1. Proteins undergo periodic degradation in the body to form what?

2. What are the sources of ammonia?

3. What happens to ammonia in the body (fate of ammonia)?
4. What is the overview of production of ammonia from different sources?
5. What is ammonia toxicity (hyperammonemia)?
6. How does the brain handle ammonia?
7. What is the clinic implication of ammonia intoxication?
8. What are the symptoms of ammonia intoxication?
9. How is ammonia transported?
10. What is the first mechanism for ammonia transport?
11. What is the second mechanism for ammonia transport?
12. What is the glucose alanine cycle?
13. How does transamination occur?
14. How does aminotransferases occur?
15. What is the mechanism of transamination?
16. What is the biological significance of transamination?
17. What is the diagnostic significance of transamination?
18. What is aspartate aminotransferase (AST)?
19. What is alanine aminotransferase (ALT)?
20. What is the fate of glutamate in urea cycle?
21. What is the central role of glutamate in nitrogen disposal?
22. What is the role of liver and kidneys in pH regulation?
23. What is the minor pathways of deamination?
24. Name different non oxidative deamination synthesis?
25. What is the urea cycle (krebs-henseleit cycle)
26. What is the energetic of the urea cycle?
27. What is the regulation of the urea cycle?
28. What is the biological significance of the urea synthesis?
29. What are the inherited disorders of the urea cycle?
30. What is the treatment for inherited disorders of urea cycle?
31.
1. Amino acids
2. Transamination of amino acids, deamination of amino acids, from glutamine by the
action of glutaminase, by the action of intestinal bacteria, degradation of biogenic
amines, breakdown of purine and pyrimidines.
3. Biosynthesis of glutamate from ammonia and a-ketoglutarate, biosynthesis of non-
essential amino acids, biosynthesis of glutamine by the action of glutamine synthetase,
traces of excreted in urine as NH+4, major portion converted to urea in the liver and
excreted in the urine.
4.

5. The level of ammonia in the blood must be kept very low, (10-20 microgram/dL)
(elevated levels of ammonia is toxic to the CNS). Ammonia should be moved from
peripheral tissues to the liver for ultimate disposal as urea. In liver cirrhosis, development
of collateral links between the portal and systemic circulation occurs which raise the
ammonia levels in systemic circulation to toxic levels.
6. When the liver fails to regulate ammonia concentrations, the brain, devoid of a urea
cycle, relies solely on the amidation of glutamate to glutamine through glutamine
synthetase, to efficiently clear ammonia.
7. Excess ammonia is rapidly converted to glutamine-by glutamine synthestase. This
depletes glutamate levels in brain which is a precursor for the synthesis of GABA. This
results in reduced levels of this inhibitory neurotransmitter. To compensate for glutamate,
a-ketoglutarate is used, which consequently depresses TCA and thus deprives brain cells
of energy. Excess glutamine is exchanged with tryptophan, a precursor of serotonin,
causing hyperexcitation.
8. Symptoms of ammonia toxicity include blurred vision, slurred speech, confusion,
vomiting, tremors and cerebral edema resulting in coma and death.
9. NH3 is transported from peripheral tissues to liver for conversion to urea. There is two
mechanisms for ammonia transport which are by glutamine synthesase that combines
NH3 with Glu to form Gln and by transamination of pyruvate to form alanine- glucose-
alanine cycle (cahill cycle)
10. Glutamine synthetases combine NH3 with Glu to form Gln and it is found in most
tissues, requires energy, a nontoxic transport form of ammonia, the resulting glutamine is
transported in the blood to the liver to be cleaved by glutaminase to produce glutamate
and free ammonia.
11. Transamination of pyruvate to form alanine- glucose-alanine cycle (cahill cycle).
Primarily in muscles- alanine is transported by the blood to the liver to be converted to
pyruvate by transamination. Pyruvate can be used in gluconeogenesis.
12. The glucose-alanine cycle is used primarily as a mechanism for skeletal muscle to
eliminate nitrogen while replenishing its energy supply. Role of muscle in wasting
conditions, starvation or in anorexia nervosa.

13. Transamination, oxidative deamination, ammonia transport, reactions of urea cycle

14. The funneling of amino groups to glutamate. In transamination, transfer of amino groups
from one carbon skeleton to another is catalyzed by a family of readily reversible
enzymes called aminotransferases (also called transaminases). These enzymes are found
in the cytosol and mitochondria of cells throughout the body.

All aminotransferases require the coenzyme pyridoxal phosphate (a derivative of vitamin

B6). All amino acids, except for lysine and threonine, participates in transamination at
some point in their catabolism.
15. Aminotransferases act by transferring the amino group of an amino acid substrate
(glutamate) to the pyridoxal part of the coenzyme to generate pyridoxamine phosphate.
The amino acid substrate glutamate is thus converted to an a-keto acid product (a-
ketoglutarate). The pyridoxamine form of the coenzyme then reacts with an a-keto acid
substrate (oxaloacetate) to form an amino acid product (aspartate), at the same time
regeneraing the original aldehyde form of the coenzyme. Transamination reactions are
reversible allowing the reaction to function in both amino acid degradation through
 removal of a-amino grouos and biosynthesis of nonessential amino acids through addition
of amino groups to the carbon skeletons of a-keto acids.

16. Synthesis of non essential amino acids, degradation of amino acids, transport of NH2,
play a role in anabolic and catabolic processes.
17. Aminotransferases are normally intracellular enzymes, with the low levels found in the
plasma representing the release of celular contents during normal cell turnover. Elevated
plasma levels of aminotransferases indicate damage to cells rich in these enzymes. For
example, physical trauma or a disease process can cause cell lysis, resulting in releasee of
intracellular enzyme into the blood. Two aminotransfersases, AST and ALT, are of
diagnostic value when they are found in the plasma.
18. AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas,
lungs, leukocytes, and erythrocytes. Normal serum activity is 0-41IU/L. the concentration
of the enzyme is very high in myocardium. AST levels are elevated in hepatic diseases
and non hepatic diseases such as cardiac or muscle disorders.

19. ALT is found primarily in the liver. The normal serum activity ranges between 0-45 IU/L.
ALT is elevated in hepatic diseases that result in extensive cell necrosis like severe viral
hepatitis, toxic injury and obstructive liver disease. Measurement of both AST and ALT
are useful in determining the course of liver damage.
20. Glutamate produced by tansamination can be oxidatively deaminated to release NH3 or
used as an ammino group donor in the synthesis of nonessential amino acids.
21. Glutamate acts as a reservior of amino groups of most amino acids. All the amino
nitrogen from amino acids that undergo transamination can be concentrated in glutamate.
Conversion of a-amino nitrogen to ammonia by the converted action of aminotransferases
(AST) and (ALT) and glutamate dehydrogenase (GDH) is often termed
‘transdeamination”. Liver GDH activity is allosterically inhibited by ATP, GTP, and
NADH, and is activated by ADP. The GDH reaction is freely reversible, and functions in
amino acid biosynthesis.
22. Major reactions that involve the regulation of plasma pH as well as the level of
circulating ammonium ion (NH4) involve the hepatic and renal enzymes glutamate
dehydrogenase (GDH), glutamine synthtase (GS) and glutaminase. The liver
compartmentalizes GS and glutaminase in order to control the flow of ammonia into
glutamine or urea. Under acidotic conditions the liver incorporates NH4 into glutamine
via the GS reaction. The glutamine then enters the circulation. In fact, glutamine is the
major amino acid of the circulation, and its role is to ferry NH4 to and from various
tissues in a nontoxic from. In the proximal tubule of the kidneys, glutamine, is
hydrolyzed by glutaminase (yielding glutamate) releasing ammonia. Another mole of
ammonia is released through the action of glutamate dehydrogenase acting on the
glutamate derived from the glutaminase reaction.
Within the proximal tubule cells, the ammonia ionizes with a hydrogen ion yielding
ammonium ion, NH4. The net effect is that a single mole of glutamine, taken up by the
proximal tubule, generates two moles of NH4 effectively reducing the circulating
concentration of H+ by two moles resulting in an increase in the pH. This process of
coordination between the liver and kidney is crucial to overall regulation of acid base
balance. Within the proximal tubule of the kidney, the release of ammonia from
glutamine and the generation of NH4 is referred to as renal ammonia genesis.
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