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BIOCHEMISTRY > WEEK 9 (Globular Proteins) > Flashcards

WEEK 9 (Globular Proteins) Flashcards

1
Q

What are Hemeproteins?

A

A group of specialised proteins containing Heme as a tightly bound prosthetic group

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2
Q

What is the role of the heme group based on?

A

Environ created by 3D structure of protein

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3
Q

Describe the structure

A
  • A complex of PROTOPORPHYRIN IX and Ferrous iron (Fe2+)
  • Iron is held in centre of heme molecule by bonds to 4 nitrogen of porphyrin ring
  • Heme Fe2+ can form 2 additional bonds, one on each side of the planar porphyrin ring
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4
Q

Give some examples of Heme functioning in proteins

A
  • Heme of a cytochrome functions as an electron carrier
  • Heme of catalase is part of the active site of the enzyme
  • In Hb and Myoglobin (the two most abundant heme proteins) heme serves to reversibly bind oxygen
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5
Q

Describe the structure and function of Myoglobin

A
  • functions as a reservoir for oxygen and acts as an oxygen carrier than increases rate of transport of oxygen within muscle cell
  • consists of a single polypeptide chain structurally similar to individual subunit polypeptide of Hb molecule, making myoglobin useful model for interpreting some complex properties of Hb
  • Myoglobin is a compact molecule (around 80% of its polypeptide is folded into 8 stretches of alpha-helix)
  • alpha-helical regions are terminated either by Pro (its 5-membered ring cannot be accommodated in alpha-helix) or by B-bends and loops stabilised by H-bonds and ionic bonds
  • interior is composed almost entirely of non-polar amino acids (packed together forming a structure stabilised by hydrophobic interactions)
  • charged amino acids located almost exclusively on surface, forming H-bonds with each other and with water
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6
Q

What is Myoglobin?

A

A hemeprotein present in heart and skeletal muscle

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7
Q

What are the key concepts behind the binding of heme group?

A
  • Heme group sits in a crevice lined with non-polar amino acids (except 2 His residues)
  • PROXIMAL HIS binds directly to iron of heme & DISTAL HIS does not directly interact with heme but helps stabilise binding of oxygen to ferrous iron
  • The protein/globin portion of myoglobin creates a MICROENVIRON (for heme this permits reversible binding of one oxygen molecule)
  • Simultaneous loss of electron by ferrous ion (oxidation) occurs only rarely
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8
Q

Where is haemoglobin exclusively found and what is its function?

A

Hb is found exclusively in Red blood cells & its main function is transport of oxygen from lungs to capillaries of tissues

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9
Q

Describe the structure of haemoglobin

A
  • HbA (major Hb in adults) is composed of 4 polypeptide chains, 2 alpha and 2 beta chains held together by non-covalent interactions
  • Each subunit has stretches of alpha-helical structure and a heme binding pocket
  • Tetrameric Hb is more complex structurally and functionally than myoglobin
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10
Q

Give examples of how Hb is more complex structurally and functionally than Myoglobin

A
  • Hb can transport CO2 from tissues to the lungs and carry O2 from lungs to cells of the body
  • Oxygen-binding properties of Hb are regulated by interaction with ALLOSTERIC EFFECTORS
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11
Q

Describe the quaternary structure of Hb

A
  • Hb tetramer is composed of 2 identical dimers (aB)1 and (aB)2
  • The 2 polypeptide chains in each dimer is held tightly together primarily by hydrophobic interactions
  • Ionic and hydrogen bonds occur between members of the dimer
  • The two dimers are held together primarily by polar bonds. The weaker interactions between the dimers allow them to move with respect to one another; this movement results in the two dimers occupying different relative positions in DEOXYHEMOGLOBIN as compared with OXYHEMOGLOBIN
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12
Q

What are the two forms of Haemoglobin and what are the differences between them?

A

T-form and R-form

T-FORM:
- deoxy form of Hb “T” or taut (tense) form
- the two alpha-beta dimers interact through a network of ionic and H-bonds which constraints movement of polypeptide chains
- low oxygen-affinity form of Hb

R-FORM:
- “R” or relaxed form
- binding of oxygen to Hb causes rupture of some the ionic and H-bonds between alpha-beta dimers which causes the polypeptide chains to have more freedom of moveemnt
- high oxygen-affinity form of Hb

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13
Q

Describe the binding of oxygen to myoglobin and Hb

A
  • Myoglobin can bind to 1 O2 molecules as it contains only 1 heme group
  • Hb can bind to 4 O2 molecules (one at each of its 4 heme groups)
  • Degree of saturation (Y) of these oxygen-binding sites on all myoglobin or Hb molecules can vary between 0 (all sites are empty) and 100% (all sites are full)
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14
Q

What is the Oxygen dissociation curve and what does it show?

A

The Oxygen dissociation curve is a plot of the degree of saturation (Y) measured at different PO2

what it shows:
- myoglobin has a higher oxygen affinity than Hb
- partial pressure of oxygen needed to achieve half-saturation of binding sites (P50) is around 1mm Hg for myoglobin & 26mm Hg for Hb
- the higher the oxygen affinity, the lower the pressure of oxygen needed to achieve half-saturation of binding sites

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15
Q

What bonds occur between aB dimer pairs in the deoxygenated state?

A

Weak ionic and hydrogen bonds

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16
Q

Describe the bonding between aB dimers in the oxygenated state

A

Some ionic and hydrogen bonds between aB dimers are broken in the oxygenated state

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17
Q

Describe the bonding that forms stable aB dimers

A

Strong interactions, primarily hydrophobic, between alpha and beta chains form stable aB dimers

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18
Q

When is the oxygen-dissociation curve steepest?

A

The oxygen-dissociation curve is steepest at the oxygen concentrations that occur in the tissues. This permits oxygen delivery to respond to small changes in pO2.

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19
Q

What are the key properties of the Myoglobin oxygen-dissociation curve?

A
  • HYPERBOLIC SHAPE which reflects that myoglobin reversibly binds a single molecule of oxygen
  • oxygenated (MbO2) and deoxygenated (Mb) exist in a simple equilibrium: Mb + O2 <–> MbO2
  • Mb is designed to bind oxygen released by Hb at the low pO2 found in muscles
  • Mb releases oxygen within muscle cell in response to oxygen demand
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20
Q

What are the key properties of the haemoglobin oxygen-dissociation curve?

A
  • SIGMOIDAL SHAPE which reflects that subunits cooperate in binding oxygen
  • although binding of 1st O2 is difficult, subsequent binding of O2 occurs with high affinity, shown by the STEEP UPWARD CURVE
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21
Q

What is heme-heme interaction?

A

Cooperative binding of oxygen by the 4 subunits of haemoglobin means binding of oxygen to one heme group increases the oxygen affinity of remaining heme groups in the same haemoglobin molecule

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22
Q

What affects the ability of haemoglobin to reversibly bind to oxygen?

A
  • pO2 (through heme-heme interaction)
  • pH of environ
  • pCO2 and availability of 2,3-biphosphoglycerate
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23
Q

What is the effect of Allosteric effectors?

A

Their interaction on one site on haemoglobin molecule affects binding of oxygen to heme groups at other locations on the molecule

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24
Q

Binding of oxygen to myoglobin is not influenced by allosteric effectors of Hb (TRUE/FALSE)

A

TRUE

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25
Q

Explain the sigmoidal oxygen-binding curve

A

Sigmoidal shape is due to the heme-heme interactions and reflects specific structural changes that are initiated at one heme and transmitted to other heme groups in Hb tetramer. The net effects is the affinity of Hb for the last oxygen is 300x greater than affinity for the 1st.

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26
Q

What does cooperative binding allow in tissues?

A

Cooperative binding of oxygen allows Hb to deliver more oxygen to tissues in response to relatively small changes in pO2

e.g
- in lungs, concentration of oxygen is high and Hb becomes saturated with oxygen
- in peripheral tissues, oxygen-haemoglobin releases much if its oxygen for use in oxidative metabolism

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27
Q

Describe the significance of the sigmoidal O2-dissociation curve and how a hyperbolic molecule differs

A

Steep slope of oxygen-dissociation curve over the range of oxygen concentration between lungs and tissues permits haemoglobin to carry and deliver oxygen efficiently from sites of high to sites of low pO2

A molecule with hyperbolic oxygen-dissociation curve (e.g myoglobin) would have max affinity for oxygen throughout this oxygen pressure therefore would deliver no oxygen to tissues

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28
Q

Describe what the Bohr effect is

A

The Bohr effect describes hemoglobin’s lower affinity for oxygen secondary to increases in the partial pressure of carbon dioxide and/or decreased blood pH

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29
Q

Explain the Bohr effect and what happens conversely

A

Release of oxygen from Hb is enhanced when pH is lowered or when Hb is in pressure of an increased pCO2. Both result in decreased oxygen affinity which shifts to the right in O2-dissociation curve

Conversel, raising pH or lowering concentration of CO2 results in a greater affinity for oxygen and a shift to the left in O2-dissociation curve

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30
Q

What does a decrease in pH result in?

A

decreased oxygen affinity of haemoglobin and therefore a shift to the right in the oxygen dissociation curve

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31
Q

At a lower pH, what is required to achieve any given oxygen saturation?

A

a greater pO2

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32
Q

What has a higher concentration of both CO2 and H+, capillaries or the lungs?

A

Capillaries

Concentration of both CO2 and H+ in capillaries of metabolically active tissues is higher than that observed in capillaries of lung, where CO2 is released into expired air

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33
Q

Explain the sources of protons that lower the pH

A
  • ORGANIC ACIDS (e.g lactic acid) are produced during anaerobic metabolism in rapidly contracting muscle
  • In tissues, CO2 is converted by CARBONIC ANHYDRASE to carbonic acid which spontaneously loses a proton becoming BICARBONATE (a major blood buffer). The proton produced contributes to lowering the pH.
34
Q

Explain how the differential pH gradient makes haemoglobin a more efficient transporter of oxygen

A

The differential pH gradient (lungs having higher, tissues lower pH) favours unloading oxygen in peripheral tissues and loading of oxygen in lung. Thus, oxygen affinity of haemoglobin responds to small shifts in pH between lungs and oxygen-consuming tissues, making Hb a more efficient transporter of oxygen.

35
Q

Describe the mechanism of the Bohr effect

A

Deoxy form of haemoglobin has a greater affinity for protons than oxy-Hb due to the IONISABLE GROUPS such as the N-terminal alpha-amino groups & specific side chains that have higher pKa’s in deoxy-Hb than in oxy-Hb. An increase in concentration of these protons causes these groups to become PROTONATED (charged) and able to form IONIC BONDS which stabilise the deoxy form of Hb, producing a decrease in oxygen affinity.

36
Q

Describe the equation of the Bohr effect

A

HbO2 (oxy-Hb) + H+ <-> HbH (deoxy-Hb) + O2

where an increase in protons (or a lower pO2) shifts equilibrium to the right, whereas an increase in pO2 (or decrease in protons) shifts equilibrium to the left

37
Q

What are the key properties of 2,3 bisphosphoglycerate?

A
  • 2,3 BPG is an important regulator of binding of oxygen to Hb
  • It is the most abundant organic phosphate in RBC where its concentration is similar to Hb
  • Synthesised as an intermediate of the glycolytic pathway
37
Q

What are the key properties of 2,3 bisphosphoglycerate?

A
  • 2,3 BPG is an important regulator of binding of oxygen to Hb
  • It is the most abundant organic phosphate in RBC where its concentration is similar to Hb
  • Synthesised as an intermediate of the glycolytic pathway
38
Q

What are the effects of 2,3 biphosphoglycerate on oxygen affinity?

A
  • 2,3 BPG decreases oxygen affinity of Hb by binding to deoxy-Hb but not to oxy-Hb (this binding stabilises the “taut” conformation of deoxy-Hb)
  • In RBC, presence of 2,3-BPG significantly reduces affinity of Hb for oxygen, shifting the oxygen dissociation curve to the right. This reduced affinity enables Hb to release oxygen efficiently at partial pressures found in tissues.
39
Q

What will a mutation in one of the residues of 2,3-BPG & deoxyhaemoglobin cause?

A

A mutation could result in Hb variant with abnormally high oxygen affinity

40
Q

Describe the binding between 2,3 biphosphoglycerate and deoxyhaemoglobin

A

A single molecule of 2,3-BPG binds to a positively charged cavity formed by two B-chains of deoxyhaemoglobin. The pocket contains several positively charged amino acids that form ionic bonds with the negatively charged phosphate groups of 2,3 BPG

41
Q

Hb from which ___________ is removed has a high affinity for oxygen

A

2,3-BPG

42
Q

Describe the importance of 2,3-BPG in chronic hypoxia and anemia

A
  • concentration of 2,3-BPG in RBC increases in response to chronic hypoxia (e.g in OBSTRUCTIVE PULOMONARY EMPHYSEMA or at high altitudes where Hb may have difficulty receiving oxygen
  • Intracellular 2,3-BPG elevated in chronic anemia since fewer RBCs are available to supply body’s oxygen needs
  • Elevated 2,3-BPG levels lower oxygen affinity of Hb allowing greater unloading of oxygen in capillaries of tissues
43
Q

Explain the role of 2,3 BPG in transfused blood

A

2,3 BPG is essential for normal oxygen transport function of Hb

Storing blood in acid-citrate-dextrose causes a decrease of 2,3 BPG in RBCs. This blood displays an abnormally high oxygen affinity and fails to unload its bound oxygen properly in the tissues. Hb deficient in 2,3 BPG thus acts as an oxygen “trap” rather than as an oxygen transport system.

44
Q

What are the statistics of transfused blood with depleted supplies of 2,3 BPG?

A

Transfused RBCs are able to restore depleted supplies of 2,3 BPG in 24-48h. However, severely ill patients may be seriously compromised if transfused with large quantities of such 2,3 BPG stripped blood

45
Q

How can a decrease in 2,3 BPG be prevented?

A

A decrease in 2,3 BPG can be prevented by adding substrates to the storage medium (e.g inosine (hypoxanthine-ribose))

Inosine (an uncharge molecule) can enter red blood cells, release its ribose moiety, become phosphorylated and enter hexose mosophosphate pathway and eventually be converted to 2,3 BPG

46
Q

What are the key components of the binding of CO2?

A
  • Most CO2 produced in metabolism is hydrated and transported as BICARBONATE ION
  • Some CO2 is carried as CARBAMATE bound to uncharged alpha-amino groups of Hb (CARBAMINO-HB)
  • Binding of Co2 stabilises T (taut) or deoxy form of Hb, resulting in decrease in its affinity for oxygen. In lungs, CO2 dissociates from Hb released in breath
47
Q

What are the key components of the binding of CO?

A
  • CO binds tightly (but reversibly) to Hb iron forming CARBON MONOXYHEMOGLOBIN (HbCO)
  • When CO binds to one or more of the 4 heme sites, Hb shifts to the relaxed conformation, causing remaining sites to bind oxygen with high affinity
  • Oxygen saturation curve shifts to the left and changes the normal sigmoidal shape towards a HYPERBOLA which results in affected Hb unable to release oxygen to the tissues
  • Affinity of Hb to CO is 220x greater than for oxygen
48
Q

What does CO toxicity result from and how is it treated?

A

CO toxicity appears to result from a combination of tissue hypoxia and direct CO-mediated damage at cellular level

CO poisoning is treated with 100% oxygen therapy which facilitates dissociation of CO from Hb

49
Q

When are HbF and HbA2 synthesised?

A

HbF are normally synthesised only during foetal development & HbA2 are synthesised in adulthood at low levels compared to HbA

50
Q

How can HbA become modified?

A

HbA can be modified by covalent addition of a hexose

51
Q

What is Fetal haemoglobin (HbF) and how is it synthesised during development?

A

HbF is a tetramer of two a plus two y chains. y chains are members of B-globin gene family.

HbF synthesis during development
- In first few weeks after conception, embryonic Hb (Hb Gower 1) composed of 2 ZETA and 2 EPSILON chains are synthesised by EMBRYONIC YOLK SAC
- Within a few weeks, FOETAL LIVER begins to synthesise HbF in developing BONE MARROW

HbF is the major Hb found in foetus and newborn accounting for around 60% of total Hb in RBCs during the last months of foetal life. HbA synthesis starts in bone marrow at about the 8th month of pregnancy and gradually replaces HbF.

52
Q

Describe the key components of 2,3 BPG binding to HbF

A
  • Under physiologic conditions, HbF has a higher affinity for oxygen than HbA, as a result HbF’s binding to 2,3 BPG is weak
  • The y-globin chains lack some of the positively charged amino acids responsible for binding 2,3 BPG in B-globin chains
  • 2,3 BPG serves to reduce affinity of HbA for oxygen, weaker interaction between 2,3 BPG and HbF results in higher oxygen affinity for HbF relative to HbA
  • If both HbF and HbA are stripped of their 2,3 BPG they then have similar affinity for oxygen
53
Q

What does the higher oxygen affinity of HbF facilitate?

A

Transfer of oxygen from maternal circulation across placenta to RBCs of foetus

54
Q

What is HbA2?

A

HbA2 is a minor component of normal adult Hb appearing around 12 weeks after birth (around 2% of total Hb is composed of this)

55
Q

What is HbA1c?

A

Under physiologic conditions, HbA is slowly & non-enzymatically glycosylated and the extent of glycosylation is dependent on the plasma concentration of a particular hexose

HbA1c is the most abundant form of glycosylated Hb and has glucose residues attached predominantly to NH2 groups of the N-terminal Val of B-globin chains

56
Q

Where are increased amounts of HbA1c found?

A

In RBCs of diabetes mellitus ad their HbA has contact with higher glucose concentrations during the lifetime of these cells

57
Q

Describe the organisation of global genes in the alpha-gene family

A
  • Genes for alpha and beta global like subunits of Hb chains occur in 2 separate gene clusters (families) located on 2 different chromosomes
  • a-gene cluster on chromosome 16 contains 2 genes for alpha-globin chains. It also contains ZETA GENE expressed early in development as a component of embryonic Hb and a number of global-like genes that are not expressed (PSEUDOGENES)
58
Q

Describe the organisation of global genes in the beta-gene family

A

A single B-globin gene located on chromosome 11 plus 4 B-globin-like genes (EPSILON GENE ε, two GAMMA GENES γ and the δ gene that codes for the global chain found in minor adult HbA2)

59
Q

Two copies of the alpha-globing gene are designated a1 and a2 on chromosome _____

A

16

60
Q

What are Hemoglobinopathies?

A

A family of disorders caused by the production of structurally abnormal Haemoglobin, synthesis of insufficient quantities of normal haemoglobin, or rarely both

61
Q

What are examples of Hemoglobinopathies?

A
  • Sickle-cell anaemia (HbS)
  • Hb C disease (HbC)
  • Thalassemia syndromes
62
Q

What are the differences in the causes of HbS, HbC & Thalassemia?

A

HbS & HbC result from altered amino acid sequences whereas Thalassemia is caused by decreased production of haemoglobin

63
Q

What is Sickle-cell anaemia?

A

A genetic disorder of blood caused by a single nucleotide alteration (POINT MUTATION) in the B-globin gene. It is a homozygous recessive disorder and occurs in individuals who inherit 2 mutant genes that code for β-chains. Mutant β-globin chain = βS, resulting Hb = α2βS2 -> HbS

SYMPTOMS:
- lifelong episodes of pain “crises”
- chronic haemolytic anaemia
- increased susceptibility to infections (beginning in early childhood)
- acute chest syndrome
- stroke
- splenic & renal dysfunction

Amino acid substitution exchanges Glutamate to Valine in position 6

64
Q

What are the statistics of Sickle cell anaemia?

A
  • Most common inherited blood disorder in the US affecting around 80,000 (primarily African-Americans)
  • Affects 1/500 newborn infants
  • Lifetime of an erythrocyte homozygous for HbS is around 20 DAYS compared to 120 DAYS for normal RBCs
  • 1/10 African-Americans are heterozygotes (one normal and one sickle cell gene)
65
Q

Describe heterzygotic individuals for Sickle-Cell anaemia

A

Heterozygotes contain both HbS and HbA. These individuals have the SICKLE CELL TRAIT therefore they usually do not show clinical symptoms and can have a normal life span

66
Q

Describe how Electrophoresis is used to diagnose Sickle-cell anaemia

A

During Electrophoresis at alkaline pH, HbS migrates more slowly towards the anode than HbA due to the absence of the negatively charged Glutamate residues in the 2 β-chains. This shows that HbS is less negative than HbA.

Electrophoresis of Hb from lysed RBC is routinely used in diagnosis of sickle cell trait & sickle cell disease

67
Q

Are Haemoglobins negatively or positively charged?

A

Haemoglobins are negatively charged and migrate towards the anode

68
Q

Describe how Sickle cell-anaemia causes tissue anoxia

A
  • Substitution of non-polar Valine for a charged Glutamate forms a PROTRUSION on the or a charged Glu forms a protrusion on the β-globin that fits into a COMPLEMENTARY SITE on the alpha-chain of another Hb molecule in the cell
  • At low oxygen tension, HbS POLYMERISES inside RBCs first forming a GEL then assembling into a network of FIBROUS POLYMERS that STIFFEN and DISTORT the cell producing rigid, misshapen RBCs
  • These sickled cells frequently block the flow of blood in narrow capillaries. This interruption in the supply of oxygen leads to LOCALISED ANOXIA (oxygen deprivation) in the tissue leading to pain and eventually death (INFARCTION) of cells in the vicinity of blockage
69
Q

What are some variables that increase sickling?

A

enhanced by any variable that increases proportion of HbS in its deoxy state (e.g reduces affinity of HbS for oxygen)

  • decreased oxygen tension (high altitude or flying in non-pressurised plane)
  • increased pCO2
  • decreased pH
  • increased concentration of 2,3 BPG in RBCs
70
Q

What is the treatment for Sickle-cell Anaemia?

A
  • Adequate hydration
  • Analgesics
  • Aggressive antibiotic therapy (if infection present)
  • Tranfusions for fatal vasocclusions
  • Intermittent transfusions with packed RBCs
  • Hydroxyurea (ANTI-TUMOR DRUG) decreases frequency of painful crises & reduces mortality
71
Q

What is the mechanism behind Hydroxyurea?

A

Mechanism is not fully understood but may include a modest increase in Foetal Hb which decreases sickling

72
Q

What are the pros and cons of Intermittent transfusions?

A

Intermittent transfusions with packed RBCs reduce risk of stroke, but benefits must be weighed against complications of transfusion, which include iron overload (hemosiderosis), blood-borne infections, and immunologic complications.

73
Q

What is the possible advantage of Sickle-cell cells?

A

heterozygotes for sickle cell gene are less susceptible to malaria, caused by Plasmodium falciparum, which spends part of its life cycle in RBC. As RBCs in heterozygotes, like those in homozygotes, have shorter lifespan than normal, parasite cannot complete the intracellular stage of its development. This may provide selective advantage to heterozygotes living in regions where malaria is a major cause of death.

74
Q

What is Haemoglobin C disease?

A

A hemoglobinopathy caused by a single amino acid substitution in the 6th position of the β-globin chain where a Glutamate is substituted for a Lysine. This substitution causes HbC to move more slowly towards the anode than HbA or HbS (Lysine is more +ve).

Patients homozygous for HbC generally have mild, chronic hemolytc anemia, do not suffer from infarctive crises, and no specific therapy is required

75
Q

What is Haemoglobin SC disease?

A

In Haemoglobin SC disease some β-globin chains have sickle cell mutation whereas other β-globin carry the mutations found in HbC disease (compound heterozygotes)

  • Hb levels tend to be higher in HbSC disease than in sickle cell disease and may even be at low end of normal range
  • Patients generally have painful crises beginning in childhood
  • It is common for patients with HbSC to remain well and undiagnosed until they suffer INFARCTIVE CRISIS which often follows CHILDBIRTH or SURGERY and may be fatal
76
Q

What are Methemoglobinemias?

A

Oxidation of heme component of Hb to ferric (Fe3+) state forms METHEMOGLOBIN which cannot bind oxygen. This oxidation may be caused by the action of certain drugs or from inherited defects or from deficiency of NADH-cytochrome b5 reductase (aka NADH MEHEMOGLOBIN REDUCTASE) which is an enzyme responsible for the conversion of Methemoglobin (Fe3+) to Hb (Fe2+) resulting in the accumulation of HbM

77
Q

Why are newborns more susceptible to effects of HbM than adults?

A

Since RBCs of newborns have one-half capacity of adults to reduce HbM

Newborns are particularly susceptible to effects of HbM-producing Cephalopelvic disproportion

78
Q

What are the signs and symptoms of Methemoglobinemias?

A
  • “chocolate cyanosis” (a brownish blue coloration of skin and membranes)
  • chocolate coloured blood due to dark coloured HbM
  • tissue hypoxia
  • anxiety
  • headache
  • dyspnea
  • coma
  • death
79
Q

What is the cause of Thalassemias?

A

In Thalassemia, synthesis of either β- and a-globin chains is defective due to a variety of mutations including gene deletions, substitution or deletion of one of the many nucleotides in DNA

Each Thalassemia can be classified as a disorder with no global chains produced (βº- or αº- thalassemia) or one in which some synthesised but at reduced rate (β+- othalassemiar α+-)

80
Q

Describe what B-Thalassemia is and its effects

A

Synthesis of β-globin chains decreased or absent, whereas α-globin chains synthesis is normal

α-globin chains cannot form stable tetramers and precipitate therefore premature death of cells initially destined to become mature RBCs

There are only 2 copies of β-globin genes -> individuals with β-globin gene defects have either β-thalassemia trait (β-thalassemia minor) if only one copy defective, or β-thalassemia major if both genes are defective

81
Q

What is a-thalassemia?

A

Synthesis of α-globin chains is decreased or absent. A loss of alpha chains is fatal since a mutated haemoglobin can cause serious defects such as inhibited foetal development.

BIOCHEMISTRY (12 decks)

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