Urea cycleUrea cycle

DefinitionDefinition

The The urea cycleurea cycle (also known as the (also known as the ornithine cycleornithine cycle) is a cycle of ) is a cycle of biochemical reactions occurring in reactions occurring in many animals that produces many animals that produces urea ( (NH2)22)2CO from from ammonia (NH3) (NH3)

FunctionFunction Organisms that cannot easily and Organisms that cannot easily and

quickly remove ammonia usually quickly remove ammonia usually have to convert it to some other have to convert it to some other substance, like urea or substance, like urea or uric acid,uric acid, which are much less toxic.which are much less toxic.

Insufficiency of the urea cycle occurs Insufficiency of the urea cycle occurs in some genetic disorders (inborn in some genetic disorders (inborn errors of metabolism), and in errors of metabolism), and in liver liver failure. failure.

• Urea is less toxic than ammonia.Urea is less toxic than ammonia.

• The The Urea CycleUrea Cycle occurs mainly in occurs mainly in liverliver. .

• The 2 nitrogen atoms of urea enter The 2 nitrogen atoms of urea enter the Urea Cycle as the Urea Cycle as NHNH33 (produced (produced mainly via Glutamate mainly via Glutamate Dehydrogenase) and as the aminoDehydrogenase) and as the amino NN of aspartateof aspartate. .

• The NHThe NH33 and HCO and HCO33 (carbonyl C) that (carbonyl C) that

will be part of urea are incorporated will be part of urea are incorporated first into first into carbamoyl phosphatecarbamoyl phosphate. .

H 2 N C

O

N H 2

u r e a

Urea cycleUrea cycle Ammonia is toxicAmmonia is toxic

Readily ionises to ammonium Readily ionises to ammonium

ion NHion NH44++

NHNH44+ + converted to urea in liver converted to urea in liver

(urea cycle)(urea cycle)

Urea contains 2 x NHUrea contains 2 x NH22

One from NHOne from NH44++

One from aspartate One from aspartate

Urea excreted in urineUrea excreted in urine

Urea CycleUrea Cycle• Enzymes in Enzymes in

mitochondriamitochondria: : 1.1. Ornithine Ornithine Trans-Trans- carbamylasecarbamylase

Enzymes in Enzymes in cytosolcytosol::

2.2. Arginino- Arginino- SuccinateSuccinate SynthaseSynthase3.3. Arginino- Arginino- succinasesuccinase4.4. Arginase. Arginase.

H2N C OPO32

O

CH2

CH2

CH2

HC

COO

NH3+

NH3+

CH2

CH2

CH2

HC

COO

NH3+

NH

CO NH2

COO

CH2

HC

COO

NH2

CH2

CH2

CH2

HC

COO

NH3+

NH

C NH2+

COO

CH2

HC

COO

HN

AMP + PPi

ATP

CH2

CH2

CH2

HC

COO

NH3+

NH

C

NH2+H2N

COO

HC

CH

COO

C NH2H2N

O H2O

Pi

ornithine

urea

citrulline

aspartate

arginino- succinate

fumarate

arginine

carbamoyl phosphate

Urea Cycle

1

2

3

4

BY:BY:

Abdulrhman Mohammed Twhari.Abdulrhman Mohammed Twhari.

Ebrahim MohammedEbrahim Mohammed DaghririDaghriri