generation of metabolic energy A mino acids, through their
oxidative degradation, make a significant contribution to the
generation of metabolic energy.
Slide 3
In animals, amino acids undergo oxidative degradation in three
different metabolic circumstances: a.During the normal synthesis
and degradation of cellular proteins, some amino acids that are
released from protein breakdown and are not needed for new protein
synthesis undergo oxidative degradation. b. When a diet is rich in
protein and the ingested amino acids exceed the bodys needs for
protein synthesis, the surplus is catabolized; amino acids cannot
be stored. c. During starvation, when carbohydrates are either
unavailable or not properly utilized, cellular proteins are used as
fuel.
Slide 4
Under all these metabolic conditions, amino acids lose their
amino groups to form -keto acids, the carbon skeletons of amino
acids. The -keto acids undergo oxidation to CO 2 and H 2 O or,
often more importantly, provide three- and four-carbon units that
can be converted by gluconeogenesis into glucose, the fuel for
brain, skeletal muscle, and other tissues.
Slide 5
In most tissues, uses glutamine synthetase to combine ammonia
(NH 3 ) with glutamate to form glutaminea nontoxic transport form
of ammonia. The glutamine is transported in the blood to the liver
where it is cleaved by glutaminase to produce glutamate and free
ammonia (see p. 256). Transport of ammonia to the liver
Slide 6
Slide 7
Most terrestrial animals are ureotelic, excreting amino
nitrogen in the form of urea. Birds and reptiles are uricotelic,
excreting amino nitrogen as uric acid. Most aquatic species, such
as the bony fishes, are ammonotelic, excreting amino nitrogen as
ammonia. In ureotelic organisms, the ammonia deposited in the
mitochondria of hepatocytes is converted to urea in the Urea Cycle.
occurs exclusively in the liver. This pathway was discovered in
1932 by Hans Krebs and a medical student associate, Kurt
Henseleit.
Slide 8
Urea cycle
Slide 9
The urea cycle begins inside liver mitochondria, but three of
the subsequent steps take place in the cytosol; the cycle thus
spans two cellular compartments. The first amino group to enter the
urea cycle is derived from ammonia in the mitochondrial matrix. The
liver also receives some ammonia via the portal vein from the
intestine, from the bacterial oxidation of amino acids. The NH + 4
generated in liver mitochondria is immediately used, together with
CO 2 (as HCO 3 ) to form carbamoyl phosphate in the matrix. (ATP-
dependent reaction; carbamoyl phosphate synthetase I)
Slide 10
The carbamoyl phosphate, which functions as an activated
carbamoyl group donor, now enters the urea cycle. Four enzymatic
steps: Step1: Formation of citrulline from ornithine and carbamoyl
phosphate (entry of the first amino group); the citrulline passes
into the cytosol. Step2: Formation of argininosuccinate through a
citrullyl-AMP intermediate (entry of the second amino group).
Slide 11
Step 3: Formation of arginine from argininosuccinate; this
reaction releases fumarate, which enters the citric acid cycle.
Step 4: Formation of urea; this reaction also regenerates,
ornithine.
Slide 12
Slide 13
Slide 14
The second amino group now enters from aspartate (generated in
mitochondria and transported into the cytosol) by a condensation
reaction between the amino group of aspartate and the ureido
(carbonyl) group of citrulline, forming argininosuccinate. This
cytosolic reaction, catalyzed by argininosuccinate synthetase,
requires ATP and proceeds through a. citrullyl-AMP
intermediate.
Slide 15
The argininosuccinate is then cleaved by argininosuccinase, to
form free arginine and fumarate. This is the only reversible step
in the urea cycle The cytosolic enzyme arginase cleaves arginine to
yield urea and ornithine. (Step4) Ornithine is transported into the
mitochondrion to initiate another round of the urea cycle.