Chapter 11 Catabolism of Protein

protein putrefactionAAdeamination ammoniaurea-AA decarboxylationone carbon unit AA

Proteinp291 23

nitrogen balance 1 Total N Balance

2Positive N Balance

3Negative N Balance # concept of nitrogen balance:

Protein 3050g - Total N Balance 7080g 1.05g/Kg

300-500400--500100-200125-200(5050-10025-50),1005025

10030077(150:1)2.41

Definition: proteinEAA classcontentproportion EAAIleMetValLeuTrpPheThrLys NEAA semi-essential AA/conditionally essential AA ArgHis

15.6 16.6 36.3 28.2 () 16.7 19.1 21.3 50.5 15.5 26.4 26.2 18.9 15.4 () 20.3 () 17.3 17.0 2l 2 21.5 18.2 16.5 () 76.5 14.7 16.4 100

EAAmg/kg

(Physiological Value of Protein):

(Protein Complementarity):

pepsin trypsinchymotrypsin elastasecarboxypeptidase A/B enterokinaseaminopeptidase dipeptidase

PH 8.0~9.0 8.0~9.0 8.8 A 7.4 B 8.0

peptideAla5, Lys1, Phe124-DNFBpeptideproteinN-terminal AADNFB-AlatrypsintripeptideLys1 Ala2tetrapeptideAla3 Phe1peptidechymotrypsinhexapeptideAApeptideprimary structure

95%protein oligopeptide dipeptide AA

carrier proteinVarious AA carrier proteins nonpolar AA carriers basic AA carriers: acidic AA carriers sub-AA and Gly carriersProGly

Absorption of dipeptides and tripeptides

glutamyl cycle - GSH

- GSH

protein NH3R-CH2-COOHCO2R-CH2-NH2hydroxybenzenes, indoles, H2S, CH4

Dietary proteinTissue protein amination of -keto acidsdegradation Synthesis 85% NEAA Digest,absorptiondeaminationamines NH3 -keto acidsoxidation Glucose, fatsNEAAdecarboxylationAA metabolic poolurea other active substancesSummary of AA Catabolismspecifically

# leading pathway of AA degradation1. transaminaton

2. oxidative deamination

3. transdeamination

4. purine nucleotide cycle AAammonia-keto acid

1. Alanine Aminotransferase, ALT or Glutamate-pyruvate Transferase, GPT Aspartate Aminotransferase, AST or Glutamate-oxaloacetate Transferase, GOT

Clinical roles of detecting ALT and AST:

Enzymes: L-amino acid oxidase D-amino acid oxidase L-glutamate dehydrogenase(GDH)

GDH

Glu

Biological roles AA

NEAA

Purine Nucleotide Cycle

Gln (kidney)Blood Ammonia

Ammonia Absorption: NH3 NH4+H+OH- NH3NH4+NH3NH4+pHpH6NH3pH6 ammonia

Transportation of AmmoniaWhy

How to transport

GlutaminaseH2O+NH3Gln synthetaseATPADP+Pi1Ammonia Carrying by Gln:

ammoniaGlnammoniaureaammoniaH+NH4+Glnammonia ammonia

2Alanine-glucose Cycle

Roles eliminating toxicity of ammonia

supplying energy for muscle

Synthesis of Urea /Ornithine Cycle /Urea Cycle /Krebs-Henseleit Cycle1932, , Krebsammonia(>80%

1.Process of Urea Synthesis

Total Reaction Formula:

2. Biological functions of Urea Cycle:Thorough removal of ammonia

3. Summary of Urea Cycle:1 urea:2NH3,1CO2,3ATP1NH3AANH3,NH3AspUreaammoniaNPNureaammoniaAAureaNPNCPS-CPS-

CPS CPS

Site mitochondria cytosol N source NH3 Gln Products urea pyrimidine CPS : carbomoyl phosphate synthetase

3. High blood ammonia & Ammonia poisoning

Metabolism of -keto acidsaminationtransamination conversionoxidation

Glucogenic AA and Ketogenic AA

CoA -CoAPEP-CoACO2CO2T A C

Leu

Lys

DecarboxylationAAdecarboxylaseamine+CO2()

Common important amines:Glu-amino butyric acidGABATry5-hydroxy tryptamine5-HTHishistamineCystaurineOrn and Metpolyamines

1GABA

25-HT5-5-HT

3 Histamine

4catecholamines CH2CHNH2COOHCH2CHNH2COOHOHCH2CHNH2

CH2NH2 HCOH CH2NH-CH3 HCOH

OHOH

OH OH

OH OH OHOH

DOPADOPA CO2---N--CH3

5Taurine

6Polyamines

Metabolism of individual AA

one carbon unit sulfur-containing AA aromatic AA branched chain AA

Conceptsome AA one carbon groupsClasses -CH3 -CH2- -CH= -HC=O -CH=NH Carrier tetrahydrofolate (FH4) FH4N5N10One Carbon Unit(OCU)

Formation and structure of FH4Sites binding OCU

OCUFH4

OCU generation & conversion

Biological functions of OCU metabolism: OCU OCU OCUAA

Sulfur-containing AAClassesMet/Cyscysteine Cystine

Metabolism of Met+

1Met cycleRHR-CH3VitB12CH3-:

OCU generation & conversion

2Biological roles: CH3 FH4

B12folate

Metabolism of Cys and CystineCystineCysTaurine + NH3 + H2SH2SO43--5-PAPSGSHconversion

1Conversion of Cys and Cystine Cys Cystine

2Cysactive H2SO4

3CysGSHenzymesproteins

Aromatic AA (AAA)Classes of AAAPheTyr Trp

Phe & Tyr:Phe Tyr

Phe transforming into Tyr

(phenyl ketonuria, PKU)Phe Tyr transaminationPKU,

PKU60%

Tyr Tyr

Tyrmelanin

TyrDOPADANEE

Parkinsons disease DA60 601.71.6400170 1997411

Tyr

Summary of Phe & Tyr metabolism

Trp: 5-HTCOUA

Branched chain AA

PKU

CoA -CoAPEP-CoACO2CO2T A C

AA metabolic poolDietary proteinTissue proteinNEAATissue protein-AmineN

2Alanine-glucose Cycle