amino acids

1. BioCHEMISTRY
b.Pharma 2nd semester unit-3rd
Mr. Bulet Kumar Gupta
Assistant Professor
Sai College of Pharmacy, Mau

2. METABOLISM OF AMINO ACIDS
The amino acids undergo certain common reactions like transamination
followed by deamination for the liberation of ammonia. The amino
group of the amino acids is utilized for the formation of urea which is an
excretory end product of protein metabolism. The carbon skeleton of
the amino acids is first converted to keto acids (by transamination)
which meet one or more of the following fates.
1. Utilized to generate energy.
2. Used for the synthesis of glucose.
3. Diverted for the formation of fat or ketone bodies.
4. Involved in the production of non-essential amino acids.

4. TRANSAMINATION
The transfer of an amino ( NH2) group from an amino acid to a keto acid
is known as transamination. This process involves the interconversion of
a pair of amino acids and a pair of keto acids, catalysed by a group of
enzymes called transaminases.

5. Salient features of transamination
1. All transaminases require pyridoxal phosphate (PLP), a coenzyme
derived from vitamin B6.
2. Specific transaminases exist for each pair of amino and keto acids.
However, only two— namely, aspartate transaminase and alanine
transaminase—make a significant contribution for transamination.
3. There is no free NH3 liberated, only the transfer of amino group
occurs.
4. Transamination is reversible.
5. Transamination is very important for the redistribution of amino
groups and production of non-essential amino acids, as per the
requirement of the cell.

6. DEAMINATION
The removal of amino group from the amino acids as NH3 is
deamination. Transamination involves only the shuffling of amino
groups among the amino acids. On the other hand, deamination results
in the liberation of ammonia for urea synthesis. Simultaneously, the
carbon skeleton of amino acids is converted to keto acids. Deamination
may be either oxidative or non-oxidative. Although transamination and
deamination are separately discussed, they occur simultaneously, often
involving glutamate as the central molecule. For this reason, some
authors use the term transdeamination while describing the reactions of
transamination and deamination, particularly involving glutamate

7. I. Oxidative deamination
Oxidative deamination is the liberation of free ammonia from the
amino group of amino acids coupled with oxidation. This takes place
mostly in liver and kidney. The purpose of oxidative deamination is
to provide NH3 for urea synthesis and D-keto acids for a variety of
reactions, including energy generation.

8. II. Non-oxidative deamination
Some of the amino acids can be deaminated to liberate NH3 without
undergoing oxidation
(a) Amino acid dehydrases : Serine, threonine and homoserine are the
hydroxy amino acids. They undergo non-oxidative deamination
catalysed by PLP-dependent dehydrases.
(b) Amino acid desulfhydrases : The sulfur amino acids, namely cysteine
and homocysteine, undergo deamination coupled with desulfhydration
to give keto acids.

9. (c) Deamination of histidine : The enzyme histidase acts on histidine to
liberate NH3 by a non-oxidative deamination process.

10. UREA CYCLE
Urea is the end product of protein metabolism (amino acid metabolism).
The nitrogen of amino acids, converted to ammonia is toxic to the body.
It is converted to urea and detoxified. As such, urea accounts for 80-90%
of the nitrogen containing substances excreted in urine. Urea is
synthesized in liver and transported to kidneys for excretion in urine.
Urea cycle is the first metabolic cycle that was elucidated by Hans Krebs
and Kurt Henseleit (1932), hence it is known as Krebs-Henseleit cycle.
Urea has two amino ( NH2) groups, one derived from NH3 and the other
from aspartate. Carbon atom is supplied by CO2. Urea synthesis is a five-
step cyclic process, with five distinct enzymes. The first two enzymes are
present in mitochondria while the rest are localized in cytosol.

11. 1. Synthesis of Carbamoyl Phosphate
2. Formation of Citrulline
3. Synthesis of Arginosuccinate
4. Cleavage of arginosuccinate
5. Formation of Urea

12. Metabolic disorders of urea cycle
Metabolic defects associated with each of the five enzymes of urea cycle
have been reported. All the disorders invariably lead to a build-up in
blood ammonia (hyperammonemia), leading to toxicity. Other
metabolites of urea cycle also accumulate which, however, depends on
the specific enzyme defect. The clinical symptoms associated with
defect in urea cycle enzymes include vomiting, lethargy, irritability,
ataxia and mental retardation.
Blood urea—clinical importance
In healthy people, the normal blood
urea concentration is 10-40 mg/dl.

13. CATABOLISM OF PHENYLALANINE AND TYROSINE AND ASSOCIATED
METABOLIC DISORDERS
The aromatic amino acids phenylalanine (Phe) and tyrosine (Tyr) have
almost similar structure.
It is important to consume foods high in phenylalanine.
Consuming tyrosine-rich foods, on the other hand, is not required.
After being incorporated into proteins, phenylalanine has no other
function than to convert to tyrosine.
Tyrosine can thus reduce the body's need for phenylalanine. Tyrosine's
sparing action on phenylalanine is known as the “sparing action.'

14. Catabolism of phenylalanine and tyrosine.
Both phenylalanine and tyrosine metabolism are interconnected and are
degraded in the liver by the same pathway.
The p-hydroxyphenylpyruvate is produced by transamination of
tyrosine.
Enzyme: Tyrosine transaminase.
p hydroxyphenylpyruvate is decarboxylated and its phenyl ring is
hydroxylated to form homogentisate.
Ascorbic acid is needed for this reaction.
The benzene ring is removed by homogentisate oxidase, resulting in the
formation of 4-Maleylacetoacetate. To break an aromatic ring,
molecular oxygen is required.

15. Maleylacetoacetate is isomerized to 4-fumarylacetoacetate;
Enzyme: maleylacetoacetate isomerase.
Fumarylacetoacetate is hydrolyzed to form Fumarate and acetoacetate.
Enzyme: fumarylacetoacetate hydrolase.
Fumarate is an intermediate in the citric acid cycle and hence
gluconeogenic.
Acetoacetate, which is a ketone body.
Hence, tyrosine and phenylalanine are both ketogenic and glucogenic
Metabolic disorders:
1- Phenylketonuria 2- Albinism
3- Alkaptonuria 4- Tyrosinemia.

16. Phenylketonuria
Phenylketonuria (PKU) is an hereditary metabolic disorder that results
in a high level of phenylalanine in the blood.
The body can accumulate very high levels of phenylalanine which may
prove toxic without treatment, resulting in mental retardation and other
serious complications.
Pregnant women who consume
a lot of phenylalanine are more
likely to have babies with
mental retardation, heart
problems, and small heads
(microcephaly).

17. ALBINISM
Both parents carrying the albinism gene have a chance of passing the
albinism gene to their child.
The cause of albinism is a defect in one of several genes involved in
producing and distributing melanin, the pigment responsible for skin,
eyes, and hair coloration.
Melanin may not be produced or may be produced
in very small amounts due to the defect.
The gene for albinism is inherited from both parents, so a child must
have both parents carry the gene.
Parents who carry the albinism gene but don't have symptoms are
typically carriers of the condition.

18. Alkaptonuria
It's a very rare and hereditary disorder, which causes kidney problems.
Caused due to lesser production or total lack of enzyme homogentisic
dioxygenase (HGD).
Toxic substances such as homogentisic acid are broken down by this
enzyme.
Results in high levels of homogentisic acid.
Symptoms of Alkaptonuria
•There are dark spots on your eye's sclera (white)
•The cartilage in your ears has thickened and darkened
•Discoloration of your skin, especially in the sweat gland area, that is
blue speckled

19. •Sweat of a dark color or stains of sweat
•Earwax that is black in color
•A urinary stone and a prostate stone
•Knee and hip arthritis (especially)
•Heart problems can also occur as a result of alkaptonuria.

20. Tyrosinemia
The body lacks the enzyme [fumarylacetoacetate hydrolase (FAH).
A person with tyrosinemia breaks down protein in their bodies in an
abnormal way, allowing toxic breakdown products of tyrosine to build
up in the body.
There is progressive liver damage as well as kidney damage.
It's a hereditary disorder.

21. Synthesis and significance of biological substances: Serotonin,
Melatonin, Catecholamines.
Synthesis and Significance of 5-HT:
Also called “Serotonin”.
There are three main types of cells that store serotonin (5-HT)--
Blood platelets
Neurons in the brain and the intestinal myenteric plexus,
Mucosa of the gastrointestinal tract contains enterochromaffin
cells.
The enterochromaffin cells and serotonergic neurons produce serotonin
from L-tryptophan, Platelets uptake the serotonin from blood.

22. Functions of Serotonin
1. Mood elevator.
2. Involved in bone
metabolism.
3. Involved in cardiovascular
health.
4. Involved in eye health.
5. Involved in blood
clotting.
6. Involved in neurological
disorders.

23. Melatonin
Secreted by “Pineal Gland” and regulates sleep.
Secretion depends on light, secreted in dim light i.e. during night, effects
are minimum during day.
Synthesized in the body from a similar pathway of Serotonin.
Functions:
1. Melatonin functions can delay aging processes.
2. Scavenging free radicals,
3. Stabilizing biological rhythms,
4. Stimulates the immune system.
5. Decreases susceptibility to stress.
6. Sleep quality and mood are improved.

24. Catecholamines
The substances containing catechol nuclei in their chemical structure
are called “Catecholamines”
Following are important catecholamines in the body,
•Dopamine.
•Adrenaline.
•Noradrenaline.
Tyrosine is the precursor for the synthesis of catecholamines.
The conversion of tyrosine to catecholamines occurs in adrenal
medulla and central nervous system.

25. Synthesis of Catecholamines:

26. Functions of catecholamines
•Nor epinephrine and epinephrine regulate carbohydrate and lipid
metabolisms.
•They stimulate the degradation of triacylglycerol and glycogen.
•They cause an increase in blood Pressure.
•Dopamine and nor epinephrine serve as neurotransmitters in the brain
and autonomic nervous system.
•Neurotransmitter dopamine plays a role in the brain. Striving, focusing,
and finding something interesting rely on it.
•It is associated with pleasure.

27. Catabolism of Heme
Heme is the non-protein part of Hemoglobin.
Heme is the most important porphyrin containing compound.
Porphyrins are cyclic compounds composed of 4 pyrrole rings held
together by methenyl(=CH) bridges.
lt is synthesized in the liver and bone marrow.
Heme oxygenase utilizes NADPH and 02 and cleaves the methenyl
bridges between the two pyrrole rings (A and B) to form biliverdin.
Simultaneously, ferrous iron (Fe2+) is oxidized to ferric form (Fe3+) and
released.The products of heme oxygenase reaction are biliverdin (a
green pigment), Fe3+and carbon monoxide (CO).

28. Biliverdin's methenyl bridges (between the pyrrole rings C and D) are
reduced to form bilirubin (yellow pigment). This reaction is catalysed by
biliverdin reductase.
Transport of bilirubin to liver: Bilirubin is lipophilic and therefore
insoluble in aqueous solution. So it is non covalently bound to albumin
and is transported.
Hyperbilirubinemia and Jaundice
Hyperbilirubinemia represent the increased concentration of serum
bilirubin. Jaundice is a clinical condition characterized by yellow colour
of the white of the eyes (sclerae) and skin.
This is due to the elevated serum bilirubin level, usually beyond 2 mg/dl
(normal < 1 mg/dl).

29. Hemolytic jaundice: is associated with increased hemolysis of
erythrocytes In hemolytic jaundice, more bilirubin is excreted into the
bile.
Hemolytic jaundice is characterized by:
1. Elevation in the serum unconjugated bilirubin.
2. Increased excretion of urobilinogen in urine.
3. Dark brown colour of feces
Hepatic (hepatocellular) jaundice is caused by dysfunction of the Iiver
due to damage to the parenchymal cells.
Hepatic jaundice is characterized by
1. Increased levels of conjugated and unconjugated bilirubin in the
serum.

30. 2. Dark coloured urine.
3. lncreased activities of alanine transaminase (SGPT) and aspartate
transaminase (SCOT) released into circulation due to damage to
hepatocytes.
4. The patients pass pale, clay colored stools.
5. Nausea and anorexia (loss of appetite).