The proteins metabolism

Biochemistry for nurses

1. Biochemistry for nurses: Unit 3 THE PROTEIN METABOLISM

2. Biochemistry for nurses: Unit 3 Protein Turnover = Continuous degradation and synthesis of proteins . Replacement of 1-2% of the total body protein each day Amino acid pool = Accumulation of free AA in the liver and the blood : 75 % of liberated AA from tissue proteins are reutilized Degradation ( catabolism of AA) = Excess of AA are not stored ! but rapidly degraded for the synthesis of glucose ( glycolosis ) and lipids . Degradation of excess AA causes an excess of nitrogen . Waste = Nitrogen excess is transformed into urea (80%) and ammonium (NH 4 + ) in order to be thrown away in the urine. ( Liver and Blood)

3. Biochemistry for nurses: Unit 3 NITROGEN BALANCE The amino acids are the main source of Nitrogen . Nitrogen balance (NB) is a comparaison between nitrogen intake (Dietary proteins) and nitrogen loss (indigested proteins in feces, waste excretion as urea (80%) and ammonia (NH 4 + ) in the urine). - For normal adult: Ingested nitrogen = excreted nitrogen Positive NB = Ingested nitrogen > excreted nitrogen (children growth, pregnancy) Negative NB = Ingested nitrogen < excreted nitrogen (may follow surgery, advanced cancer, marasmus)

4. Biochemistry for nurses: Unit 3 Protein Turnover = Continuous degradation and synthesis of proteins . Replacement of 1-2% of the total body protein each day Amino acid pool = Accumulation of free AA in the liver and the blood : 75 % of liberated AA from tissue proteins are reutilized Degradation ( catabolism of AA) = Excess of AA are not stored ! but rapidly degraded for the synthesis of glucose ( glycolosis ) and lipids . Degradation of excess AA causes an excess of nitrogen . Waste = Nitrogen excess is transformed into urea (80%) and ammonium (NH 4 + ) in order to be thrown away in the urine. ( Liver and Blood)

5. Biochemistry for nurses: Unit 3 Digestion and absorption of proteins Digestion = degradation of the protein into AA by the digestive system to make it absorbable by intestine. Absorption = Transfert of the AA from the intestine to the blood

6. Biochemistry for nurses: Unit 3 Proteins are digested by proteases and peptidases . Protein digestion starts in the stomach. PEPSIN is an endoprotease which degrades food proteins in the stomach.

7. Biochemistry for nurses: Unit 3

8. Biochemistry for nurses: Unit 3 TRYPSIN = Endopeptidase cleaves the peptide bond at the carboxyl side of the Lysine and Arginine . CHYMOTRYPSIN = Endopeptidase cleaves the peptide bond at the carboxyl side of the Tryptophan , Tyrosine and Phenylalanine .

9. Biochemistry for nurses: Unit 3 Protein digestion is completed in the small intestine by brush border enzymes carboxypeptidase , aminopeptidase , and dipeptidase .

10. Biochemistry for nurses: Unit 3

11. Biochemistry for nurses: Unit 3 Practise ENDOPEPTIDASE: Trypsin = cleaves at the COOH side of Lysine and Arginine. Chymotrypsin = cleaves at the COOH side of Tryptophan, Tyrosine and Phenylalanine. Tri or Dipeptidase = cleaves between AA of tri or dipeptides EXOPEPTIDASE: Carboxypeptidase = removes AA from the COOH end Aminopeptidase = removes AA from the NH 2 end H 2 N -Val-Cys-Ala-Leu-Lys-Val-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala- COOH Trypsin + Chymotrypsin ? Tripeptidase + Aminopeptidase + Carboxypeptidase Final products ?

12. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys-Val-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala- COOH Trypsin

13. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys-Val-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala- COOH Chymotrypsin Trypsin

14. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys-Val-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala- COOH Chymotrypsin Trypsin H 2 N -Val-Cys-Ala-Leu-Lys- COOH H 2 N -Val-Glu-Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr-Pro-Lys- COOH H 2 N -Ala- COOH

15. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys- COOH H 2 N -Val-Glu-Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr-Pro-Lys- COOH H 2 N -Ala- COOH Tripeptidase

16. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys- COOH H 2 N -Val-Glu-Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr-Pro-Lys- COOH H 2 N -Ala- COOH Tripeptidase + Aminopeptidase

17. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys- COOH H 2 N -Val-Glu-Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr-Pro-Lys- COOH H 2 N -Ala- COOH Tripeptidase + Aminopeptidase + Carboxypeptidase

18. Biochemistry for nurses: Unit 3 H 2 N -Val-Cys-Ala-Leu-Lys- COOH H 2 N -Val-Glu-Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr-Pro-Lys- COOH H 2 N -Ala- COOH Tripeptidase + Aminopeptidase + Carboxypeptidase H 2 N -Val- COOH H 2 N -Cys-Ala-Leu- COOH H 2 N -Lys- COOH H 2 N -Val- COOH H 2 N -Glu- COOH H 2 N -Arg- COOH H 2 N -Gly-Phe- COOH H 2 N -Phe- COOH H 2 N -Tyr- COOH H 2 N -Thr- COOH H 2 N -Pro- COOH H 2 N -Lys- COOH H 2 N -Ala- COOH

19. Biochemistry for nurses: Unit 3 Summary:

20. Biochemistry for nurses: Unit 3 Protein Turnover = Continuous degradation and synthesis of proteins. Replacement of 1-2% of the total body protein each day Amino acid pool = Dietary proteins and the catabolism of tissue proteins provide free AA. 75 % of liberated AA from tissue proteins are reutilized. Degradation (catabolism of AA) = Excess of AA are not stored! but rapidly degraded for the synthesis of glucose (glycolosis) and lipids. Degradation of excess AA causes an excess of nitrogen . Waste = Nitrogen excess is transformed into urea (80%) and ammonium (NH 4 + ) in order to be thrown away in the urine. ( Liver and Blood)

21. Biochemistry for nurses: Unit 3 Definition of the Keto Acid The deamination of an Amino Acid (= removing of the amino group) forms the corresponding Keto Acid . The Keto acid is also called «  the carbon skeleton  »

22. Biochemistry for nurses: Unit 3 Definition of the Keto Acid The deamination of an Amino Acid (= removing of the amino group) forms the corresponding Keto Acid . The Keto acid is also called «  the carbon skeleton  » WASTE REUSED!

23. Biochemistry for nurses: Unit 3 BIOSYNTHESIS of UREA Biosynthesis of urea is composed by 4 stages: Transamination Oxidative deamination of Glutamate Ammonia transport Reactions of the urea cycle. 80% of the excess amino acid nitrogen forms Urea in order to be thrown away in the urine. Tissues Liver

24. Biochemistry for nurses: Unit 3 Transamination Transfert of the α-amino group (NH 2 ) to the ketoglutarate to give GLUTAMATE The reaction is reversible. The reaction is catalysed by an enzyme ( Aminotransferase ) in presence of a co-enzyme (PLP = Vit B 6 ) (TISSUES)

25. Biochemistry for nurses: Unit 3 Oxidative deamination of Glutamate Formation of ammonia (NH 3 ) from the amino group (NH 2 ) of the Glutamate by oxidative deamination. Glutamate is the only Amino Acid that undergoes oxidative deamination. Enzyme = Glutamate Dehydrogenase (GDH); Coenzyme = NAD + (LIVER)

26. Biochemistry for nurses: Unit 3 Amino acid oxidase reaction The amino acid oxidase (AAO) of liver and kidney removes the nitrogen as ammonium ion (NH 4 + ). Conversion of Amino Acids to an Imino acids which are decomposed to a Keto acid with release of NH 4 + . Enzyme = AAO ; Coenzyme = Flavin The reduced Flavin is reoxidized by O 2 , forming hydrogen peroxide (H 2 O 2 ) which then is split to O 2 and H 2 O by CATALASE . (LIVER and KIDNEY)

27. Biochemistry for nurses: Unit 3 Ammonia (NH 3 ) Transport NH 3 is very toxic to the nervous system! The NH 3 produced by tissue are rapidly removed from circulation by the Liver and converted to UREA Only traces (10-20 uG / dL ) of NH 3 are present in blood in normal conditions Liver damage and metabolic disorders are associated with elevated concentration of NH 3 in the blood . In case of CIRRHOSIS ( hepatic disease ), NH 3 rises to toxic levels , consequently : Tremor , blurred , coma and ultimately death . The transport of NH 3 from the tissue to the liver is done by GLUTAMATE or GLUTAMINE as nontoxic forms .

28. Biochemistry for nurses: Unit 3 Glutamine Synthase fixes NH 3 as Glutamine . NH 3 is fixed by GLUTAMATE to give GLUTAMINE Enzyme = Glutamine Synthase ( inside tissue mitochondria ) That reaction needs ENERGY to work ! ( hydrolysis of ATP ) Tissues

29. Biochemistry for nurses: Unit 3 UREA CYCLE UREA is the major end product of Nitrogen catabolism in human body. Synthesis of 1 molecule of UREA requires : 3 molecules of ATP ( Energy !) 1 molecule of NH4+ 1 molecule of α - amino group (NH2) of Aspartate 5 enzymes catalyse the Urea Cycle in the liver cells : Carbamoyl Phosphate Synthase I Ornithine Transcarbamoylase Argininosuccinic Acid Synthase Argininosuccinase Arginase

30. Biochemistry for nurses: Unit 3

31. Biochemistry for nurses: Unit 3 Summary of the Urea Cycle 2 NH 3 + CO 2 + 3 ATP UREA + 2 ADP + P i + AMP + P i Liver

32. Biochemistry for nurses: Unit 3 Summary of the ammonia elimination Amino acids degradation Amino group Keto acids «  carbon skeletton  » Synthesis of glucoses and lipids

33. Biochemistry for nurses: Unit 3 Summary of the ammonia elimination 1 – 2 % of the body proteins are degraded and renewed daily Ammonia (NH 3 ) is highly toxic . Ammonia (NH 3 ) is converted to Urea Glutamine synthase converts NH 3 to nontoxic glutamine Glutaminase releases NH 3 for use in urea synthesis NH 3 , CO 2 and the amide nitrogen of aspartate provide the atoms of urea Hepatic urea synthesis takes place in part in the mitochondrial matrix and in part in the cytosol.

34. Biochemistry for nurses: Unit 3 Clinical correlation

35. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis

36. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis [NH 3 ] in blood increases

37. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis [NH 3 ] in blood increases NH 3 intoxication Intoxication is more severe when the urea synthesis is blocked at reactions 1 or 2

38. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis [NH 3 ] in blood increases NH 3 intoxication Intoxication is more severe when the urea synthesis is blocked at reactions 1 or 2 Clinical symptoms: Vomiting Avoidance of high protein foods Irritability Lethargy Mental Retardation (Brain damage)

39. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis [NH 3 ] in blood increases NH 3 intoxication Intoxication is more severe when the urea synthesis is blocked at reactions 1 or 2 Clinical Treatments: Low protein diet ingested Frequent small meals to avoid sudden increase in blood of the NH 3 levels. Clinical symptoms: Vomiting Avoidance of high protein foods Irritability Lethargy Mental Retardation (Brain damage)

40. Biochemistry for nurses: Unit 3 Metabolic disorders of urea synthesis Extremely rare: Dysfunction of enzymes Disorders in urea synthesis [NH 3 ] in blood increases NH 3 intoxication Intoxication is more severe when the urea synthesis is blocked at reactions 1 or 2 Clinical Treatments: Low protein diet ingested Frequent small meals to avoid sudden increase in blood of the NH 3 levels. Clinical improvement and minimization of Brain damage. Clinical symptoms: Vomiting Avoidance of high protein foods Irritability Lethargy Mental Retardation (Brain damage)