proteiin_metabolism_

1. Amino acids and Proteins
Metabolism
Presented by:
Mashair Elzubair Ezeldein

2. • Quantitatively, proteins are the most important
group of endogenous macromolecules. Aperson
weighing 70 kg contains about 10 kg protein, with
most of it located in muscle.
• Carbohydrates, lipids and proteins are energy-
giving nutrients Hence they are known as
proximate principles of diet
• Carbohydrates and lipids are used mainly as
energy source

3. • Provision of energy is not the primary
purpose of amino acid metabolism
Amino acids are used mainly to:
• Synthesize various proteins Form some
specialized non-protein products

4. • Amino acids can be used as a source
of energy if:
Availability of carbohydrates and lipids is low
Availability of amino acids exceeds their
requirement.
In plasma as well as in tissues, there is an
amino acid pool
Amino acids are continuously added to
and removed from the pool

5. Amino acids are obtained from:
• Digestion of dietary proteins
• Breakdown of body proteins
• Endogenous synthesis
• Amino acids are used for:
• Synthesis of body proteins
• Synthesis of non-protein
• specialized products
• Provision of energy

8. Nitrogen balance
• Proteins are the main nitrogenous
constituent of our diet
• Proteins are broken down into amino
Acids, Catabolism of amino acids results in
the release of their amino groups in the
form of ammonia. Small amounts of nitrogen
are also excreted in the form of uric acid,
creatinine, and ammonium ion

9. • In human beings and other mammals,
ammonia is converted into urea which
is excreted in urine
• Urea is the main nitrogenous compound
excreted from the body
• Thus, nitrogen is taken in mostly as
proteins and excreted mainly as urea
• The relative intake and excretion of
nitrogen is known as the nitrogen
balance

10. Nitrogen equilibrium
• In healthy adults, nitrogen excretion equals
nitrogen intake
The person is said to be in nitrogen Equilibrium
• Positive nitrogen balance
• In growing age, amino acids are used to form
tissue proteins
Therefore, nitrogen excretion is less than the
intake The individual is said to be in a positive
nitrogen balance

11. Negative nitrogen balance
• In starvation and wasting diseases(burns,
trauma, stress and cancer), there is
excessive breakdown of body proteins
• Nitrogen excretion exceeds the intake
The individual is said to be in negative
nitrogen balance.

12. • Essential and non-essential amino
acids
• Proteins are synthesized from twenty
L-amino acids (standard amino acids) in
living organisms
• All these amino acids are equally
important for protein synthesis

13. • However, the presence of all these amino
acids in diet is not imperative
• Some of these can be synthesized in
human beings
• Amino acids that cannot be synthesized by
human beings are nutritionally essential
Their presence in diet is imperative

14. • Two amino acids, arginine and histidine,
are said to be semi-essential
Their endogenous synthesis cannot meet
the requirements in growing age
• The remaining amino acids can be
synthesized in adequate amounts
• They are considered to be nutritionally
non-essential or dispensable

16. • Synthesis of non- and semi-essential amino
acids
• These amino acids can be synthesized in
human beings from:
Amphibolic intermediates
• Some other amino acids

17. • Glycine from serine: catalyze by serine
hydroxy-methyltransferase enzyme

18. • Alanine from pyruvate: Transamination of
pyruvate forms alanine catalyzed by
Alanine Transaminase.

19. • Serine from 3-phosphoglycerate:Catalyze
by dehydrogenase & transaminase

20. • Aspartate from oxaloacetate:
Transamination of oxaloacetate forms
aspartate catalyzed by Aspartate Transaminase.
•

21. • Synthesis of glutamate from α-
ketoglutarate:The reaction catalyze by
glutamate dehydrogenase .

23. • Inborn errors of metabolism occur when
some enzyme involved in metabolism is
abnormal
The abnormality occurs due to a mutation
in gene encoding the enzyme
• The affected enzyme may be absent or
deficient

25. • The clinical abnormalities may occur
due to:
Decreased synthesis of products
Accumulation of intermediates, Formation of
alternate metabolite
Many disorders result in neurological
abnormalities and mental retardation
Early diagnosis and treatment can prevent
neurological abnormalities

26. • Generally, the treatment comprises
restricted intake or exclusion of the affected
amino acid from the diet

27. Catabolism of amino acids
• Catabolism of amino acids comprises
• catabolism of their:
• Amino groupsand Carbon skeletons
• Carbon skeletons of different amino acids
have different fates
• The fate of their amino groups is the
sameThe amino groups of amino acids
areremoved as ammonia
•

28. • Since ammonia is very toxic, it has to be
converted into a non-toxic metabolite
• In ureotelic organisms, e.g. mammals,
ammonia is converted into urea
Though amino acids are catabolized in
several tissues, urea is synthesized only
in liver. Liver releases urea in circulation
from where it extracted by the kidneys, and
is excreted in urine

29. Catabolism of amino acids:
Deamination of amino acid produces
• NH3
• α-keto acid (carbon skeleton)
O
Keto group
NH3

31. 1-The fate of ammonia:
• Ammonia is a toxic compound specially
for nervous system.
NH3(toxic) → Non toxic compound
• Urea biosynthesis occurs in four stages:
1Transamination
2Oxidative deamination
3Ammonia transport from extra hepatic
tissues
4Urea cycle

32. Transamination
• the transfer of an amino (-NH2) group from
a amino acid (Ala) to a-ketoacid (α-KG),
with the formation of a new amino acid
(Glu) &a new keto acid (Pyr). Catalysed
by a group of enzymes called
transaminases (aminotransferases)
Pyridoxalphosphate (PLP)– act as
coenzyme,from the vitamin B6 (pyridoxine),
as a key component in their catalytic
mechanism. .

33. • Liver, Kidney, Heart, Brain contain
adequate amount of these enzymes

36. Main features of transamination
• All amino acids except, lysine, threonine &
proline participate in transamination.
• All transaminases require PLP ( active
form of vit B6).
• No free NH3 liberated, only the transfer of
amino group.
• Transamination is reversible reaction.
• There are multiple transaminase enzymes
which vary in substrate specificity.
• AST & ALT make a significant contribution
for transamination.

37. • Clinical Significance of transaminases
• AST & ALT are enzymes, present within
cell, released in cellular damage into
blood.
↑ AST - Myocardial Infarction (MI).
↑ AST, ALT – Hepatitis, alcoholic cirrhosis.

38. Oxidative deamination
• The removal of amino group from the
amino acid as NH3 is deamination.
• Deamination results in the liberation of
ammonia for urea synthesis.
• Glutamate is only amino acid which
undergoes to oxidative deamination to
liberate free NH3 for urea synthesis

39. • Only liver mitochondria contain glutamate
dehydrogenase (GDH) which deaminates
glutamate to α-ketoglutarate & ammonia.
It needs NAD+ as co-enzyme.
• It is an allosteric enzyme.
• It is activated by ADP & inhibited by GTP.

40. α Keto acid
•TCA intermediates
•Glycolysis intermediates
Acetyl CoA or acetoacetyl CoA
•Energy
•Glucose
•Energy
•Ketone bodies
•Fatty acids
both of (TCA or glycolysis)
intermediates and (acetyl
CoA or acetoacetyl CoA)
2-Fate of carbon skeleton

41. Fate of carbon skeletons:
The carbon skeletons of all amino acids are
undergo
one of the following fates:
1. Glucose ( gluconeogenesis )
2. Ketone bodies ( ketogenesis )

42. • Glucogenic or ketogenic amino acids:
During fasting, those amino acids that are
degraded to pyruvate or 4- or 5-carbon
intermediates of the citric acid cycle (α –
ketoglutarate, oxaloacetate, Succinyl-CoA,
Fumarate) can be used as substrates for
gluconeogenesis.

45. Glucogenic or ketogenic amino
acids
Some amino acids can form:Acetyl CoA
and Pyruvate/CAC intermediates, Their
carbon skeletons can form glucose
as well as fatty acids, These are known as
glyco- and keto-genic amino acids
.

46. • Carbon skeletons of ketogenic amino
acids are :
acetyl-CoA, or acetoacetate.
Acetyl CoA is precursor of acetoacetate,
cannot yield net
• production of oxaloacetate, aprecursor for
gluconeogenesis .

47. Products of Amino Acid
Breakdown
• Glucogenic AA
– Pyruvate– a-Ketoglutarate– Succinyl-CoA
– Fumarate– Oxaloacetate
All of these feed gluconeogenesis
• Ketogenic AA
– Acetyl-CoA – Acetoacetate
All of them feed ketogenesis

49. Fate of Ammonia
• Urea cycle
• Occurs in the liver
Spans two compartments:
mitochondrial matrix and cytosol

50. • The start of the urea cycle may be
considered the synthesis of carbamoyl
phosphate from an ammonium ion and
bicarbonate in liver mitochondria . This
reaction requires two molecules of ATP
and is catalyzed by the enzyme,
carbamoyl phosphate synthetase I (CPS
I), which is found in high concentrations in
the mitochondrial matrix.

51. • The mitochondrial enzyme, CPS I, is
unusual in that it requiresNacetylglutamate
as a cofactor. It is one of two carbamoyl
phosphate synthetase enzymes that have
key roles in metabolism. The second, CPS
II, is found in the cytosol, does not require
N-acetylglutamate, and is involved in
pyrimidine biosynthesis

52. • Ornithine transcarbamoylase catalyzes
the condensation of carbamoyl phosphate
with the amino acid, ornithine, to form
citrulline. In turn, the citrulline is
condensed with aspartate to form
argininosuccinate. This step is catalyzed
by argininosuccinate synthetase and
requires ATP; the reaction cleaves the
ATP to adenosine monophosphate (AMP)
and inorganic pyrophosphate (PPi) (2
ATP equivalents).

53. • The formation of argininosuccinate brings
to the complex the second nitrogen atom
destined for urea
• Argininosuccinate is in turn cleaved by
argininosuccinase, to arginine and
fumarate. The arginine produced in this
series of reactions is then cleaved by
arginase, to a molecule of urea information
and one of ornithine.

54. • The ornithine can then be used to reinitiate
this cyclic pathway, while the diffuses into
the blood, is transported to the kidney, and
excreted in urine.

57. • Biochemical basis of ammonia intoxication
Any defect in urea cycle will lead to
accumulate the ammonia in blood which is
toxic ,and lead to ammonia intoxication.
• Symptoms of ammonia toxicity:
1.Tremors
2.blurring of vision
3.slurring of
• speech
• 4.convulsion
• 5.coma & death.

58. • Causes of ammonia toxicity
1.liver diseases:
Liver hepatitis. Liver tumor,cirrhosis.
2.congenital urea enzyme defect.

60. • Excess ammonia is toxic because:
1.excess ammonia will react with alpha
ketoglutarate of T.C.A cycle lead to stop
T.C. A and decrease energy.
2.ammonia can enter brain and work there
as false neurotransmitter.