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UREA CYCLE

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UREA CYCLE ,Regulation and Overall stoichiometry of the urea cycle, (Clinical hint) Hyperammonemia

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The toxic free ammonia molecule released from oxidative deamination reaction by glutamate
dehydrogenase enzyme is transported from peripheral tissues through blood to hepatocytes
by 2 mechanisms explained in the previous lecture. Now ammonia in hepatocytes and ready to
be converted into urea by UREA CYCLE the main topic to be discussed in this lecture.

UREA CYCLE:
❖ As explained before the free ammonia
produced from oxidative deamination of
Glutamate which is converted into urea-
less toxic molecule- in liver (hepatocytes).
Urea can be safely transported through
blood to kidneys to be excreted in urine.
Accordingly, urea is the major disposal
form of amino groups derived from AAs
(urea accounts for about 90% of the
nitrogen containing compounds of urine).

❖ Urea cycle and TCA cycle are similar in
principle, both need a starting material
→starting material interacts with the last
intermediate in the cycle to initiate series
of reactions. Also, none of the
intermediates involved are produced or consumed unless these intermediates are used
in other biochemical pathways. Urea cycle is different from TCA cycle that urea cycle
consumes energy in the form of ATP to get rid of the toxic ammonia, occur only in
hepatocytes and all steps of this cycle are irreversible. However, TCA cycle is efficient in
producing energy, occur in all tissues and few steps of TCA are irreversible.


❖ Reactions of urea cycle occur in two places in hepatocytes: 1) cytosol. 2) mitochondria.

❖ Reactions of urea cycle occur in two phases:
The first phase: building up intermediate from smaller ones.
The second phase: breaking down intermediates into smaller ones.

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