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Foundations 1 > 1-15 Nitrogen Metabolism > Flashcards

1-15 Nitrogen Metabolism Flashcards

1
Q

role of glutamate in urea production

A

glutamate collects nitrogen from other AAs AA + a-ketoglutarate via TRANSAMINATION -> a-ketoacids + glutamate glutamate via GLUTAMATE DEHYDROGENASE -> NH4+ OR glutamate + OAA via TRANSAMINATION -> a-ketoglutarate + Aspartate NH4+ and aspartate feed into urea cycle = UREA :)

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2
Q

Transamination reaction

A

AA1 + alpha-ketoacid2 via TRANSAMINASE -> alpha-ketoacid1 + AA2 Aspartate + aketoglutarte -> OAA + glutamate AA that cannot do this: lys, thr, pro, HO-pro Requries vitamin B6 coenzyme (pyridoxal phosphate) to transfer Nitrogen

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3
Q

alanine aminotransferase rxn

A

glutamate + pyruvate via ALANINE AMINOTRANSFERASE -> alanine + alpha-ketoglutarate

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4
Q

aspartate aminotransferase rxn

A

glutamate + OAA -> aspartate + alphaketoglutarate able to feed in to TCA (OAA, AKG)

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5
Q

glutamate dehydrogenase

A

oxidative deamination, only AA that undergos rxn like this H2O + glutamate + NAD(P)+ via GLUTAMATE DEHYDROGENASE -> NH4+ + a-ketoglutartate + H+ + NAD(P)H NAD: oxidative deamination NADP: reductive amination

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6
Q

glucose/alanine Nitrogen transfering cycle

A

Liver: glucose exported to peripheral tissues Muscle: glucose->pyruvate/lactate->alanine (via Alanine aminotransferase) alanine exported to blood to liver Liver: alanine + a-ketoglutarate via ALT -> pyruvate + glutamate; glutamate via GLUTAMATE DEHYDROGENASE -> NH3 + a-ketoglutarate; NH3 -> urea

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7
Q

Purine nucleotide cycle in skeletal muscle

A

prolonged exercise induces ATP->ADP->AMP via AMP deaminase -> NH3 (to glutamine) + IMP IMP + Aspartate -> adenylosuccinate -> fumarate + AMP, cycles

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8
Q

glutamine transfer cycle between liver/peripheral tissues

A

peripheral tissue: a-ketoglutarate + NH4+ via GLUTAMATE DEHYDROGENASE -> glutamate; + NH4+ +ATP via GLUTAMINE SYNTHASE -> ADP + glutamine Blood: glutamine Liver: glutamine via GLUTAMINASE -> NH4+ + glutamate; via GDH -> NH4+ + a-KG both of the NH4+ feed in to urea cycle

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9
Q

sources of nitrogen for urea cycle

A

muscle: aspartate / purine nucleotide cycle -> fumarate + NH4+ Gut: AAs via bacteria -> urea -> NH4+ Glutamate via Glutamate dehydrogenase -> a-KG + NH4+ Glutamine via Glutaminase ->Glutamate + NH4+ Asparagine via Asparaginase -> aspartate + NH4+ Serine via SERINE DEHYDRATASE (PLP pyridoxal phosphate) -> pyruvate + NH4+ Threonine via PLP -> a-ketobutyrate + NH4+ Histidine ->urocanate + NH4+

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10
Q

Urea cycle

A

mito: 1. CO2 + H2O -> HCO3- + NH4+; +2ATP via CARBAMOYL PHOSPHATE SYNTHETASE 1 (CPS1) -> 2ADP + 2 Pi + carbamoyl phosphate 2. carbamoyl phosphate + ornithine via ORNITHINE TRANSCARBAMOYLASE -> citrulline 3. citrulline exits mito via channel to cytosol) cytosol: 4. citrulline + aspartate +2ATP via ARGININOSUCCINATE SYNTHETASE -> 2AMP + PPi + Argininosuccinate 5. Argininosuccinate via ARGININOSUCCINATE LYASE -> Fumarate + Arginine 6. Arginine + H2O via ARGINASE -> Urea + ornithine 7. ornithine enters mito via channel to continue cycle; urea excreted in urine Summary: ammonia input from aspartate and mitochondria respiration

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11
Q

Regulation of CPS1

A

Glutamate + AcetylCoA *+regulated by Arginine) -> N-acetyl glutamate (+ allosteric regulator of CPS1) CO2 + NH4+ + 2ATP via CARBAMOYL PHOSPHATE SYNTHETASE -> 2 ADP + 2Pi + carbamoyl phosphate

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12
Q

Krebs bicycle

A
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13
Q

essential AAs

A

Lysine

Isoleucine

Leucine

Threonine

Valine

Phenylalanine

Methionine

Histidine

Need to get from diet

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14
Q

degredation of branched chain AAs

A

Valine -> propionyl Coa

Isoleucine -> Acetyl COa + Propionyl coA

Leucine -> Acetyl Coa + Acetoacetate

If can form: propinoyl = gluconeogenic

If can form acetyl coa or acetoacetate = ketogenic

common process in muscles

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15
Q

Serine synth/degrade

A

glucose—-> 3-phosphoglycerate—-> serine

serine—-> pep->pyruvate

*involves intermeditates of glycolysis and self regulates

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16
Q

metabolism of glycine

A

serine <-via SERINE HYDROXYMETHYL TRANSFERASE PLP> glycine

threonine -> glycine -> CO2 + NH4+

glycine->*oxalate (kidney stones) or a-KG–>H2O + CO2

*major way to degrade

17
Q

Cysteine synth/degrade

A

serine + methionine —> cysteine —>NH4 to urea, carbohydrates or GAGs, sulfate in urine

18
Q

degradation of phenylalanine and tyrosine

A

phenylalanine via PHENYLALANINE HYDROXYLASE (PKU deficient enzyme) -> tyrosine —–> Fumarate (TCA) + Acetoacetate

19
Q

Synth of non-essential AAs

20
Q

Non-essential AAs (formed from)

A

Asparagine (glutamine)

aspartate (OAA)

Glycine (Glucose/serine)

Serine (glucose)

Cysteine (Glucose/serine)

Alanine (Pyruvate)

Tyrosine (phenylalanine)

Glutamine (a-KG/glutamate)

Glutamate (a-KG)

Proline (glutamate semialdehyde)

Arginine (glutamate semialdehyde)

21
Q

Sources of carbones in purines:

Pyrimidines:

A

purines: aspartate, glycine, glutamine amide N

glutamine amide N, aspartate

22
Q

purine synthesis

A

PPP -> ribose 5-phosphate + ATP via PRPP SYNTHETASE -> AMP + PRPP

PRPP + glumaine ——> IMP

IMP + GTP + Asparatate -> AMP*

IMP + ATP + Glutamine -> GMP*

*reciprocally regulate each other to keep synth levels equal

AAs that make carbon skeleton: aspartate, glutamine, glycine

23
Q

Ribose to deoxyribose

A

must be done at Dinucleotide stage! (NDP->dNDP) via RIBONUCLEOTIDE REDUCTASE

24
Q

purine nucleotide cycle in muscle

A

important source of E during exercise

Aspartate (enters) + IMP + GTP (enters) -> GDP (exits) + P (exits) + Adenylosuccinate -> fumurate (exits to TCA) + AMP -> NH3 (exits) -> IMP

25
Q

salvage of purine bases

A

diet gives free bases

26
Q

synth of pyrimidine nucleotides

A

glutamine + CO2 + 2 ATP via CPS2 -> carbamoyl phosphate (CAP) ——-> UMP -> UDP -> UTP + glutamine -> CTP

purine nucleotides give negative feedback, PRPP give positive feedback on initial conversion to CAP

27
Q

Degredation of purines

A

GMP / AMP —-> Xanthine -> uric acid (crystalizes to cause Gout) degraded in intestinal epithelial to urine

excess purines in: meat, seafood, fructose, and alcohol

28
Q

degredation and salvage of pyrimidines

A

cytosine —-> alanine

thymine —–> aminoisobutyrate -> succinyl CoA

(free base) thymine -> thymidine (nucleoside)

(free base) uracil or cytosine -> uridine or cytidine (nucleoside)

29
Q

the one-carbon pool

A

sources: serine***, glycine, histidine, formaldehyde, formate ADD TO TETRAHYDROFOLATE TO FORM:
products: formyl, methylene, methyl ADD TO PRECURSORS TO FORM

recipients of carbons: dRMP, serine, purines, B12

***major donor

30
Q

reduction of folate

A

folate + NADPH via DIHYDROFOLATE REDUCTASE* -> NADP+ + dihydrofolate (rxn again) -> Tetrahydrofolate

*important enzyme

31
Q

Methyl trap hypothesis

A
  1. tetrahydrofolate-methyl + B12 -> FH4 + B12-methyl
  2. B12-methyl +homocysteine -> methionine
  3. methionine + ATP -> SAM (s-adenosylmethionine, activated methyl group)
  4. SAM + precursor -> precursor-methyl + SAH
  5. SAH -> Adenosine (exits) + homocysteine (cycles back for B12-methyl)

transfering methyl groups to oxygen or nitrogen on acceptor

32
Q

reactions of vitamin B12

A
  1. Homocysteine +B12-CH3 -> methionine + B12
  2. Methylmalonyl CoA + B12 -> Succinyl CoA
33
Q

formation of SAM

A

methionine + ATP+H2O via METHIONINE ADENOSYLTRANSFERASE -> PPi + Pi + S-adenosyl-methionine (“activated methionine)

34
Q

hyperhomocysteinemia

A

defects in cystathionine b synthase

Foundations 1 (41 decks)

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