2. Fondos privados 38
2.8 Principios de Ecuador para el sector financiero
6. Hb-Constant Spring
It produces an unstable m-RNA. In this the UAA stop- codon has mutated to a CAA which codes for Glutamine. Hence α-chains are 31 residues longer than normal (i.e., in place of 141 amino acids, it has 172 amino acids). The longer m-RNA is unstable and gets degraded readily.
Other abnormal haemoglobins: Some of the other abnormal haemoglobins are Hb-C, Hb-D (Panjab), Hb-E, etc. Substitution of amino acid and molecular formulae are given below in the box.
Hb-C is confined amongst Negroes in West Africa. All of them bring about change in red cell morphology, affect solubility and may produce mild haemolytic anaemia. Hb- C and Hb-D can occur with Hb-S.
THALASSAEMIAS
Impairment of synthesis of a single kind of Hb-chain result in thalassaemias, so called because the conditions are more common in Mediterranean countries (“thalasa” = derived from Greek word meaning “sea”). The α-chain thalassaemia is also prevalent in SE Asia, with an occurrence of 1 in 100 in Thailand. They occur due to mutation of Regulator gene.
1. ααααα-chain Thalassaemias
Synthesis of α-chains are repressed and there occurs a compensatory increase in synthesis of other chains of which the cell is capable either β-chains or γ-chains. (a) Hb-H (βββββ4): In this there is inhibition of ααααα-chain synthesis
and rate of βββββ-chain production increases. The excess of Other abnormal Hbs
Type Chain affected Change in amino acid sequence Formula
• Hb-C β-chain Glutamic acid at 6 replaced by lysine α2 β2
• Hb-D (Panjab) β-chain Glutamic acid at position 121 is replaced α2 β2
by Glutamine
• Hb-E β-chain Glutamic acid at 26 is replaced by lysine α2A β2
A A 6 Lys
121 Gln
SECTION TWO
β-chains form a large intracellular pool and presumably aggregate to form βββββ4 molecules (tetramer) and called Hb-H.
HB-H disease is characterised by
• Moderate degree of haemolytic anaemia
• Red cell morphological appearance of thalassae- mia (see β-chain thalassaemia)
• Variable amount of Hb-H (usually 10–20%). Inclusion bodies: After incubation of blood sample with brilliant cresyl blue and then drawing a smear on the slide, when seen under microscope, numerous inclusion bodies can be seen which represent denatured Hb-H.
(b) Hb-Barts (γγγγγ4): In this the gross defect is in repression
of ααααα-chain synthesis resulting in great excess of γγγγγ- chains, which aggregate to γγγγγ4 molecules (tetramer).
Clinical Significance
Pregnant ladies suffering from this haemoglobinopathy delivers stillborn infants with clinical picture of Hydrops foetalis. This disorder is found in SE Asia. 80 per cent of stillborn infants are due to Hb-Barts.
(c) Hb-Portland (εεεεε2 γγγγγ2): In this ε chains and γ-chains are
produced in excess and can form ε2 γ2. Foetuses survive for some time by making increased amounts of embryonic Hb, but they commonly die before term or shortly after delivery (Hydrops foetalis).
2. βββββ-chain Thalassaemia (Thalassaemia Major)
When the thalassaemia gene represses β-chain synthesis, an excess of α-chains occur which can combine with δ-chains producing an increase in Hb- A2 or with γ-chains producing an increase in Hb-F.
This is the group of thalassaemias associated with severe anaemias of infancy or early childhood which was first described by Cooley, called Cooley’s anaemia. Infants suffering from this disease have Mongoloid features and have stunted growth. They suffer from severe haemolytic anaemia.
On examination: Marked pallor is seen; icterus is variable; enlargement of spleen (splenomegaly) is found.
Blood: Hb very low may be 3 to 5 Gm%; hypochromic microcytic anaemia; osmotic fragility increased.
Blood smear: Shows hypochromasia, polychromasia, baso- philic stippling, Target cells ++, nucleated cells +. Radiological examination: A lateral view of bones of skull shows hair-on-end appearance, a characteristic radio- logical finding.
Biochemically: Serum Fe level is normal. Rise in Hb-F- 5 to 80 per cent. Hb-A2 is significantly increased.
Note:β-thalassaemia is allelic with Hb-S or Hb-C, so that by interaction with the S or C gene there results a mixture of haemoglobins wherein S or C may comprise as much as 80 to 90 per cent of total Hb.
I. Questions (Essay type and short notes)
1. Write in detail the structure of Haemoglobin.
2. Describe mechanisms of CO2 transport in blood and the
role of Hb.
3. Give a brief account of chemistry of Hb and its properties. 4. What are different abnormal Haemoglobin and how they
differ from the normal haemoglobins? Short Notes
a. Abnormal Haemoglobins b. Functions of Hb
c. Role of Hb as a buffering agent d. Methaemoglobin
Differentiate
a. Carboxy-Hb and Carbamino-Hb b. Oxy-Hb and Carboxy-Hb c. Hb-A and Hb-F
d. Oxy-Hb and Methaemoglobin
II. MCQs (Give one correct answer)
1. Which is not a part of normal adult haemoglobin molecule? a. Vinyl group b. Ferric iron
c. Propionyl group d. Pyrrole rings e. Methylidene bridges
2. All of the following are associated with formation of methaemoglobinaemia, except:
a. Primaquin b. Acetanilid
c. Hb-M d. Methylene blue
e. Deficiency of methaemoglobin reductase
3. In sickle-cell Hb the position 6 of glutamyl residue of β- chain of normal adult Hb is replaced by:
a. Lysine b. Tyrosine
c. Valine d. Leucine
e. Glutamine
4. Which of the following statements about O2 binding and
release by Hb is correct?
a. O2 binding of any one of the four haemgroups occurs independently of the other three
b. Lowering the Ph accelerates the release of O2 from
Oxy-Hb
c. A high concentration of 2:3 BPG in the erythrocytes the binding of O2 by Hb
d. On binding O2 the iron of the haem is oxidised to ferric state
e. None of the above statement is correct
5. The most useful diagnostic test for CO poisoning is: a. Estimation of CO percentage in the environment b. Estimation of CO in expired air
c. Spectroscopy of blood of patient d. Measurement of respiratory rate e. Estimation of glucose in urine
SECTION TWO
6. The protective effect against malaria is related to which of the following?
a. Hb-F b. Hb-H
c. Bart’s Hb d. Hb-S
e. None othe above
7. One gram of Hb can carry how much oxygen?
a. 13.4 ml b. 1.34 ml
c. 11.34 ml d. 1.84 ml
e. 3.45 ml
8. Sickle cell anaemia is characterised by all of the following, except:
a. Presence of Hb-S b. Hyperbilrubinaemia c. Normocytic red blood cells d. Increased osmotic fragility e. Sickling of erythrocytes in vitro
9. Carbon monoxide inhibits mitochondrial electron transport by:
a. Inhibiting the electron transfer of NADH-Q reductase b. Binding to Hb in RB cells and so blocking the transport
of O2 to tissues
c. Binding to the O2 binding site of cytochrome oxidase
d. Blocking electron transport at the level of the cyt. b. → cyt.c1
e. Combining with coenzy-Q
10. Sickle cell anaemia is the clinical manifestation of homozygous genes for an abnormal Hb molecule. The mutational event responsible for mutation in the β-chain is:
a. Deletion b. Insertion
c. Point mutation d. Crossing over e. Non-dysjunction
11. The type of polypeptide chain present in globin of Hb-A2 are a. Two α-chains and two β-chains
b. Two α-chains and two γ-chains c. Two β-chains and two γ-chains d. Two α-chains and two δ-chains e. Two β-chains and two δ-chains
12. The incidence of salmonella infections is most often increased in patients with:
a. Sickle cell anaemia b. β-chain thalassaemia c. G-6 PD deficiency of RB cells d. Hereditary spherocytosis e. Hexokinase deficiency of RB cells 13. Which of the following statement is correct?
a. In Oxy-Hb formation Fe in haem is converted to ferric form
b. CO2 combines with haem to form carboxy-Hb
c. Co combines with NH2 group of Hb to form carbaminocompound
d. H2S combines with oxy-Hb to form sulfhaemoglobin
e. Fe in haem remains in ferrous form in methaemoglobin formation
14. In methaemoglobin formation, the iron in haem is in: a. Ferric form
b. Ferrous form
c. Both ferric and ferrous form d. All of the above
e. None of the above
15. The iron in haem is linked to the globin through:
a. Lysine b. Arginine
c. Valine d. Histidine
e. Glycine
16. Match the following:
a. Ferroprotoporphyrin b. Protoporphyrin IX c. Chlorophyll a d. Porphin
e. Ferriprotoporphyrin 1. Hemin ______________
2. A magnesium porphyrin derivative in which one pyrrole ring is partially reduced _________
3. Haem _____________
4. Derivatives are most important porphyrins in nature ___________
5. Basic structure from which Haemoglobin, cytochromes and chlorophyll are derived _________
17. The methylidene bridges of Fe porphyrin ring of haem molecule of Hb arises from:
a. The α-carbon of succinyl-CoA b. The carboxyl carbon of serine c. The β-carbon of serine d. The α-carbon of serine e. The carbon from CO2
18. Which of the following proteins associated with O2 is not a
haem-protein?
a. Peroxidase b. Superoxide dismutase
c. Catalase d. Cytochrome oxidase
e. Tryptophan pyrrolase
19. Cyanide is poisonous and lethal due to the fact, that it: a. Inhibits myoglobin of muscle
b. Combines with Rb cells membrane c. Forms a complex with Hb molecule
d. Inhibits cytochrome oxidase of electron transport chain e. Damages the brain cells
20. Match the following:
A. βs-chains B. γ-chains C. δ-chains D. ε-chains. 1. Haemoglobin A2 _________________ 2. Foetal Hb ________________ 3. Hemoglobin Gower _____________________ 4. Sickle cell Hb _______________ 21. Methaemoglobin contains: a. A denatured globin b. A ferroprotoporphyrin c. A ferriprotoporphyrin
d. A porphyrin with reduced methyne bridges e. None of the above
Answers to MCQs 1. b 2. d 3. c 4. b 5. c 6. d 7. b 8. d 9. c 10. c 11. d 12. a 13. d 14. a 15. d 16. 1-E, 2-C, 3-A, 4-B, 5-D 17. d 18. b 19. d 20. 1-C, 2-B, 3-D, 4-A 21. c.
Major Concepts
A. Define and classify vitamins. List all vitamins. Study fat soluble vitamins, their chemistry, functions, and deficiency disorders.
B. Study the dietary sources, important metabolites, metabolic functions and deficiency disorders of water soluble vitamins.
Specific Objectives
A. I. 1. Define and classify vitamins. There are four fat soluble vitamins A, D, E and K.
2. Study different forms of vitamin A, dietary sources and daily requirement.
3. Learn the various functions of vitamin A specially the visual cycle and deficiency manifestations.
II. 1. Study different forms of vitamin D and their synthesis specially calcitriol, the active form.
2. Learn the various functions of vitamin D and deficiency diseases.
III. 1. Study different forms of tocopherols (vitamin E), its absorption and transport.
2. Learn the various functions specially antioxidant property of vitamin E and deficiency manifestations.
IV. 1. Study different forms of vitamin K, list the dietary sources and daily requirement.
2. Study various functions of vitamin K specially in coagulation process and its deficiencies.
B. I. 1. There are two water-soluble vitamins—vitamin C and vitamin B complex groups.
2. Study the chemistry, dietary sources and absorption of vitamin C. Learn the various metabolic functions and fate of vitamin C,
specially its role in collagen synthesis.
3. Study deficiency manifestations of vitamin C.
II. 1. List all the vitamin B complex constituents.
2. Study the chemistry and “biological active” coenzyme form of each one of them.
3. List the dietary sources, daily requirement of each.
4. Study the metabolic role of each one of them and the deficiency manifestations.
III. Many vitamins manifest certain symptoms in case of excess intake. List and study them.
DEFINITION
Vitamins have been defined as organic compounds occurring in natural foods either as such or as utilisable precursors, which are required in minute amounts for normal growth, maintenance and reproduction, i.e. for normal nutrition and health.
1. They differ from other organic food stuffs in that:
• They do not enter into tissue structures, unlike proteins.
• Do not undergo degradation for providing energy unlike carbohydrates and lipids.
• Several B complex vitamins play an important role as coenzymes in several energy transformation reactions in the body.
2. They differ from hormones: In not being produced within the organism, and most of them have to be provided in the diet.
The protective substances present in milk were named as accessory factors by Hopkins. Almost in the same year, Funk (1911–12) isolated from rice polishings a crystalline substance which could prevent or cure polyneuritis in pigeons. Chemically it was found to be an amine and as it was vital to life, he named it as vitamine. Further developments in isolation and chemistry of vitamin have shown that only a few are amines. The term vitamin was retained, omitting the terminal “e” in its spelling.
Classification
All vitamins are broadly divided into two groups accord- ing to solubility. 1. Fat-soluble Vitamins • Vitamin A • Vitamin D