Catabolism of tissue protein,Protein degradation ط Essential and nonessential amino acids ط Protein turnover in a regular manner, Apoptosis ط Nitrogen balance, positive and negative nitrogen balance, causes D

Introduction · Nitrogen (N2) exists in the atmosphere: 1. fig11.1, nitrogen in air (NO2–) == reduced by microorganisms ==> air (NO3–) 2. air (NO3–) == incorporated into AAs/prt ==> plant/animal (NH3) · Table 11.1, Most AAs obtained from diet (essential) and the body can synth others (non-essential)

Nitrogen (N2) Balance Incorporation of nitrogen (N2) into AAs gives a dietary balance if enters the human body: 1. Balanced N2 (body): excretion of excess N2 & N2 of prt turnover (synth:deg) 2. Negative N2 balance: increase excretion of N2 as urea when C is needed for gluconeogenesis during: Starvation Poor essential AA (EAA) diet intake Certain diseases 3. Positive N2 balance: decrease excretion of N2 and incorporation into prt during: Growing children (cys & arg are NEAA in childhood) Pregnancy Re-feeding after starvation

1. In a regular basis (apoptosis): protein is degraded continuously (NEAA biosynth) Apoptosis (planned cell death) during regular turnover of prt (synth:deg) a) INS ½-life – 1 hr b) Hb ½-life – months c) Majority of prts have ½-life of days Selection occur by marking with Ubiquitin (oligopeptide, 76 A groups) a) Lysosomal, Ca++-dependant Enz process b) Non-lysosomal, ATP-dependant 3 Enz-complex process Protein Degradation

2. fig11.20, When energy is needed (proteolysis): Proteolysis (prt deg) is a respond to starvation, trauma, burns, septicaemia cachexia (tumor) & acidosis Majority of prts in muscle, and most AAs in muscle are BC-AA (val, leu, ile) First step is transamination (aminotrasnferase, A T-ase) a) Amino Acid  GltDH (α-KG => Glt)  Keto Acid (C is needed for energy) b) Glt  Glt-ase (+NH4+)  Gln (transport N2 to liver for urea synth) c) pyr  Ala T-ase (Glt => α-KG)  ala (to liver for urea synth / gluconeogenesis) Amino group “NH3“ (Gln, urea) to kidney (urea / ammonia excretion) * in cachexia, there is high glucagon secretion causing wasting of plasma AA (low) due to increase uptake by liver and secretion by kidney. This leads to further protein breakdown from muscle (protolysis) to compensate plasma AA * in acidosis, high pH shunts Gln from liver to kidney to conserve bicarbonate (HCO3– ) for formation of urea

Some important protein reactions ط Transamination reactions, mechanism of actin of transaminases, Pyridoxal phosphate as cofactor ط Degradation and transport of tissue protein D

a) Transamination: transfer 1 amino group from an AA to another AA fig11.4, NEAA: Ala (NH3) + α-KG  Amino transferase  Pyr + Glt (NH3) Pyr to TCA cycle, Glt to urea cycle – reversal: Ala to prt synth (if not met by diet) fig11.5, EAA: Val (NH3) + α-KG  Amino transferase  α-KIV+ Glt (NH3) α-KIV to SCoA – reversal only during α-KIV drug therapy b) Coupled Transamination fig11.6, Ala (NH3) + α-KG  Amino transferase  Pyr + Glt (NH3) Glt (NH3) + OA  Amino transferase  α-KG + Asp (NH3) Amino Reactions

* fig11.7, PyPh (Vit B6) is a cofactor for amino transferases fig11.8, example: PyPh attach to Lys active site by Schiff base (ionic/hydrophobic bond) fig11.9, different forms of PyPh (Asp & Glt transamination) fig11.10, carboxyl & hydroxyl groups (PyPh-dependent) can be eliminated, other than amino group * Thr & Lys do not use transamination Pyridoxal Phosphate

a) fig11.11, α-Keto/Amino Acid Cycle α-KG  GltDH (–NH4+/NADPH)  Glt fig11.13, ammonia incorporation is stimulated by ATP/GTP Glt  GltDH (+NH4+/NADH)  α-KG fig11.13, ammonia release is stimulated by ADP/GDP b) fig11.14 – 11.15, Glutamine Cycle Glt  Glt Synthetase (–NH4+/ATP)  Gln (carrier of ammonia) Gln  Glt-ase (+NH4+)  Glt (ammonia released) Ammonia Production

Release of Amonia by Other Reactions c) fig11.19, Oxidative Deamination (L-AA) α-Amino Acid  AA Oxidase (–FMN/ +H2O2)  α-Imino Acid  Deamination (+NH3)  α-Keto Acid D-AA oxidase by intestinal bacteria d) fig, Non Oxidative Deamination Serine  Ser DH è a-Imino Acid  Deamination (+NH3)  Pyruvic Acid e) fig, Amino Desulfhydration Cystein è Cys DS  a-Imino Acid  Deamination (+NH3)  Pyruvic Acid f) fig, Amino Decarboxylation · Histidine  His Decarboxylase (–CO2)  Histamine · Serine  Ser Decarboxylase (–CO2)  Ethanolamine * Ammonia released in kidney  excreted * Ammonia released in liver  used to produce urea