The document provides a comprehensive overview of protein metabolism, detailing the key components including the functions, structure, and classification of proteins and amino acids, as well as the digestion and metabolic pathways involved. It discusses the urea cycle, protein energy malnutrition, and the biochemical processes like transamination and detoxification of ammonia. Additionally, it highlights the clinical significance of protein levels in the body and the consequences of metabolic disturbances.

1. PROTEIN METABOLISM
Presented by,
Dr Nikhil V Suresh
First Year PG

2. CONTENT
1. Introduction
2. History
3. Functions of proteins
4. Composition
5. Structure of Amino acids
6. Classification of Amino acids
7. Structure of protein
8. Digestion of protein
9. General Metabolism of protein
10. Urea cycle
11. Metabolic Disturbances of Proteins
12. Inborn errors in metabolism
13. References

3. INTRODUCTION
 Proteins are the most abundant organic molecules of
the living system.
 They occur in every part of the cell and constitute
about 50% of the cellular dry weight.
 Proteins form the fundamental basis of structure and
function of life.
 Amino acids are the monomers that make up proteins

4. HISTORY
 The term protein is derived from a Greek word
“proteios” meaning “holding the first place”
 Berzelius( Swedish chemist) suggested the name
proteins to the group of organic compounds that are
utmost important to life.
 Mulder (Dutch chemist) in 1838 used the term proteins
for the high molecular weight nitrogen- rich and most
abundant substances present in animals and plants

5. FUNCTIONS OF PROTEINS
Static /Structural
•Responsible for structure and strength of
body.
• Collagen and elastin in bone
•Matrix, vascular system and other organs
•a-keratin present in epidermal tissues
Dynamic
•These include proteins acting as enzyme
hormones
•Blood clotting factors
•Immunoglobulins
•Membrane receptors, storage proteins
• Muscle contraction, respiration etc
•Regarded as the working horses of cell

6. COMPOSITION OF PROTEINS
5 major elements:
Carbon-50 - 55%
Hydrogen-6 - 7.3%
Oxygen-19 - 24%
Nitrogen-13 - 19%
Sulphur- 0 – 4%
Estimation of nitrogen in the
laboratory mostly
by Kjeldahl's method is also used
to find out the
amount of protein in biological
fluids and foods

7. AMINO ACIDS
 Amino acids are the monomers that make up
proteins.
 Specifically, a protein is made up of one or more
linear chains of amino acids, each of which is called
a polypeptide.
 There are 20 types of amino acids commonly found
in proteins.

8. STANDARD AMINO ACIDS
Amino acids are a group of
organic compounds containing
two functional groups amino
and carboxyl.
• amino group (-NH2) is basic
while
•carboxyl group (-COOH) is
acidic in nature

9. • Each amino acid has 4 different groups attatched to α-
carbon ( which is Catom next to COOH).
• These 4 groups are :amino group, COOH group ,
Hydrogen atom and side chain(R).

10. CLASSIFICATION OF AMINO ACIDS
A. Amino acid classification based on the Structure
B. Classification of amino acids based on Polarity
C. Nutritional classification of amino acids

11. AMINO ACID CLASSIFICATION BASED ON
THE STRUCTURE
1. Amino acids with aliphatic side
chains
• These are mono-amino mono-
carboxylic acids.
• Glycine
• Alanine
• Valine
• Leucine
• Isoleucine.
2. Hydroxyl group containing amino
acids :
•Serine
•Threonine
•Tyrosine
•(Tyrosine-being aromatic in nature-is
usually considered under aromatic
amino acids)

12. 3. Sulfur containing amino acids :
• Cysteine - sulfhydryl group
• Methionine -thioether group
4. Acidic amino acids and their amides
•Aspartic acid
• Glutamic acids
•Asparagine
• Glutamine
dicarboxylic mono
amino acids
are their
respective
amide
derivatives.

13. 5. Basic amino acids :
The three amino acids:
• Lysine
•Arginine (with guanidino group)
• Histidine (with imidazole ring)
are dibasic monocarboxylic acids.
6. Aromatic amino acids :
•Phenylalanine
•Tyrosine
•Tryptophan (with indole ring are
aromatic amino acids)
• Besides these, Histidine may also be
considered under this category.
7. lmino acids:
•Proline containing pyrrolidine ring is a unique amino acid.
•lt has an imino group (=NH), instead of an amino group (-
NH2) found in other amino acids.

14. CLASSIFICATION OF AMINO ACIDS
BASED ON POLARITY
1. Non-polar amino acids- They have no charge on the 'R' group. Eg- Alanine,
Leucine, Isoleucine, Valine, Methionine, Phenylalanine,Tryptophan and Proline
2. Polar amino acids with no charge on 'R‘ Group- hydroxyl, sulfhydryl and
amide and participate in hydrogen bonding of protein structure . Eg- Glycine,
Serine, Threonine, Cysteine,Glutamine, Asparagine and Tyrosine.
3. Polar amino acids with positive 'R' group- Lysine, Arginine and Histidine
4. Polar amino acids with negative 'R'group- The dicarboxylic monoamino acids
–Aspartic acid and Glutamic acid

17. STRUCTURE OF PROTEIN
 Proteins are polymers of L-A-amino
acids
 Structure of protein is complex which
can be divided into 4 levels of
orgnisations:
1. Primary structure
2. Secondary structure
3. Tertiary structure
4. Quaternary structure

18. PRIMARY
STRUCTURE
- determined by
covalent bonds
Secondary,Tertiary,
Quaternarystructure - determined by
weak forces

19.  The primary structure of protein refers to the
sequence of amino acids present inthe
polypeptide chain.
 Amino acids are covalently linked by
peptide bonds or covalentbonds.
 Eachcomponent amino acid in a
polypeptide is called a"residue”or
“moiety”.
 Byconvention the primary structure of protein
starts from the amino terminal(N) end and
ends in the carboxyl terminal (C) end.
PRIMARY STRUCTURE

20. It is a local, regularly
occurring structure in proteins
and is mainly formed through
hydrogen bonds between
backbone atoms.
Pauling &Corey studied the
secondary structures and
proposed 2 conformations
o α helix
o β sheets.

21.  Right handed spiral structure.
 Side chain extend outwards.
 Stabilized by H bonding that are
arranged such that the peptide
Carbonyl oxygen (nth residue) and
amide hydrogen(n+4 th residue).
 Amino acids per turn – 3.6
 Pitch is 5.4 A°
 Alpha helical segments, are found
in many globular proteins like
myoglobin,troponin C.

22. o Formed when 2 ormore
polypeptides line up sideby
side.
o Individual polypeptide –
beta strand.
o Each beta strand is fully
extended.
o They are stabilized by
hydrogen bond between N-
H and carbonyl groups of
adjacent chains.

23.  The tertiary structure defines the specific overall 3-D shape
of the protein.
 Tertiary structure is based on various types of interactions
between the side-chains of the peptide chain

24.  The quaternary protein structure involves the
clustering of several individual peptide or protein
chains into a final specificshape.
 Avariety of bonding interactions including hydrogen
bonding, salt bridges, and disulfide bonds hold the
various chains into a particulargeometry.
 Two kinds of quaternary structures: both aremulti-
subunit proteins.
Homodimer :association between identical
polypeptide chains.
Heterodimer :interactions between subunits of
very different structures.

25. Primary
Secondary
Tertiary
Quaternary
Folding
Packing
Interaction
Linear
arrangement

26. DIGESTION OF PROTEINS
• The dietary proteins are denatured on cooking and
therefore more easily to digested by a digestive enzymes.
• All these enzymes are hydrolases in nature.
• Proteolytic enzymes are secreted as inactive zymogens
which are converted to their active form in the intestinal
lumen.
• This would prevent autodigestion of the secretory
acini.

27. THE PROTEOLYTIC ENZYMES INCLUDE:
• Endopeptidases:
They act on peptide bonds inside the protein molecule, so that the
protein becomes successively smaller andsmaller units. This
group includes pepsin, trypsin, chymotrypsin, and elastase.
• Exopeptidases:
This group acts at the peptide bond only at the end regionof the
chain.
• This includes carboxypeptidase acting on the peptide only at the
carboxyl terminal end on the chain
• A
minopeptidase, which acts on the peptide bond only at the
amino terminal end of the chain.

28. A. GASTRIC DIGESTION OF PROTEINS:
• In the stomach, hydrochloric acid is
secreted. It makes the pH optimum for the
action of pepsin and also activates pepsin.
•The acid also denatures the proteins. But
hydrochloric acid at body temperature could
not break the peptide bonds.
•Thus in the stomach, HCl alone will not
able to digest proteins; it needs enzymes.

29. 1) RENNIN:
• Rennin otherwise called chymosin, is active in infants and is
involved in the curdling of milk. It is absent in adults.
• Milk protein, casein is converted to paracasein by
the action ofrennin.
• The denatured protein is easilydigested further by pepsin.

30. 2) PEPSIN:
• It is secreted by the chief cells of stomach as
inactive pepsinogen.
• The conversion of pepsinogen to pepsin is
brought about by the hydrochloric acid.
• The optimum pH for activity of pepsin is around
2.

31. B. PANCREATIC DIGESTION OF PROTEINS:
• The optimum pH for the activity of pancreatic
enzyme (pH 8) is provided by the alkaline bile and
pancreatic juice.
• The secretion of pancreatic juice is stimulated by the
peptide hormones, cholecystokinin and pancreozymin.
• Pancreatic juice contains the important
endopeptidases, namely trypsin, chymotrypsin,
elastase and carboxypeptidase

32. 1) TRYPSIN:
• Trypsinogen is activated by enterokinase present on the intestinal
microvillus membranes. Once activated, the trypsin activates
other enzyme molecules.
•Trypsin catalyzes hydrolysis of the bonds formed by carboxyl
groups of Arg and Lys.
•Acute pancreatitis: Premature activation of
trypsinogen inside the pancreas itself will result in the
autodigestion of pancreatic cells. The result is acute
pancreatitis. It is a life-threatening condition

33. 2) CHYMOTRYPSIN:
• Trypsin will act on chymotrypsinogen, so that the active
site is formed. Thus, selective proteolysis produces the
catalytic site.
3) Carboxypeptidases:
• Trypsin and chymotrypsin degrade the proteins into small
peptides; these are further hydrolyzed into dipeptides
and tripeptides by carboxypeptidases present in the
pancreatic juice. They are metallo-enzymes requiring
zinc.

34. C. INTESTINAL DIGESTION OF PROTEINS:
 Complete digestion of the small peptides to the
level of amino acids is brought about by enzymes
present in intestinal juice (succus entericus).
•The luminal surface of intestinal epithelial cells
contains Amino- peptidases, which release the N-
terminal amino acids successively.

35. GENERAL METABOLISM OF AMINOACIDS:
• Anabolic pathway
• Catabolic pathway
13

36. General metabolism of amino acids:
• Dietary proteins and body proteins are broken down to amino
acids. This is called catabolic reactions.
• In transamination reaction, amino group of amino acid is removed
to produce the carbon skeleton (keto acid). The amino group is
excreted as urea.
• The carbon skeleton is used for synthesis of non- essential amino
acids.
• It is also used for gluconeogenesis or for complete oxidation.
• Amino acids are used for synthesis of body proteins; this is anabolic
reaction.

37. FORMATION OF AMMONIA
• The first step in the catabolism of amino
acids is to remove the amino group as
ammonia.
• Ammonia is highly toxic especially to the
nervous system.
• Detoxification of ammonia is by conversion to
urea and excretion through urine.

38. A. TRANSAMINATION
• Transamination is the exchange of amino group
between amino acid and another keto acid,
forming a new alpha amino acid.
• The enzyme catalyzing the reaction as a group
known as transaminases (amino transferases).
• These enzymes have pyridoxal phosphate as
prosthetic group.
• The reaction is readily reversible.

39. 17

40. BIOLOGICAL SIGNIFICANCE OF TRANSAMINATION
1. First step of catabolism:
 Ammonia is removed, and rest of the amino acid
is entering into catabolic pathway.
2. Synthesis of non-essential amino acids:
 By means of transamination, all non-essential
amino acids could be synthesized by the body from
keto acids available for other sources 18

41. B. TRANS-DEAMINATION
• It means transamination followed by oxidative deamination.
• All amino acids are first transaminated to
glutamate, which is then finally deaminated.
• Glutamate dehydrogenase reaction is the final reaction which
removes the amino group of all amino acids.
20
AA+ketoacid1 Ketoacid2+ Glutamate Amino
grp+ketoacid3
transamination Trans-deamination

45. 21

47. DISPOSAL/DETOXIFICATION OF AMMONIA
1. First line of defense (Trapping of ammonia):
• Even very minute quantity of ammonia may produce
toxicity in central nervous system.
• The intracellular ammonia is immediately trapped by glutamic acid
to form glutamine, especially in brain cells.
• The glutamine is then transported to liver,where the reaction is
reversed by the enzyme glutaminase.
• The ammonia thus generated is immediately detoxified into urea.
22

48. 2. FINAL DISPOSAL:
• The ammonia from all over the body thus
reaches liver.
•It is then detoxified to urea by liver cells.
• Then excreted through kidneys.
• Urea is the end product of protein
metabolism
23

49. UREA CYCLE

50. UREA CYCLE
• The cycle is known as Krebs-Henseleit urea
cycle.
• As ornithine is the first member of the reaction
sequences, it is called as Ornithine cycle.
• The two nitrogen atoms of urea are derived from
two different sources, one from ammonia and
the other directly from aspartic acid.
24

51. STEPS OF UREA CYCLE
1. Formation of Carbamoyl Phosphate.
2. Formation of Citrulline.
3. Formation of Argininosuccinate.
4. Formation of Arginine.
5. Formation of Urea.
26

52. STEPS OF UREA CYCLE

53. 28

54. REGULATION OF THE UREA CYCLE
• During starvation, the activity of urea cycle
enzymes is elevated to meet the increased
rate of protein catabolism.
• The major regulatory steps is catalyzed by
CPS-I (Carbamoyl phosphate synthetase-I)
where the positive effectror is N-acetyl
glutamate (NAG).
29

55. DISORDERERS OF UREA CYCLE
• Deficiency of any of the urea cycle enzymes
would result in hyperammonemia.
• If block occur in one of the earlier steps, the
condition is more severe, since ammonia itself
accumulates.
• If deficiency occur in later enzymes, this result
in accumulation of other intermediates which
are less toxic and hence symptoms are less. 30

56. • The accumulation of ammonia in
blood (normally less than 50
mg/dl) and body fluids results in
toxic symptoms.
• Brain is very sensitive to ammonia.
• Child may be put on a low protein diet
and frequent small feeds are given.
• Since Citrulline is present in
significant quantities in milk,
breast milk is to be avoided in
Citrullinemia.
31

57. UREA LEVEL IN BLOOD AND URINE
• In clinical practice, blood urea level is taken as an indicator of
renal function.
• The normal urea level in plasma is from 20 to 40 mg/dl.
• Blood urea level is increased where renal function is inadequate.
• Urinary excretion of urea is 15 to 30 g/day (6-15 g
nitrogen/day).
• Urea constitutes 80% of urinary organic solids.
32

58. METABOLIC DISTURBANCES OF PROTEINS
I. Protein Energy Malnutrition (PEM) :-
•PEM is a spectrum of diseases whose
essential feature is a deficiency of protein
at one end as in Kwashiorkor and ;
•total inanition(starvation of infant due to
severe and prolonged restriction of all food
at other end as in Marasmus.
•In the middle of spectrum,there is
Marasmic Kwashiorkor in which there are
clinical features of both disorders.

59.  Causes of PEM :-
 Dietary deficiency
 Serious illness
 Infections in babies
 Low socio-economic status
 Problems in mother leading to inadequate
production of milk
 Dietary factors like inadequate breast feeding, ignorance
of weaning

60. PEM IS PRESENTED AS :-
 Kwashiorkor
 Marasmus

61. KWASHIORKOR
 Its a maladaptive response to starvation due to lack
of physiological adaptation to unbalanced deficiency
where body utilizes proteins and conserves fat
 Occurrence –
Seen predominantly between 1-5 years of age
 Causes –
Due to insufficient intake of proteins, as the diet of
weaning child mainly consists of carbohydrates

62.  Clinical symptoms -
 Weight is about 60-80 % of normal as loss of true weight is
maskedby increased fluid retention
 Generalized edema
 Swollen abdomen
 Moon face
 Characteristic skin lesions with alternating layers of
hyperpigmentation, desquamation hypopigmentation; giving
a flaky paint appearance
 Hair changes like loss of colour or alternate bands of pale
and darker colour, straightening and loss of firm
attachment to scalp
 Eyelashes give a ‘Broomstick’ appearance
 Dehydration (due to diarrhoea and vomitting)
 Prone to infections
 Psychomotor changes (due to cerebral atrophy)

64.  Oral manifestations of Kwashiorkor
 Mouths of Kwashiorkor patients have been described by Van Wyk to be dry, dirty,
caries free, easily traumatized with epithelium readily become detached from the
underlying tissue, leaving a raw, beeding surface
 Bilateral angular cheilosis (inflammation)
 Fissuring of lips
 Loss of circumoral pigmentation
 Crowded and rotated teeth giving an appearance of mouth full of
jumbled teeth
 Delayed eruption and hypoplasia of deciduous teeth
 Incisor and molar growth is retarded
 Radicular osteocementum decreased
 Increased acid solubility of enamel of incisors
 Decreased salivary volume

65. MARASMUS
d
 Its an adaptive response to starvation
 Occurrence –
Seen mostly in the first year of life
 Causes –
Due to deficiency of calories

66.  Clinical symptoms –
 Growth retardation due to low calorie intake
 Loss of muscle mass as muscle proteins are
mobilised as use for fuel to provide body with a.a
as a source of energy to compensate malnutrition.
 Due to muscle wasting rib cage is prominent
 Subcutaneous fat is lost due to lipolysis
 Lean body, so head appears too large
 Body weight falls to 60 % of normal
 Child looks older than his age
 Sparse hair and wrinkled appearance (Old man
face)
 Bones are prominent due to absence of fat around
them

68. DIFFERENTIATION BETWEEN KWASHIORKOR AND
MARASMUS
KWASHIORKOR
1. Malnutrition that occurs due to
insufficient intake of proteins
2. Large belly, diarrhoea, pigmented skin,
hair changes
3. Children of 1-5 yrs age
4. Weaned from mother’s milk to a diet
low in protein
5. Edema-Present (pitting type)
6. 60-80 % of normal body wt.
7. Decreased plasma albumin
8. Treated by High protein foods
MARASMUS
1. Malnutrition that occurs due to
starvation (i.e deficiency of proteins,
carbs. and fats in diet
2. Muscle wasting, skin foldings,
prominent rib cage , shrunken
abdomen
3. Children under 1 yr
4. Failed breastfeeding (inadequate
calorie intake)
5. Absent, rather wasting
6. Less than 60 % of normal
7. Normal / slightly decreased plasma
albumin
8. Treated by a Well banced diet

69. KWASHIORKOR MARASMUS

70. AMYLOIDOSIS
Disorder characterized by extracellular deposits
of fibrillar proteins which is a result of
aggregation of misfolded proteins.
Misfolded proteins being unstable start self
associating forming oligomers and fibrils that
are deposited in tissues.

71.  Clinical manifestations :-
 Weakness,fatigue,weightloss
 Renal and hepatic diseases
 Proteinuria
 Cardiac arrythemia
 Changes in skin color
 Clay-colored stools
 Feeling of fullness
 Joint pain
 Low red blood cell count (anemia)
 Shortness of breath
 Swelling of the tongue
 Tingling and numbness in legs and feet
 Weak hand grip

72.  Oral manifestations :-
A. Tongue amyloidosis
B. Palatal amyloidosis

73. A. TONGUE AMYLOIDOSIS :-
 Feature of systemic amyloidosis
 Macroglossia with nodular deposits
 Lateral ridging of enlarged tongue due to teeth
indentation
 Firm tongue with yellow nodules on lateral surface
 Interference with taste and hyposalivation may result from
amyloid deposition in salivary glands
 Xerostomia and tongue pain
 Sub mandibular swelling due to tongue enlargement can lead to
respiaratory obstruction.

74. B. PALATAL AMYLOIDOSIS :-
 Rare condition
 Feature of localized amyloidosis
 Nodular deposits found on palate ,nasal septum
and maxillary sinus.

75.  INBORN ERRORS OF AMINO ACID
METABOLISM
 DISORDERS OF PHENYLALANINE AND TYROSINE
 PHENYLKETONURIA
 ALKAPTONURIA
 ALBINISM
 HARTNUP DISEASE

76. INBORN ERRORS OF AMINO ACID METABOLISM:-
 Phenylketonuria :-
Enzyme defect in Phenylalanine / tyrosine
degradation leading to metabolic disorder. Here, the
deficiency of hepatic enzyme Phenylalanine
Hydroxylase results in accumulation of
Phenylalanine.
 Phenylalanine
P
.HYDROXYLASE
Tyrosine

77.  Oral manifestations –
 Prominent cheek and jaw bones
 Widely spaced teeth
 Poor development of tooth enamel.
 Patients are susceptible to tooth wear(erosion)

78. Alkaptonuria :-
Its due to absence of Homogentisate oxidase
activity which is necessary for breakdown of
Homogenetisic acid. As such Homogentisate
accumulates in tissues .
Phenylalanine Tyrosine Homogenitisic acid
H.OXIDASE
Intermediates in TCA

79.  Clinical features –
 Dark urine : also known as Black Urine disease
urination
Homogenetistic acid Alkapton (Black colur)
 Ochronosis (alkapton deposition in bones, nose,
ear,eyes, etc.)
 Arthritis

80. Albinism :-
It is due to lack of synthesis of pigment Melanin
which is due to defect in tyrosinase enzyme, the
most responsible enzyme for Melanin synthesis.
PHENYLALNINE TYROSINE
Tyrosinase
DOPA

81.  Clinical features –
 Photophobia
 Susceptibility to Parkinson’s disease (as no DOPA formed)
 Hypopigmentation in the form of :
i. Vitiligo – loss of pigmentation around mouth, nose,
eyes, nipples
ii. Leukoderma – loss of pigmentation begins with hands

82. REFERENCES
 U.satyanarayan textbook of biochemistry (3rd
edition)
 Shafer’s Textbook of oral pathology (7th
 Robbin’s book of basic pathology (9th
edition)
 Davidson’s book of medicine (22nd edition)
 Neville’s textbook of oral and maxillofacial
pathology (2nd edition)

83. THANK YOU