Scribd
Upload
26 views3 pages

General Protein Metabolism Full (2nd Weeks) 2021

Uploaded by

Mohamed Abouzaid
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOC, PDF, TXT or read online on Scribd
26 views3 pages

General Protein Metabolism Full (2nd Weeks) 2021

Uploaded by

Mohamed Abouzaid
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOC, PDF, TXT or read online on Scribd
You are on page 1/ 3

GENERAL ASPECTS OF PROTEIN METABOLISM

Urea Cycle

Definition and Importance


This is the principal pathway of disposal of ammonia resulting from the deamination of
amino acids, in a neutral non-toxic form. Urea is an end product that is excreted in urine.
Site
Urea formation occurs only in the liver as arginase is present only in the liver . The first 2
reactions occur in the mitochondria and all subsequent reactions occur in the cytosol.
Steps
The overall reactions of urea cycle are as follows:
Aspartate + NH3 + CO2 + 3ATP  Urea + fumarate + 2ADP + 2 Pi +AMP + PPi

The different steps include


1-Free ammonium ion and bicarbonate (CO2) are condensed, at the expense of 2 ATP, to form
carbamoyl phosphate. The reaction is catalyzed by carbamoyl phosphate synthetase I (CPSI),
which occurs in the mitochondrial matrix, and uses ammonia as a nitrogen donor. It is absolutely
dependent on N-acetylglutamate for its activity.
[N.B. Carbamoyl phosphate synthetase II (CPSII): It is another enzyme with similar activity. It
is a cytosolic enzyme and uses the amide group of glutamine for pyrimidine synthesis, and not
affected by N-acetylglutamate].
2- Formation of citrulline is catalyzed by ornithine transcarbamoylase in the mitochondrial
matrix. Citrulline is transported out of the mitochondria to the cytosol (in exchange with
ornithine), where the other reactions of the urea cycle occur.
3- Formation of argininosuccinate is catalyzed by argininosuccinate synthetase, which requires
hydrolysis of ATP to AMP and PPi (the equivalent of hydrolysis of two molecules of ATP).
4- Cleavage of argininosuccinate by argininosuccinate lyase produces fumarate and arginine.
5- Arginine is cleaved by arginase to ornithine and urea. Ornithine returns back to the
mitochondrial matrix for another turn of the cycle.
Reactions of Urea Cycle
NH3 + CO2 + ATP
ATP
+ Carbamoyl phosphate
N-acetyl-glutamate synthetase I
ADP + Pi
ADP

O
NH2 – C – O ~ P

Carbamoyl phosphate
NH2 – R
Ornithine Ornithine
transcarbamoylase
Pi
O
Mitochondria Citrulline H2N – C – NH – R

Ornithine-Citrulline Antiporter Mitochondrial Membrane

Cytosol ATP
α-KG CH2-COOH Arginino
succinate
AST H2NCH-COOH synthetase
Glu PLP AMP + PPi
Aspartate
Oxaloacetate
NH
+
CH2-COOH
NADH,H
Malate R – HN – C – HN – CH-COOH
dehydrogenase Argininosuccinate
+
NAD
Argininosuccinase
L-Malate
(Argininosuccinate lyase)

HC-COOH NH
Fumarase HOOC-CH
Fumarate H2N – C – NH – R
H 2O
H2O Arginine
NH2 – R Arginase
Ornithine
O

H2N – C – NH2 Urea

Regulation of Urea Cycle


1- N-acetylglutamate is an essential activator for carbamoyl phosphate synthetase rate-limiting
step in the urea cycle. N-Acetylglutamate is synthesized from acetyl CoA and glutamate, in
a reaction for which arginine is an activator. Therefore, the intrahepatic concentration of N-
acetylglutamate increases after ingestion of a protein-rich meal, which provides both the
substrate (glutamate) and the regulator of N-acetylglutamate synthesis. This leads to an
increased rate of urea synthesis

Regulation of Activity of CPSI


Arginine CO2 + NH3
2 ATP
+ CoA
Glutamate + Acetyl-CoA N-Acetylglutamate + CPSI
N-Acetyglutamate
synthase 2 ADP + Pi
O
Carbamoyl phosphate NH2 – C – O ~ P

2- Factors affecting levels of urea cycle enzymes:


- High protein diet: major changes in diet can increase the concentration of individual urea
cycle enzymes 10 to 20 folds.
- Administration of the protein catabolic hormones increases the concentration of urea
cycle enzymes.
- Starvation elevates urea cycle enzyme levels to cope with the increased production of
ammonia that accompanies enhanced degradation of proteins.

You might also like