Nitrogen metabolism

Question 1

Essential a.a.

Answer 1

• PVT TIM HALL
• Phenyalanine
• Valine
• Tryptophan
• Threonine
• Isoleucine
• Methionine
• Histidine
• Arginine
• Leucine
• Lysine
• Cys & Tyr become essential if Met & Phe become limiting in the diet, respectively
• Arg is conditionally essential: children require it in their diet

Question 2

2 major pathways for intracell protein degradation

Answer 2

• PEST sequences: Pro, Glu, Ser & Thr have short T1/2
  1. Lysosomal proteolysis:
• ATP-INDEPENDENT
• digestion of proteins brought into cell (extracell) via receptor-mediaetd endocytosis, eg. LDL & other plasma proteins
• Phagocytosis: cell defence from invading pathogenic organisms, dead cells & wound debris, eg., proteases digest ingested bacterial proteins or apoptotic cells
• Nucleases, phosphatases, glycosidases, esterases & proteases (cathepsins); only active at pH=5
• proteins NOT tagged

2. Ubiquitin-proteosome pathway

• REQUIRES ATP
• C-terminal Glycine residue of ubiquitin linked to an Epsilon-amino group of the target protein (intracell)
• Tagged by polyubiquitin

Question 3

Intestinal AA Absorption

Answer 3

• semi-specific AA transporters: Na+ -dependent secondary active transport mechanism

1. Neutral AA
2. Pro & HydroxyPro
3. Acidic AA
4. Basic AA

Question 4

Kidney’s Rebasorption of AA

Answer 4

• AA in circulation freely filtered into tubules
• Na+/K+ ATPase (3 Na+ out/2 K+ in) establishes an electrochemical gradient on the membrane
• Filtered aa reabsorbed into blood stream by specific AA transporters (Na+-amino acid co-transport)
• Initial state: pump open to inside

1. 3 Na+ are taken from inside ()
2. ATP phosphorylase alpha subunits
3. Conformational change following phosphorylation expels 3 Na+ to outside
4. Pump open to outside, read to start 2nd half of cycle
5. Dephosphorylation triggers conformational change
6. 2 K+ expelled to inside: pump returns to initial state

Question 5

Glucogenic AA

Answer 5

• Alanin
• Arginine
• Asparagine
• Aspartate
• Cysteine
• Glutamate
• Glutamine
• Glycine
• Histidine
• Proline
• Serine
• Methionine
• Threonine
• Valine

Question 6

Glucogenic & Ketogenic AA

Answer 6

• Tyrosine
• Isoleucine
• Phenyalanine
• Tryptophan

Question 7

Ketogenic

Answer 7

• Leucine
• Lysine

Question 8

Glutamate Metabolism

Answer 8

• Glutamate is the only AA that undergoes rapid deamination & essential to remove Nitrogen from body
• Some aminotransferases use alpha-ketoglutarate as the acceptor to form glutamate
• Sequential Action of Transamination (Aminotransferases) & Deamination (GDH)

Question 9

Cofactors for GDH

Answer 9

• NAD+ used in Oxidative Deamination
• NADPH used for Reductive Amination
• ADP activates GDH
• GTP inhibits

Question 10

Glutamate Metabolism: Transport of free ammonia to the Liver

Answer 10

• Urea cycle enzmes primarly found in liver
• All ammonia must be transported to liver
• Glutamine Synthase:
  
  • Found in most tissues especially the brain
  • Glu + NH3 + ATP -> Glutamine + ADP + Pi
• Glutaminase:
  
  • Liver, kidney
  • Glutamine + H2O -> Glu + NH3

Question 11

Kidney Glutamine roles

Answer 11

• Glutaminases increaes H+ excretion
• H+ + NH3 -> NH4+
• acts to buffer urine

Question 12

Alanine Metabolism

Answer 12

• Pyruvate readily available in muscle & transaminated to ALANINE

Question 13

Glucose-Alanine Cycle

Answer 13

• On arriving at Liver, alanine is transaminated back into pyruvate and Nitrogen will be used for urea synthesis
• Prevents toxic levels of ammonia in muscle
• Pyruvate formed used for GNG
• Cycle especially active during starvation