• purine
• AA
• gut

aspartate

ammonia

Mechanism of synthesis of carbamoyl phosphate

• starts with carbon dioxide, ammonia, ATP
• via carbamoyl phosphatate synthetase, hydrolyze 2 ATP's
• produces carbamoyl phosphate and 2 ADP's

Methods of detoxification of ammonia in the peripheral tissues

• via ATP dependent interaction with Gln synthetase, converts Glu to Gln
• via

liver

GI

kidney

Fate of Gln in liver, GI, kidney

• converts Gln back to Glu and ammonia via glutaminase (involves water)
• kidney will excrete the ammonia
• liver deficates it out

glutaminase will increase its activity to buffer

Only place in body the complete urea cycle found

• ornithine combines with carbamoyl phosphate to form citrulline via ornithine transcarbamylase
• occurs in mitochondria

• citrulline combine with Asp to form arginosuccinate via arginosuccinate synthetase in a ATP hydrolysis dependent interaction
• forms AMP and PP
• occurs in cytosol

• arginosuccinate hydrolyzed to form fumaric acid and arginine via arginosuccinate lyase
• occurs in cytosol

• arginine hydrolyzed to from urea and ornithine (are starting product) via argininase
• occur in cytosol

• outer membrane- normal membrane
• inner membrane- impermeable to almost everything
  • ammonia and carbon dioxide are two of the few compounds that can cross this matrix

• allosteric activator of carbamoyl phosphate synthetase I (without it, enzyme has little activity) (really high after high protein meal)

GDH

CPS I

urea cycle

What is the carrier molecule for ammonia in the urea cycle

1. Phe taken in via the diet
2. two options
   1. break down into keto acid
   2. break down into Tyr
      1. produce T3/T4
      2. dopa/dopamine and norepi./epi.
      3. melanin
      4. fumarate/acetoacetate

1. via Phe monooxygenase, add oxygen using molecular oxygen as the source
   1. one oxygen in H2O
   2. one oxygen to Phe
2. Phe MO is fueled via conversion of tetrahydrobiopterin to dihydrobiopterin
3. produce tetrahydrobiopterin via dihydrobiopterin reductase
   1. involve oxidation of NADPH to NADP

Mechanism of catboloism of Tyr (emphasize what the end products are)

1. via Tyr aminotransferase dependent on alpha keto glutaric acid to produce p-hydroxyphenyl pyruvic acid
2. via hydroxyphenyl pyruvic acid dioxygeanse, leads to production of carbon dioxide from oxygen and homogentistic acid
3. via homogentistic acid dioxygenase, uses oxygen to produce fumarylacetoacetic acid
4. via hydrolase, produce acetoacetic acid and fumaric acid

Disease of defect in Phe monooxidase

• kills the uptake of and metabolism of Tyr and Trp (both are responsible for making very important neurotransmitters in the brain)

Cause of alcaptoneuria and clinical signs. Prognosis

• enzyme that breaks down homogentistic acid (HA dioxygenase) will be defective, leading to increase in homogentistic acid that is
• clinical sign- HA excreted in the urine (urine is black)
  • when homogenistic acid hits the air, turns into a black polymer
• prognosis- pretty benign

• cause- build up of branched chain alpha keto acid due to defect in branched chain alpha keto acid dehydrogenase

1. via branched chain amino transferase, converted AA to alpha keto acid
2. via branched chain alpha keto acid dehydrogenase, alpha keto acid produces carbon dioxide and CoA derivative

All three branched chain AA use the SAME ENZYMES!!!!!!

• supplied via diet
• produces:
  • serotonin
  • nicotinamide (precursor for NAD, NADH)
  • alanine/acetoacetate

1. via Trp MO, use oxygen
   1. one oxygen to water
   2. one to Trp
2. via dihyrdoxybiopterion reductase, oxidize NADPH to NADP and produce tetrahydroxybiopterion (give Trp MO its activity)
3. produces 5-hydroxyTrp
4. via PLP dependent decarboxylase, produce serotonin and carbon dioxide