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BIOC/DENT/PHCY 230 LECTURE 4

BIOC/DENT/PHCY 230 LECTURE 4. Nitrogen Metabolism. Many nitrogen containing compounds eg. Amino acids, nucleotides, porphyrins, neurotransmitters . There is no dedicated store for nitrogen or nitrogen compounds in humans. Nitrogen Balance.

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BIOC/DENT/PHCY 230 LECTURE 4

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  1. BIOC/DENT/PHCY 230 LECTURE 4

  2. Nitrogen Metabolism Many nitrogen containing compounds eg. Amino acids, nucleotides, porphyrins, neurotransmitters There is no dedicated store for nitrogen or nitrogen compounds in humans

  3. Nitrogen Balance An individual’s nitrogen balance is dependent on a combination of: 1) Dietary nitrogen intake 2) Physiological state Nitrogen balance status can be: 1) In balance 2) Positive 3) Negative

  4. Nitrogen intake = nitrogen excretion Dietary amino acids, nucleotides etc. Urine, faeces, hair and skin loss, perspiration 1) In balance

  5. 2) Positive Nitrogen intake > nitrogen excretion Possible causes: Childhood and adolescent growth Pregnancy Body building

  6. 3) Negative Nitrogen intake < nitrogen excretion Possible causes: Illness Starvation Post-surgery

  7. Amino acids are the major source of dietary N

  8. Excess or insufficient dietary amino acid intake leads to the catabolism of amino acids • Excess amino acids can be used for energy • Insufficient dietary amino acids lead to the catabolism of proteins • Insufficient dietary energy leads to the catabolism of proteins • For amino acids to be utilised for energy, they must have their a-amino groups removed

  9. Deamination of amino acids Deamination generates: a carbon skeleton a free amino group can be used for anabolic or catabolic reactions generally excreted

  10. GDH glutamate + NAD(P)+ + H2O a-ketoglutarate + NH4+ + NAD(P)H Some amino acids can be directly deaminated Serine, threonine and glutamate can be directly deaminated Glutamate deamination is catalysed by glutamate dehydrogenase (GDH)

  11. Glutamine can be deaminated in a two step process glutaminase glutamine + H2O glutamate + NH3 Glutamate is then deaminated by GDH

  12. GS glutamate + NH4+ + ATP glutamine + ADP + Pi Glutamine can also be synthesised from glutamate Glutamine synthesis is an energy requiring reaction The reaction is catalysed by glutamine synthetase (GS)

  13. Transamination Those amino acids that can not be directly deaminated have their amino groups transferred to specific substrates These substrates are keto acids found in intermediary metabolism a - ketoglutarate oxaloaceatate pyruvate CAC

  14. Addition of amino groups to these keto acids generates amino acids glutamate aspartate alanine a - ketoglutarate oxaloacetate pyruvate Most amino acids are deaminated by donating their a-amino acids to one of these keto acids Thus the deamination of most amino acids leads to the production of either glu, asp, ala or gln.

  15. glutamate a-keto acid a-KG a-amino acid glutamate aminotransferase An example transamination

  16. Pyridoxal phosphate Derived from vitamin B6 Takes part in all amino transferase reactions Forms a Schiff base intermediate with substrates

  17. Role of transamination in metabolism Transamination allows for: 1) the generation of amino acids in short supply 2) the provision of carbon skeletons for energy generation 3) the safe removal of excess amino groups

  18. Free ammonia is a by-product of brain metabolism The neurotransmitter GABA is inactivated by deamination GS glutamate + NH4+ + ATP glutamine + ADP + Pi However when ammonia concentrations are high: GDH a-ketoglutarate + NH4+ + NADPH glutamate + NADP+ + H2O • Brain requires large amounts of ATP • This must be generated via oxidative phosphorylation • Therefore the CAC must function efficiently

  19. ATP ADP + Pi 2ADP ATP + AMP AMP IMP + NH4+ AMP deaminase Free ammonia is also produced in muscle • Amino groups can be liberated: • during normal muscle turnover • during starvation • during severe muscle activity

  20. alanine aminotransferase glutamate + pyruvate a-ketoglutarate + alanine • Pyruvate is usually abundant in active muscle • Muscle uses pyruvate as an acceptor keto acid • Thus in muscle most amino groups are shuttled to alanine (via glutamate) • Alanine is then exported to the liver where the amino groups can be liberated

  21. AMP

  22. The take home message • Nitrogen balance status depends on the intake and use of N containing compounds • Excess N from amino acids must be excreted • A series of aminotransferase and deamination reactions shuttle nitrogen to appropriate molecules and tissues • Brain and muscle can generate large amounts of excess nitrogen as part of their metabolism • The liver is an important tissue for processing excess nitrogen

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