html5-img
1 / 19

Amino acid metabolism ·        Nitrogen balance protein catabolism,

Amino acid metabolism ·        Nitrogen balance protein catabolism, synthesis biosynthesis normal N balance: N ingested = N excreted negative N balance: N ingested < N excreted positive N balance: N ingested > N excreted. (NH 4 + . urea).

chidi
Download Presentation

Amino acid metabolism ·        Nitrogen balance protein catabolism,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Amino acid metabolism ·        Nitrogen balance protein catabolism, synthesis biosynthesis normal N balance: N ingested = N excreted negative N balance: N ingested < N excreted positive N balance: N ingested > N excreted (NH4+. urea) Dietary protein amino acid pool N excretion

  2. Amino acid catabolism ·        accounts for ~ 10% of energy requirement of adults ·       When: ·       excess protein in diet ·        protein degradation exceeds demand for new protein ·        starvation when carbohydrates are not available ·        protein storing seeds such as beans, peas, etc. ·        Glucogenic vs ketogenic amino acids ·        ketogenic: yield AcCoA or AcAc as end products of catabolism - leu, lys ·        glucogenic: are degraded to pyruvate or a member of the TCA cycle (succinylCoA, OAA, a-ketoglutarate, fumarate). In absence of sugars, glucogenic amino acids permit continued oxidation of fatty acids by maintaining TCA cycle intermediates. - ile, phe, tyr, trp ·        glucogenic and ketogenic: yield both ketogenic and glucogenic products. - all others

  3. 2. 4. • N catabolism • General strategy: • ·     removal of N from amino acid by transamination (generally • first or second step of amino acid catabolic pathways) and • ·        collection of N in glutamic acid • ·        deamination of glutamic acid with release of NH4+ • -glutamate dehydrogenase 3. Collection of N in glutamine or alanine for delivery to liver ·removal of NH4+ by : i. secretion; or ii. conversion to urea or other less toxic form.

  4. to e-amino of lysine Vitamine B6 family Pyridoxine Pyridoxal Pyridoxamine Pyridoxal phosphate See Horton: page 212 section 7.7 pyridoxal phosphate

  5. Transamination reaction R1 H- C-NH3+ COO- see text p 537 and fig 17.7. Lys-protein NH + a-aminoacid-1 Schiff base with enzyme R1 H-C-COO- Lys-protein NH Schiff base with substrate

  6. R1 H- C- COO- O R1 H-C-COO- Lys-protein NH Schiff base with substrate Lys-protein NH2 + a-ketoacid-1

  7. R2 H- C- COO- O R2 H-C-COO- Lys-protein NH Schiff base with substrate Lys-protein NH2 + a-keto acid a-ketoacid-2

  8. R2 H- C-NH3+ COO- Lys-protein NH + a-amino acid-2 Schiff base with enzyme R2 H-C-COO- Lys-protein NH Schiff base with substrate

  9. Net reaction: e.g. alanine + a-ketoglutarate pyruvate + glutamate a-amino acid-1 + a-ketoacid-2 PLP a-amino acid-2 + a-ketoacid-1

  10. Alanine-glucose cycle Muscle glucose 2 pyruvate 2 a-aa 2 a-ka 2 alanine 2 alanine glucose Liver glucose 2 pyruvate 2 Glu 2 a-kG 2 NH4+ 2 alanine

  11. glutamate dehydrogenase (see p 533 for reaction) • - release or capture of NH4+ • ·        - located in mitochondria • ·        - operates near equilibrium amino acid + a-ketoglutar a-keto acid + glutamate glutamate + NAD + H2O a-ketoglutar +NADH + H+ + NH4+ amino acid + NAD + H2O a-keto acid +NADH + H+ + NH4+ NAD NADH glutamate + H2O a-ketoglutarate + NH4+ NADP NADPH

  12. 3. transport of N to the liver - glutamine synthetase - glutaminase - alanine/glucose cycle glutamate + NH4+ glutamine ATP ADP + Pi glutamine glutamate + NH4+ 1. Glutamine synthetase 2. Glutaminase Note: glutamate can be used for glucose synthesis. How?

  13. Pyr Glucose Ala 2NH4+ 2NH4+ 2Glu 2Glu’NH2 2a-KG Glu’NH2 Glu a-KG 4CO2 Glucose NH4+ KIDNEY HCO3 + H+ H2CO3 CO2 H2O MUSCLE NH4+ Glu’NH2 Pyr Glu a-ka Glucose a-aa Ala a-KG Urea LIVER

  14. Urea cycle Where: Liver: mito/cyto Why: disposal of N Immediate source of N: glutamate dehydrogenase glutaminase Fate of urea: liver kidney urine How much: ~ 30g urea / day

  15. NH4+ + HCO3- + 2 ATP H2N-C-OPO3-2 + Pi + 2 ADP O Reactions of urea cycle 1. Carbamyl phosphate synthetase I (mito) carbamyl phosphate • committed step • by N’Ac glutamate 2. Ornithine transcarbamylase (mito) Pi carbamyl phosphate ornithine citrulline

  16. 3. Arginosuccinate synthetase (cyto) + AMP + PPi ATP arginosuccinate 4. Arginosuccinate lyase (cyto) + fumarate arginine

  17. 5. Arginase (cyto) urea ornithine

  18. NH3+ aKG 2ATP HCO3 2ADP +Pi NADH + H+ NAD ornithine asparate glutamate MITO CYTO ornithine citrulline asparate glutamate ATP AMP + PPi fumarate See fig 17.26

  19. Interorgan relationships in N metabolism Epithelial cells of intestine Several steps Glu’NH2 cittruline Glu’NH2 Glu’NH2 Liver Kidney cittruline Arg Arginine Arginine Urea cycle Several steps Urea Ornithine 2 steps creatine glutamate To urine Muscle creatine P-creatine Several steps creatinine Adapted from Devlin, Biochemistry with Clinical Corrleation 4th ed.

More Related