DISORDERS OF PROTEIN METABOLISM

1. DISORDERS
OF
PROTEIN
METABOLISM
PRESENTED BY
BAZILA
ILLAHI
BDS 3RD YEAR
ROLL NO : 15

2. CONTENTS :
 BRIEF OVERVIEW OF PROTEINS
 DEFINITION OF PROTEINS
 TYPES OF PROTEINS
 BIOLOGICAL FUNCTIONS
 ROLE IN DENTISTRY
 PROTEIN METABOLISM OVERVIEW
 METABOLIC DISTURBANCES OF
PROTEINS

3. PROTEIN ENERGY MALNUTRITION
AMYLOIDOSIS
GOUT
PRION DISEASE
INBORN ERRORS OF METABOLISM

4. DEFINITION OF PROTEINS

5. STRUCTURE OF A PROTEIN

6. SOURCES OF PROTEINS
 Meat
 Fish
 Cheese
 Beans
 Yogurt
 Nuts
 Lentils
 Seeds
 Eggs

7. DAILY REQUIREMENTS
One gram of protein is required for each kg of body
weight.
However requirement can increase in various normal
physiological situations like:
 Last half of pregnancy
 During lactation
 Infancy
 Childhood
 Adolescence

8. TYPES OF PROTEINS
On the basis of composition :
1. Simple proteins :- contain only a.a
2. Conjugate proteins :- contain a non a.a component in addition to
the a.a
3. Complete proteins :- contain sufficient amount of essential a.a
4. Incomplete proteins :- contain insufficient quantities of one or
more essential a.a
5. Complementary proteins :- incomplete when ingested singly,but
when combined provide sufficient essential a.a

9. TYPES OF PROTEINS (CONTD.)
On the basis of function :
1. Hormonal
2. Enzymatic
3. Structural
4. Defensive
5. Storage
6. Transport
7. Receptor
8. Contractile

10. BIOLOGICAL FUNCTIONS
 Static functions :- provides stucture and strength to the body e.g
collagen.
 Dynamic functions :- hormonal, enymatic, defensive etc.
 Source of energy
 Role in dentistry :-
 Pre-eruptive and post-eruptive effects on teeth as they form an
integral component of cells necessary for the normal development
of teeth and specifically for the formation of matrix of hard tissues
of teeth e.g Amelogenin,BMP.
 Chemical nature of protein foods can neutralize the acids produced
by oral bacteria.
 Dental pellicle- an acellular layer of salivary proteins protects the
enamel against abrasion and serves as a diffusion barrier thus
preventing the solubility of enamel surface.

11. PROTEIN METABOLISM OVERVIEW
Dietary protein body proteins
Protein synthesis amino acids synthesis of N-compounds
α-ketoglutarate
transamination
glutamate
deamination
ketoacids ammonia
urea
Energy Glucose Fat Non-essential amino acids

12. PROTEIN METABOLISM (CONTD.)
Amino acid contains two components:
 Carbon skeleton- its converted to keto acids
a.a transamination Keto acids
.
 Amino group- its converted to urea as an excretory product.
a.a deamination Urea

13. 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.

14.  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

15.  PROTEIN ENERGY MALNUTRITION
a) KWASHIORKOR
b) MARASMUS
 CAUSES
 CLINICAL MANIFESTATIONS
 INVESTIGATIONS
 TREATMENT

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

17. KWASHIORKOR
 Introduction –
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

18.  Biological manifestations –
 Decreased plasma albumin levels
 Visceral compartment is severely affected
 Hypoproteinemia and hypoglycemia
 Decreased level of electrolytes
 Low enzyme levels
 Percentage of body water is increased
 Iron deficiency anemia
 Fatty liver (due to decreased synthesis of carrier proteins of
lipoproteins)
 Hypoplastic bone marrow
 Decreased immunity
 Multi-vitamin deficiency

19.  Clinical symptoms -
 Weight is about 60-80 % of normal as loss of true weight is masked by
increased fluid retention
 Generalized edema (due to decreased colloidal osmotic pressure) of
pitting variety
 Sparing of subcutaneous fat and muscle mass as body utilizes its
proteins to compensate the deficient state
 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
 Diarrhoea (due to impaired synthesis of digestive enzymes and loss of
electrolytes in stools)
 Eyelashes give a ‘Broomstick’ appearance
 Dehydration (due to diarrhoea and vomitting)
 Prone to infections
 Psychomotor changes (due to cerebral atrophy)

21.  Oral manifestations of Kwashiorkor –
 Bright reddening of tongue with loss of papillae
 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
 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
 Incisor and molar growth is retarded
 Radicular osteocementum decreased
 Increased acid solubility of enamel of incisors
 Decreased salivary volume

22.  Oral cytological smear study –
Perinuclear vacuolization or halo around nucleus in a
remarkable number of epithelial cells which is interpreted as
a sign of atrophy
 Investigations –
A. Routine tests :-
• Full blood count -
• Stool and urine study – KETONURIA
• Blood glucose profile - HYPOGLYCEMIA
• Hb estimation - ANEMIA
B. Non-routine tests :-
• Hair analysis – ALTERNATE BANDS OF HAIR
• Skin biopsy - PARAKERATOSIS WITH DESQUAMATION
• Oral findings – BLEEDING SURFACE

23.  Treatment –
 Provide adequate nutrition by dietary supplements
 Restore normal body composition
 Dietary support in the form of 3-4 gm protein and 200
cal/kg body weight
 Cure the conditions that cause the deficiency
 Prevention –
 Breastfeeding a baby for at least 6 months to prevent
PEM
 Improved food distribution systems, public health
programs and agricultural development should be
promoted

24. MARASMUS
 Introduction –
Its an adaptive response to starvation
 Occurrence –
Seen mostly in the first year of life
 Causes –
Due to deficiency of calories
 Biological manifestations –
 Serum albumin level normal or slightly decreased
 Somatic compartment of proteins is lost
 Anemia
 Multi vitamin deficiency
 Immune deficiency
 Hypoplastic bone marrow with increased red cell precursors

25.  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
 Weakened body is under stress
 More chances of infections
 Dry and baggy skin
 Sparse hair and wrinkled appearance (Old man face)
 No edema
 Bones are prominent due to absence of fat around them
 Hypotension and slow pulse

27.  Investigations –
 Full blood count -
 Electrolyte, serum protein level study –
ALBUMIN LEVEL NORMAL OR LOW.
 Blood glucose level -
 Treatment –
 Dietary support by giving food as proteins and supplements
 Bring the child out of starvation

28. POINTS OF DIFFERENTIATION BETWEEN
KWASHIORKOR AND MARASMUS
KWASHIORKOR MARASMUS
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
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

29. KWASHIORKOR MARASMUS

30.  AMYLOIDOSIS
 INTRODUCTION
 PATHOGENESIS
 CLASSIFICATION
 CLINICAL MANIFESTATIONS
 ORAL MANIFESTATIONS
 DIAGNOSIS
 BIOPSY EXAMINATION
 VARIOUS TESTS
TREATMENT

31. AMYLOIDOSIS
 Introduction :-
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 r
deposited in tissues.

32.  Pathogenesis :-

33. FORMS OF AMYLOID PROTEINS :-
1. Amyloid light chain protein (AL)- Here IG light
chains accumulate due to monoclonal B cell
proliferation affecting heart
2. Amyloid associated protein ( AA)- Here SAA
accumulates due to increased activation by chronic
inflammatory mediators affecting liver mainly.
3. AB amyloid – Here APP deposits in the cerebral
vessels.
4. Transthyretin – Here ATTR accumulates due to
mutation of normal transthyretin.
5. B2 Microglobulin – accumulates in patients with
renal disease ,with deposits in joints.

34.  Classification :-
 Systemic amyloidosis –
 Immunocyte dyscrasias wth Amy. (AL Protein accumulation)
 Reactive sytsemic Amy. (AA Protein)
 Heriditary amyloidosis –
 Familial mediterranean fever (AA Protein)
 Senile Amy. (ATTR Protein)
 Familial amyloidotic neuropathies (ATTR Protein)
 Localized amyloidosis –
 Senile cerebral (AB Protein)
 Senile cardiac (ATTR Protein)

35.  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

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

37. 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 n tongue pain
 Sub mandibular swelling due to tongue enlargement can
lead to respiaratory obstruction.

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

39.  Diagnosis :-
It requires
 Demonstration of amyloid in tissues
 Demonstration of plasma cell dyscrasia
o For demonstration of tissue amyloid :-
1. BIOPSY - Fine needle aspiration of abdomenal fat.
Tissues for non-invasive biopsy are gingiva, salivary
glands, rectum and skin.
 Histological feature is Apple Green Birefringence
with Congo red dye and viewed under polarised
microscope. Other dyes like Thioflavin,Hematoxylin
and Eosin are also used.

40. APPLE GREEN BIREFRINGENCE SEEN IN
HISTOLOGIC SECTION

41. o For demonstration of plasma cell dyscrasia :-
1. Bone marrow biopsy showing gamma and kappa
light chain producing plasma cells.
2. Presence of monoclonal light chains in serum and
urine.
3. Serum Free Light Chain assay (FLC)
o Imaging techniques for assessment of organ
involvement

42.  Treatment :-
(Aim is to reduce the supply of amyloidogenic monoclonal light chains by
suppressing the underlying Plasma cell dyscrasia)
 High-dose chemotherapy withstem cell transplant
can help remove the substance that leads to
amyloid formation in those with primary AL
amyloidosis.
 Secondary (AA) amyloidosis is treated with
powerful anti-inflammatory medicines called
steroids, which fight inflammation.
 Liver transplant may stop the disease in those with
hereditary amyloidosis.

43.  A kidney or heart transplant may also be
recommended.
 Diuretic medicine to remove excess water from
your body
 Thickeners to add to fluids to prevent choking in
those who have swelling of the tongue
 Compression stockings to relieve swelling in the
legs or feet
 Diet modifications, especially for those with
gastrointestinal amyloidosis

44.  GOUT
 INTRODUCTION
 PATHOGENESIS
 CLINICAL MANIFESTATIONS
 ORAL MANIFESTATIONS
 DIAGNOSIS
 TREATMENT

45. GOUT
 Introduction –
Gout is an inflammatory disease caused by deposition
of monosodium urate monohydrate crystals in and
around synovial joints.
 Epidemology –
Levels are higher are in men, increase with age and are
associated with body weight
.
 Pathophysiology –
It can be due to diminished renal excretion ; or
increased intake of red meat ; or
over production of uric acid .

47.  Clinical features –
 Severe pain
 Extreme tenderness
 Marked swelling with overlying red
shiny skin
 Crystals may deposit in joints and soft tissues to produce irregular
firm nodules called TOPHI.
 Investigations –
 Aspiration of urate crystals from a joint, bursa and tophus
 Biochemical screen including renal function, uric acid, glucose
and lipid profile should be performed
 Levels of ESR and CRP
 Radiographs

48.  Treatment –
 Oral NSAIDs for pain relief
 Local icepacks
 Oral colchicine
 Joint aspiration with intra articular steroid injection
 Oral corticosteroids
 Urate lowering therapy
 Allopurinol drug which reduces conversion of
hypoxanthine and xanthine to uric acid.

49. PRIONS
 Are the unique proteineceous infectious agents.
 Devoid of nucleic acid.
 Transmitted by acquisition of normal mammalian protein
(prion protein PrPc) which is in an abnormal
conformation(PrPsc ) due to replacement of alpha helices
by beta sheets.
 The abnormal protein inhibits the enzyme proteasome
26S, leading to vicious circle of further accumulation of
abnormally configured PrPsc instead of normally
configured PrPc.

51. PRIONS DISEASES
 Introduction –
Rare disorders which include diff. forms of
CREUTZFELDT JAKOB Disease (CJD) as well as
animal diseases such as SCRAPIE disease in sheep
and Mad cow disease in cattles.
 Epidemology –
Common in middle aged to elderly.
 Pathology –
Due to mutations in gene coding for prion protein.

52. PATHOPHYSIOLOGY OF PRION DISEASE

53. Oral manifestations of prions diseases are
extremely rare with features as :-
 Pseudobulbar palsy may cause dysphagia.
 Dysarthria and Orofacial dysesthesia .
 Paresthesia, as well as loss of taste and smell.

54.  Clinical features –
 Progressive dementia
 Characteristic EEG pattern due to brain atrophy
 Visual disturbances
 Diagnosis –
 By immunohistochemical staining
 Blood test
 EEG
 Cerebrospinal fluid test

55. PREVENTION –
The theoretical risk of
transmission of prion
disease through dental
treatment points to the
importance
of maintaining optimal
standards of infection control
and
decontamination for infectious
agents, including prions.

56.  INBORN ERRORS OF AMINO ACID
METABOLISM
 DISORDERS OF PHENYLALANINE N
TYROSINE
 PHENYLKETONURIA
 TYROSINEMIA
 ALKAPTONURIA
 ALBINISM
 CYSTINURIA
 CYSTINOSIS
 HARTNUP DISEASE
 MAPLE SYRUP DISEASE

57. INBORN ERRORS OF METABOLISM

58. 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 Tyrosine
P.HYDROXYLASE
Phenyketonuria

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

60.  Clinical manifestations –
 Mental retardation due to its accumulation
 Hypopigmentation of hair and skin
 Treatment –
 Diet low in phenylalanine amino acid
 Diet with sufficient amount of tyrosine (to
compensate for its absence)

61. 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
Alkaptonuria Intermediates in TCA

62.  Clinical features –
 Dark urine : also known as Black Urine disease
Homogenetistic acid urination Alkapton (Black colur)
 Ochronosis (alkapton deposition in bones, nose,
ear,eyes, etc.)
 Arthritis
 Treatment –
Not a dangerous disorder,
so no specific treatment.

63. 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
ALBINISM

65.  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

66. Tryosinemia :-
It results due to loss of Tyrosine
transaminase which is required for the
degradation of Tyrosine. (Type 1)
Phenylalanine Tyrosine
T.transaminase
TYROSINEMIA Breakdown product

67.  Clinical features –
 Hepatic dysfunction, cirrhosis
 Liver failure
 Hyperkeratosis
 Treatment –
 Diets low in in Tyrosine,
Phenylalanine are
recommended.

68. Cystinuria :-
Characterized by increased excretion of Cystine
due to defective carrier system which is normally
present for re-absorption of amino acids leading to
excretion of amino acids in urine .
Cystine Reabsorption
carrier system in kidney
Cystinuria

69.  Clinical features –
 Cystine stones in kidneys (due to its insolubility)
 Treatment –
 Aim of treatment
is to increase its solubility
and thus reduce stone
formation in kidneys.

70. Homocystinuria :-
Due to accumulation of homocystine
 Features –
 Thrombosis,
 Osteoporosis,
 MI, Stroke, etc

71. Hartnup’s disease :-
It’s a hereditary disorder of Tryptophan metabolism
characterized by low plasma levels of Tryptophan and
their elevated urinary excretion.
 Clinical manifestations –
 Rash, light sensitivity
 Cerebellar ataxia
 Dermatitis
 Mental retardation
 Treatment –
 Dietary Niacin is given

72. Maple Syrup Urine Disease :-
It’s a metabolic disorder of branched chain amno
acids. The urine smells like Maple syrup or Burnt
sugar, hence the name .
Branched chain keto a.a Acetyl CO-
A
acid dehyrogenase
MSUD

73.  Symptoms –
 Lethargy
 Maple syrup odour of urine
 Coma
 Mental retardation
 Treatment –
 To feed with a diet having low content of branched
chain amino acids

74. Isovaleric acidemia :-
Inborn error of leucine metabolism with defect in
enzyme Isovaleric Co-A dehyrogenase.
 Oral manifestation –
Cheesy odour in breath
 Treatment –
Limit intake of leucine in diet

75. Cystinosis :-
Cystine storage disease where cystine crystals are
deposited in many tissues n organs of RES .
 Cause –
Lysosomal dysfunction

76. Glycinuria :-
When excessive amount of glycine is excreted in
urine due to defective renal reabsorption .
 Symptoms –
Increased tendency for formation of oxalate crystal
stones.

77. BIBLIOGRAPHY
 Shafer’s Textbook of oral pathology (7th edition)
 U.satyanarayan textbook of biochemistry (3rd edition)
 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)
 Neurol Neurosurg Psychiatry 2004;75(Suppl I):i36–i42. doi:
10.1136/jnnp.2004.036137
 PEM by Keith P. West, Jr., Dr.P.H.international nutrition
 Oral Manifestations of Malnutrition III. The Effect of
Proteins
Pages with reference to book,
From 119 To 122 Mohammad Iqbal Khadim ( Dentistry
Department, Khyber Medic College, Peshawar. )