ketoglutarate, succinyl CoA, fumarate, OAA |
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Term
| Ketogenic and Glucogenic AA's |
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Definition
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Term
| Carbon skeletons that break-down to pyruvate |
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Definition
3 carbon amino acids
- Ala: Ala aminotransferase
- Ser: Ser dehydratase
- Cys |
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Term
| Carbon skeletons that breakdown to OAA |
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Definition
- Asp: Asp aminotransferase
- Arg: 1) hyrolyzed the amide to a carboxyl (asparaginase), 2) Asp aminotransferase
(pneumonic: focus on the two A's in OAA) |
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Term
| Carbon skeletons that breakddown to α-ketoglutarate |
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Definition
5 carbon amino acids
- NQPH
- 1) converted to Glu, 2) glutamate dehydrogenase |
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Term
| Carbon skeletons that breakddown to succinyl CoA |
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Definition
nonpolar amino acids
- MIV
- converted to propionyl CoA
- propionyl can enter CAC at succinl CoA: propionyl CoA Carboxylase -> methylmalonyl mutase -> succinyl CoA
(reaction first seen in the degradation of odd-chain Fatty Acids) |
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Term
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Definition
S-Adenosylmethionine
- product of Methionine degradation to succinyl CoA
- common methyl donor |
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Term
| Branched chain amino acid entry into metabolic pathway |
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Definition
Branched-Chain α-Ketoacid Dehydrogenase
- homolog of pyruvate dehydrogenase
1) transamination to α-ketoacid
2) oxidative decarboxylation: Cleaves off carboxyl and replaces with with CoA
- yield acetyl CoA, acetoacetate, or propionyl Coa |
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Term
| Aromatic Amino Acid entry into metabolic pathwas |
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Definition
- requies oxygenases (involve O2)
- reactions may invoolve tetrahydrobiopterin (reductant) and NADPH |
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Term
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Definition
- can't fully degrade Phe and Tyr
- lack of homogentisate oxidase: breaks aromatic ring
- excretion of homogentisate = dark urine |
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Term
| Maply syrup urine disease |
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Definition
- defective branched-chain dehydrogenase
- can't oxidatively decarboxylate
- high branched chain AA in blood and urine |
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Term
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Definition
- no Phenylalanine hydroxylase
- can't convert Phe to Tyr
- high blood Phe
- severe mental retardation
- need Tyr-supplemented/low Phe diet |
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