To easy to study

1. Urea Cycle
Dr. Deena Mendez
Associate Professor
Biochemistry

3. • Urea is the end product of protein (amino acid) metabolism.
• Ammonia (NH3) is the immediate end product of amino acid
metabolism
• However, NH3 is toxic to body.
• So, it enters liver where it is detoxified to urea in urea cycle.

4. Urea cycle
Tissue/organ: liver
Site: both in mitochondria & cytosol.
• First 2 reactions take place in mitochondria & remaining steps takes
place in cytosol.

6. Enzymes of urea cycle:
1) Carbamoyl Phosphate synthase I
2) Ornithine Transcarbamoylase
3) Argininosuccinate Synthetase
4) Argininosuccinase
5) Arginase

12. Clinical Significance of blood urea level
Normal blood urea level ranges 15-45 mg/ dL
I. Causes of increased blood urea level:
a. Pre-renal causes:
 High protein diet.
 Increases with age
 Dehydration as in diarrhea, vomiting.
 Increased cardiac output/ failure
 Increased catabolism of proteins as in fever and wasting diseases.

13. b. Renal causes:
 Nephritis
 Nephrotic syndrome
 Acute renal failure
 Chronic renal failure
 Polycystic kidney
 Hydronephrosis
c. Post-renal causes:
• Obstruction in the renal tract
• Enlargement of prostate
• Stones in bladder.

14. II. Causes of decreased blood urea level:
• Liver diseases due to decreased synthesis.

15. Specialised Products from Amino Acids
• Glycine
• 1) Formation of Purine ring – Glycine is utilized for carbons 4 & 5 and
position 7 of nitrogen
• 2) Formation of the tripeptide Glutathione ( gamma glutamyl cysteinyl
glycine)
• 3) Synthesis of Heme –Glycine with Succinyl CoA forms delta Amino
Levulenate which is a precursor of Heme synthesis.
• 4) Biosynthesis of Creatine – This is a high energy compound in the
form of phosphocreatine present in muscles. 3 Amino acids required
are Glycine, Arginine and Methionine

16. Arginine
• 1) Production of Ornithine and liberation of Urea in the Urea cycle
when Arginine is cleaved by enzyme Arginase
• 2)Formation of Nitric Oxide (NO)- Arginine is the substrate for
formation of NO . This NO acts as a mediator for several biological
functions. It acts as a vasodilator, a neurotransmitter and promotes
synthesis of cGMP.
• Synthesis of Creatine

17. Methionine
• 1) Used in synthesis of S- Adenosyl Methionine (SAM). This is a highly
reactive compound and there will be transfer of methyl groups by
enzymes the methyl transferases. After the methyl group is
transferred to an acceptor molecule by trans methylation reactions
SAM gets converted to S- Adenosyl Homocysteine
• 2) Homocysteine formed from Methionine is a precursor of Cysteine
another sulphur containing AA
• 3) Synthesis of Creatine (SAM)

18. Phenylalanine and Tyrosine
• 1) Phenyl alanine an essential AA gets converted to Tyrosine a non
essential AA, so besides being incorporated in proteins the only
function of Phenylalanine is conversion to Tyrosine by Phenylalanine
hydroxylase.
• 2)Tyrosine is the precursor of Melanin the colour pigment . The
enzyme is Tyrosinase.
• 3) Thyroid hormones T3 & T4 are synthesized from Tyrosine residues
and activated iodine
• Tyrosine is the precursor of Catecholamines – Dopamine,
Norepinephrine and Epinephrine

19. • Norepinephrine & Epinephrine regulate Carbohydrate and Lipid
metabolism and they stimulate the degradation of Triglycerol and
Glycogen.
• They can increase blood pressure
• Dopamine and Norepinephrine act as neurotransmitters in the brain.