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Biochemistry > Chapter 10 Haemoglobin And Porphyrins > Flashcards

Chapter 10 Haemoglobin And Porphyrins Flashcards

1
Q

Haemoglobin is a tetrameric allosteric protein . What does it mean??

A

A tetrameric allosteric protein refers to a protein that consists of four subunits and exhibits allosteric regulation.

Allosteric regulation means that the binding of a molecule to one site on the protein can affect the activity or function of another site on the protein.

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2
Q

Normal conc. of heme in males and females?
Molecular weight of hemoglobin and myoglobin?

A

In males:
14-16g/fdl

In females:
13-15g/dl

Molecular weight:
Hemoglobin-64,450
Myoglobin-17,000

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3
Q

Haem contain globin, the ____ part and heme the ____ part?

A

Globin - apoprotein
Heme - non-protein (prosthetic group)

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4
Q

Globin consists of _____ polypeptide chains?
In adult hemoglobin HbA1?
Number of amino acids?

A

4;
•2- alpha chains —141 amino acids
•2- beta chains—-146 amino acids

Total Amino acids in HbA1;
574

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5
Q

The 4 subunits of hemoglobin ar held together by?

A

Non-covalent interactions:
Hydrophobic
Ionic
Hydrogen bonds

Each subunit has a heme group

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6
Q

Structure of heme?

A

protoporhyrin IX
A Porphyrin molecule with iron at centre.

Protoporphyrin consists of;
4 pyrrole rings
To which, are attached:
1. 4 methyl
2. 2 proponyl
3. 2 vinyl groups

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7
Q

Heme is a common prosthetiv group present in cytochromes in certain enzymes eg?

A

1.Catalase
2.Tryptophan pyrolase
3.Chlorophyll (Mg2+)

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8
Q

About 80% of heme syntheis occurs in?
And the remaining in?

A
  1. Erythroid precursor cells in bone marrow
  2. Liver
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9
Q

What are erythroid cells?

A

Erythroid cells are the precursor cells that develop into erythrocytes, which are mature red blood cells.

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10
Q

Why mature erythrocytes don’t synthesize heme?

A

Because they dont have mitochondria or nucleus

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11
Q

Heme synthesis occurs in mitochondria or cytosol?

A

Partly in both:
1st step: ALA synthesis in —mitochondria
And last 3 steps: involving oxidase enzymes—–mitochondria

Rest in: cytosol

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12
Q

What are the 4 major most important events in heme synthesis?

A
  1. Porphobilinogen synthesis (PBG)
  2. PBG —–to—- uroporphyrinogen
  3. Uroporphyrinogen —-to— protoporphyrinogen IX
  4. Incorporation of iron
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13
Q

Pnemonic for steps of heme synthesis?

A

Some. Great.
Doctors
Palpate
Heart
Under
Cover
Produce
Pure
Heme

Succinyl coA + Glycine
|. (ALA synthase)
D-ALA
|. (ALA dehydratase)
|
Porphobilinogen
| (U synthase-I)
|
Hydroxymethylbilin
| (U synthase-III)
|
Uroporphyrinogen-III
|. (U decarboxylase)
|
Coroporphyrinogen-III
| (Co-oxidase)
|
Protoporhyrinogen-IX (III)
| (Pro- oxidase)
|
Protoporphyrin
| (ferrochelatase)
|
Heme

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14
Q

1.The coenzyme for ALA synthase in the 1st step for heme synthesis is?

  1. ALA synthase is inhibited by?
A

1.Pyridoxal phosphate (PLP)

  1. Lead
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15
Q

Deficiency of enzymes ALA synthase and ALA dehydrogenase lead to?

A

Anemia

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16
Q

1.Deficiency of enzyme uroporphyrinogen-I synthase leads to?

  1. Treated by?
  2. Caution?
A

1.Acute intermittent porphyria

  1. Administration of hematin (inhibits enzyme ALA synthase and the accumulation of PBG)
  2. Avoid drugs (e.g, barbiturates) that induce synthesis of **cytochrome P450)—– due to increased activity of ALA synthase —— accumulation of PBG +ALA
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17
Q

Congenital eryhthropoeitic porphyria is caused due to deficiency of which enzyme?

A

Uroporphyrinogen-III synthase

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18
Q

Deficiency of enzyme Uroporphyrinogen decarboxylase leads to?

A

Porphyria Cutanea Tarda

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19
Q

Which is the most common porphyria?

A

Porphyria cutanea tarda

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20
Q

Deficiency of enzyme coproporphyrinogen oxidase leads to?

A

Heridity coproporphyria

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21
Q

Deficiency of protoporphyrinogen oxidase leads to?

A

Variegate porphyria

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22
Q

Deficiency of ferrochelatase leads to?

A

Protoporhyria also known as erythropoietic protoporphyria

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23
Q

What is porphyria?

A

Porphyrias are a group of rare genetic disorders that affect the production of heme, a component of hemoglobin.
-enzymes that code for heme synthesis are affected
- characterized by increased exctertion of porphyrins or porphyrin precusors

. It can cause a variety of symptoms, including ;
•abdominal pain,
•skin sensitivity to sunlight,
•neurological issues,
• psychiatric symptoms.

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24
Q

Porphyrias are either inherited or acquired, classified into?

A

2 categories;
1.Erythropoetic
Enzyme deficiency in eryhthrocytes

2.Hepatic
Enzyme defect in liver

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25
Q

All porphyrias are Autosomal dominant disorders, except?

A

Congenital eryhthropoetic porphyria ( autosomal recessive)

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26
Q

What is meant by autosomal dominant disorders?

A

Autosomal (defects on genes which are present on non-sex chromosome——-can be inherited from both parents equally) dominant disorders are genetic conditions caused by a mutation in one copy of a gene. These disorders can be passed down from one generation to the next and can be expressed even if only one copy of the gene is affected.

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27
Q

Disorder due to deficiency of ALA synthase?

A

X-linked sideroblastic anemia

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28
Q

What are the 6 porphyrias?

A

Hepatic
1. Acute intermittent (U- I synthase)
2. Porphyria cutanea tarda (U-decarboxylase)
3. Heriditary coproporphria (Coproporphyrinogen oxidase)
4. Variegate porphyria (Protoporphyrinogen oxidase)
Erythropoeitic
4.Congenital eryhthropoeitic porphyria (U-III cosynthase)
5.Protoporphyria (eryhthropeitic protoporphyria) (ferrochelatase)

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29
Q

Why neuropsychiatric disturbances occur in acute intermittent porphyria?

A

Due to reduced activity of Tryptophan pyrrolase (due to low heme level) ——- accumulation of tryptohan & 5-hydroxytryptamine

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30
Q

1.In acute intermittent porphyria, there is increased excretion of?
2. And the urine of patient gets darkened on exposure to air due to?
3. When It is usually expressed?

A
  1. Porphobilinogen and d-Aminolevulinate (PBG & ALA)
  2. Conversion of porphobilinogen to porphobilin and porphyrin
  3. After puberty
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31
Q

Why patients of acute intermittent porphyria Not photosensitive?

A

Because the enzyme defects occur prior to formation of uroporphyrinogen

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32
Q

What are the main symptoms of acute intermittent porphyria?

A
  1. Abdominal pain
  2. Neuropsychiatric symptoms
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33
Q

All 6 types of porphyrias have photosensitivity as their symptom except?

A

Acute intermittent porphyria

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34
Q

Which disease is also known as vampire/were wolves disease? And why?

A

Porphyria—-causes photosensitivity

When block is below uroporphyrinogen

Uroporphyrinogen—- converts into porphyrin rings—- Under UV light—- excited—- Reactive oxygen spaces are created—- lysosomal damge—-lysosomal enzymes—– skin lesion—- disfigured face (werewolf/vampire appearance)

Patient of Congenital erythropoeitic porphyria & Porphyria cutanea Tarda show fluorescent appearance of teeth under UV rays —-Eryhthrodontia( red or reddish-colored teeth)

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35
Q

Photosenisitivity is due to accumulation of?

A

Porphyrins

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36
Q

Symptoms of congenital erythropoeitic porphyria?

A

1.Increased hemolysis
2. Photosensitivity

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37
Q

Porphyria cutanea tarda is also known as?

A

Cutaneous hepatic porphyria

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38
Q

1.________ is the most common clinical manifestation of porphyria cutanea patients?
2. _____ exhibits fluorescence due to concentration of accumulated porphyrins
3. Increased excretion of ____?

A
  1. Cutaneous photosensitivity
  2. Liver
  3. Uroporphyrins I & III
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39
Q

Patients of which porphyria show the same clinical manifestations as in acute intermittent porphyria?

A

Heriditary coproporphyria
(Abdominal pain, neuropsychiatric symptoms, photosensitivity)

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40
Q

Reticulocytes (young RBC) and skin biopsy show red fluorescence in which porphyria?

A

Protoporphyria

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41
Q

_________ accumulates in tissues and is excreted in urine & faeces in protoporphyria?

A

Protoporphyrin IX

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42
Q

All the intermediates accumulate in body and are excteted in ?

And which intermediates is not produced due to deficency of protoporphyrinogen oxidase?

A

Variegate porphyria

Protoporphyrin IX

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43
Q

Acquired (toxic) porphyrias is due to exposure of body to.

A
  1. Heavy metals —- e.g lead
  2. Toxic compounds— hexochlorobenzene
  3. Drugs—- e.g griseofulvin
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44
Q

1.Administration of ______ can be used in the treatment of certain cancers by phototherapy?
Why?
2.Cancer phototherapy is mostly carried out by adminsitering____?

A

1.Porphyrins bcz tumor take up more porphyrins than normal tissues
When tumor exposed to argon laser—— porphyrins get excited—- produce cytotoxic effect on tumor cells

  1. Hematoporphyrin
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45
Q

ALA dehydratase is a _____ containing enzyme?

A

Zinc

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46
Q

The 4 pyrrole rings in porphyrins are interconnected by ______ bridges derived from a-carbon of glycine

A

Methylene -CH2-

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47
Q

The activity of ALA synthase is ______ by administration of drugs? Name those drugs that are metabolized by heme containing protein cytochrome P450?

And why?

A
  1. Increased
    (Phenobarbital, insectiside & carcinogen)
  2. Bcz on administration, the heme level decreases as heme gets incorporated in Cytochrome, so ALA synthesis increases
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48
Q

Porphyrins are cyclic compounds composed of ____ p
rings held together by ____ bridges

  1. Heme is an _____-containing porphyrin
    Chlorophyll is a________ containing porphyrin
A
  1. 4 pyrrole rings
  2. Methylene bridges
  3. Iron
  4. Mg+2
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49
Q

What are the types of porphyrins?

A
  1. Type I Porphyrins
    When substituent group on 8 positions—–symmetrical

2.Type III Porphyrins
When substituent group on 8 positions—–asymmetrical
-more common
-Type IX porphyrins
E.g Uroporphyrin-III
— order of substituent group is revered (P,A instead of A,P)

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50
Q

1.About ______ g of hemoglobin is broken down per day and resynthesized?
2. Life span of erythrocytes?

A

1.6g

  1. 120 days
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51
Q

About ______% heme for degradation comes for erythrocyes, and rest of ____ from immature RBCs, myoglobin and cytochromes?

A
  1. 80%
  2. 20%
52
Q

1._________ microsomal enzyme cleaves the methyl bridges between 2 pyrrole rings (A & B) to form_____?
2.And it utilizes?

  1. Name the products of this reaction?
A
  1. Heme oxygenase
    Forms bilivirdin
  2. NADPH & O2
  3. Products are;
    •. Biliverdin (green pigment)
    •. Fe+3 (ferric)
    •. Carbon monoxide (CO)
53
Q

Biliverdin is excreted in ______& _____ but in ____ it is further degraded?

A
  1. Birds & amphibians
  2. Mammals
54
Q

Biliverdin (green) is converted to bilirubin (yellow) by an enzyme?

A

Biliverdin reductase

55
Q

1.1 g of Hb on degradation finally yields about _____ mg bilirubin?

  1. About ______ mg of bilirubin is daily produced in human adults?
A

1.35 mg
2. 250–350 mg

56
Q

Bilirubin is ______ so insoluble in aqueous sol

A
  1. Lipophilic
57
Q

Bilirubin is transported to liver in the plasma in a _______ bound form to ______?

A

Non-covalently bound form to albumin

58
Q

Albumin has how many binding sites and for what?

A

2 binding sites for bilirubin;
High affinity site
About 25mg of bilirubin can bind tightly to albumin at this site

Low affinity site
Rest of bilirubin binds loosely to this site

59
Q

Which drugs and antibiotics can displace bilirubin from albumin , so that it enters CNS & cause damage to neuron?

A

E.g Sulfonamides
Salicyclates

60
Q

As albumin-bilirubin complex enters the liver, bilirubin dissociates and is taken up by_____ by a carrier mediated active transport, and inside, it binds to a specific intracellular protein called ______?

A
  1. Hepatocytes
  2. Ligandin
61
Q

1.Conjugation of bilirubin occurs in?
2.And by what molecules, supplied by what?
3.And catalyzed in the presence of which enzyme (from where)?
4. Product of conjugation?

A

1.Liver

2.By 2 molecules of glucoronate supplied by 2UDP-glucoronate

3.bilirubin glucoronyl transferase (of SER)

  1. Water-soluble bilirubin diglucoronide
62
Q

The enzyme bilirubin glucoronyl transferase can be induced by number of drugs e.g?

A

Phenobarbital

63
Q

Almost all the bilirubin ( greater than 98%) enters the bile in which form?

A

Conjugated form (bilirubin diglucoronide)

64
Q

Transport of bilirubin diglucuronide to bile is an active, energy dependant process and rate ______ process?

A

Rate limiting

65
Q

1.Deconjugation of bilirubin diglucuronide occurs in?

  1. By which enzyme?
  2. Product?
A
  1. Intestine
  2. B-glucoronidases
  3. Bilirubin
66
Q

Bilirubin in the intestine is converted into _______ and which is then converted to _______ in kidney?

A
  1. Intestine—–urobilinogen(colorless)
  2. Kidney—–urobilin(yellow)
67
Q

In kidney , a major part of urobilinogen is converted by bacteria to ______ which is excreted along with faeces?

A

Stercobilin

68
Q
  1. Yellow colour of urine is due to _____
  2. Brown colour of faeces is due to ______?
A

1.Urobilin — urine
2. Stercobilin—- faeces

69
Q

Brief process of degradation of heme to bile pigments?

A

Aged eryhthrocytes ( attacked by macrophages)
|
Haem + globin-(amino acids utilized or degraded)
|
Haem
| (heme oxygenase)

Biliverdin
| (biliverdin reductase)

Bilirubin
|

Bilirubin-albumin complex
(In blood)

Bilirubin (in liver)
| (Bilirubin glucoronyl transferase)

Bilirubin diglucoronide(–to–bile)
| (Microbial enzymes)

Urobilinogen (intestine)
| (Microbial enzymes)
|_______________
(Kidney) |
Urobilin. Stercobilin
|. |

(Urine) (faeces)

70
Q

Normal serum total bilirubin conc. is in the range of?

A

0.2 —– 1.0 mg/dl
0.2—0.6——–unconjugated
0.2—0.4——–conjugated

71
Q

Jaundice is caused by deposition of _______?
The term _______ is used to represent its increased conc in serum?

A
  1. Bilirubin
  2. Hyperbilirubinemia
72
Q
  1. Jaundice is also known as?
  2. It’s a _____ rather than a disease?
A
  1. Icterus
  2. Symptom
73
Q

Classification of jaundice?
And characteristics?

A

3 major types;

  1. Hemolytic

-increased hemolysis of erythrocytes
-(e.g in
•Incompatible blood transfusion
•Malaria
•Sickle cell anemia
(Characteristics)
•Serum Unconjugated bilirubin increase
•Increased urobilinogen in urine
•High stercobilinogen in faeces

  1. Hepatic

-liver dysfunction (parenchymal cell damage)
-due to
•Viral hepatitis (most common)
•Poisons & toxins
•Cardiac failure
(Characteristics)
•Dark urine (excess urobilinogen)
•Pale stools(absent stercobilin)
•Nausea & anorexia
•Increased activities of alanine transaminase & aspartate transaminase due to damage to hepatocytes
• increased conjugated & unconjugated bilirubin

  1. Obstructive/regurgitation
  • obstruction in bile duct
    (Prevents passage of bile —- intestine)
    Due to gall stones (in gall bladder made up of cholesterol or bilirubin)
    Or tumors
    (Characteristics)
    •Increased conjugated bilirubin in serum
    •Increased serum alkaline phosphastase
    •Dark urine (high urobilinogen)
    •Clay coloured faeces (absent
    Stercobilinogen)
74
Q

Normal bilirubin production of is _____g/day
And liver has a capacity to conjugate ______ g bilirubin per day?

3.What happens to liver capacity in hemolytic jaundice?

A
  1. 0.3g/day
  2. 3.0g/day
  3. Over production of bilirubin- more than liver can conjugate
75
Q

What is blood-brain barrier?

A

The blood-brain barrier is a protective barrier formed by specialized cells in the blood vessels of the brain. It helps regulate the passage of substances from the bloodstream into the brain and protects the brain from harmful substances.

76
Q

Neonatal-physiological jaundice occurs due to the low activity of _______ enzyme in newborn?
Other causes?

  1. Results in?
A

UDP-glucoronyl transferase activity is low

•Unavailabilty of substrate UDP-glucoronic acid for conjugation
• immature hepatic system (so no conjugation of bilirubin)

  1. Hyperbilirubinemic toxic encephalopathy or kernicterus that causes mental retardation.
77
Q

What is kernicterus?

A

Kernicterus or hyperbilirubinemic toxic encephalopathy is a condition that occurs when there is a buildup of bilirubin in the brain, leading to neurological damage. (Breaking blood brain barrier—– bilirubin moves from blood stream to brain tissues).

It can result from severe jaundice in newborns. neonatal-physiological jaundice

78
Q

The drug used for treatment of neonatal jaundice?

A

phenobarbital (induce bilirubin metabolism enzymes in liver)

79
Q

Bilirubin can absorb ____ light of wavelength?

A

Blue light (420-470nm)

80
Q

_______ bilirubin is more toxic

A

Unconjugated

81
Q

In phototherapy,
When jaundiced neonates are exposed to blue light what happens?

A

The toxic unconjugated bilirubin gets converted into non-toxic isomer —lumirubin
By a process called photoisomerization

  • lumirubin can be easily excreted by kidneys (despite being unconjugated whereas bilirubin can’t)
82
Q

What is Crigler najjar syndrome?
Types?

A

Crigler-Najjar syndrome is a rare genetic disorder where the liver is unable to properly process bilirubin, leading to high levels of bilirubin in the blood.
It can cause severe jaundice and may require treatment such as phototherapy or liver transplantation.

There are two types of Crigler-Najjar syndrome:
type 1 and type 2.
Type 1
-more severe
-defect in hepatic enzyme—UDP glucoronyl transferase

Type-2
-is less severe
-serum bilirubin conc. less than 20mg/dl
-defect in hepatic enzyme—UDP glucoronyl transferase

83
Q

Crigler-Najjar syndrome Type-I is also known as?

A

Congenital non-hemolytic jaundice

84
Q

_______ is a combination of disorders including;
Defect in bilirubin uptake by hepatocytes,
Conjugation defect
Decreased hepatic clearance of bilirubin?

A

Gilberts disease

85
Q

Bilirubin is known to function as an?

A

Antioxidant

86
Q

________ is used to control neonatal physiological jaundice?

A

Phototherapy (exposure to blue light)

87
Q

1.In adults small conc. (Less than 5%) of hemoglobin______ is present?

  1. _____ Hb formed by covalent bonding of glucose is increased in diabetes mellitus?
  2. What is heredity persistence of fetal hemoglobin?
A

1.HbA2

  1. Glycosylated hemoglobin HbA1C
  2. In which fetal hemoglobin synthesis is not terminated & continues into adulthood
88
Q

1.Composition of hemoglobin (chains)?
HbA1
HbA2
HbF (fetal hemoglobin)
HbA1c (glycosylated Hb)

  1. Their percentages?
A

Chains
•HbA1—-2a +2B (alpha & beta)
•HbA2—2a + 2d (alpha & delta)
•HbF—2a + 2y (alpha & gamma)
•HbA1c—2a + 2B -glucose

Percentages;*
HbA1—-95%
HbA2—–<5%
HbF (fetal hemoglobin)—–<2%
HbA1c (glycosylated Hb)—–<5%

89
Q

Hemoglobin consists of ____ polypeptide chains but myoglobin consits of?

  1. Total amino acids in myoglobin polypeptide chain?
  2. Myoglobin is a monomeric _____binding heme protein?
A
  1. 4 polypetide
    . Single polypeptide
  2. 153 amino acids
  3. Oxygen binding
90
Q

Myoglobin is an early marker for ?

Cause of Myoglobinuria in adults & children?

________ serves as a reservior for oxygen?

A

1.Myocardial infarction.

  1. Adults due to—- muscle necrosis or trauma
    Children due to—- viral infection
  2. Myoglobin (stores O2, Hb doesnot—-only transports o2 & CO2)
91
Q

1 hemoglobin can bind to ____ oxygen due to?
1 myoglobin can bind to ____ oxygen due to?

______ has much higher affinity of oxygen than other?

A
  1. 4 oxygen due to 4 heme
  2. 1 oxygen due to 1 heme

Myoglobin

92
Q

Hb bind to oxygen at _____ partial pressure and released at _____ pO2?

A
  1. High pO2 (e.g in lungs, binds with O2)
  2. At low pO2 (e.g in tissues, releases O2)
93
Q

About ______ CO2 is carried in blood directly bound to Hb and rest is transported as ____?

A

1.15%
2. Bicarbonate

94
Q

1.CO2 binds to uncharged a-aminoacids of hemoglobin to form_____?

2.What happens to oxygen affinity of Hb as CO2 binds?

A

carbaminohemoglobin

  1. Decreased,
    As CO2 stabilized the taut form of Hb structure
95
Q

The oxyHb can bind ____ moles of CO2/mole of heme
Whereas deoxyHb can bind?

A
  1. O.15
  2. O.40
96
Q

How Hb helps in CO2 transport as bicarbonate?

A

In peripheral tissues

When CO2 enters blood from tissues
|
CO2 + H20 (carbonic anhydrase)
|
H2CO3 —– dissociates
|
HCO3- + H+
|
(Hb4O2 binds to H+ & releases 02 to peripheral tissues)

In lungs

Hb2H+ binds to 02 & releases 2H+
|
H+. + HCO3-
|
H2CO3 (carbonic anhydrase)
|
H20 + CO2 (to lungs–exhaled)

97
Q

1.Hemoglobin acts as ____ & quickly binds with protons released during dissoviation of H2CO3

  1. For evey 2 protons bound to Hb ______ O2 molecules are released to tissues?
A
  1. Buffer
  2. 4 O2
98
Q

What is Bohr effect?

A

Bohr’s effect refers to the phenomenon where an
increase in CO2 levels or a
decrease in pH (acidic conditions)
causes a;
decrease in the affinity of hemoglobin for oxygen.

This allows for easier release of oxygen to the tissues.
(As in the actively metabolizing cells;
CO2 increases
pH decreases)

99
Q

Boht effect causes shift in the oxygen dissociation curve to the?

A

Right ( less saturation of Hb woth 02)

100
Q

What is thalassemia?
2. What are the 4 main causes?

A

Thalassemia is a genetic blood disorder characterized by abnormal production of hemoglobin, leading to anemia.

-heredity hemolytic disorder

  • impairment/imbalance in the synthesis of globin chains of Hb (a- or B- chain)
  • but no abnormality in amino acid of individual chain
  1. Causes;
  2. Gene deletion/substitution
  3. Underproduction or instability of mRNA
  4. Defect in chain synthesis initiation
  5. Premature chain termination
101
Q

What are the major types of thalassemias? Name their subtypes?

A

Two major categories of thalssemia;

1.a-Thalassemias
-absence of ,a-globin chain of Hb
- 4 copies of a-globin gene: **2 **on each of chromosome 16

4 Subtypes; depends on number of missing a-globin genes

•Silent carrier
Loss of 1/4 a-globin gene

•a-Thalassemia trait
-Loss of 2/4
-minor anemia

•Hemoglobin-H disease
-Loss of 3/4 genes
-moderate anemia

•Hydrops fetalis
- loss of all 4/4 genes
- Most severe
- fetus survives untill birth then dies

B_______________________________

2.B-Thalassemias
-absence of ,B-globin chain of Hb (present on
Chromosome 11)
- normal production of ,a-globin chain of Hb—- preciptate—-death of erythrocytes

2 subtypes:

1.B-Thalassemia minor

-heterozygous state (defect in 1 of the 2 B-globin gene pair
- B-thalassemia trait
- asymptomatic

2.B-Thalassemia major

-homoozygous state (defect in both B-globin genes
- infant—-healthy at birth—- become severly anemic—-die within 1-2 years

102
Q

There are _____ copies of a-globulin gene, _____ on each of one of the chromosome ____?

A
  1. 4 copies
  2. 2
  3. Chromosome 16
103
Q

1.________ thalassemia is also called B-thalasemia trait?

2.a-globin gene is present on chromosome _____
And b-globin gene on chromosome______?

A

1.B- thalassemia minor

2.
a-globin on 16
B-globin on 11

104
Q

Name hemoglobin derivatives in normal blood?

These derivatives can be detected by?

A
  1. OxyHb
  2. DeoxyHb
  3. Methemoglobin (MetHb)
  4. Carboxyhemoglobin

Absorption spectra—- Have characteristic colour

105
Q

For hemoglobin to carry oxygen, the iron should remain at which state?

In which state it doesn’t carry oxygen?

A

1.Ferrous (Fe+2)

  1. When oxidized to methemoglobin (Fe+3)
106
Q

1.oxidation of Hb to metHb may be caused by?

2.MetHb—– to Hb in done by?

3.Does molecular oxygen oxidize Hb?

A
  1. H2O2, free radicals & drugs
  2. Methemoglobin reductase found in erythrocytes.

3.No, it just loosely binds with Hb to form oxyhemoglobin

107
Q

1.What is carboxyhemoglobin (CoHb)?

  1. Clinical manifestation shown when COHb conc increases?
A
  1. When carbon monoxide (CO) a toxic substance binds to Hb (affinity= 200 times > than 02)
  2. 20%
    Breathlessness
    Headache
    Vomiting
108
Q

1.Abnormal hemoglobins are the result of?

  1. _______ mutants Hb are known?
  2. ______ of them are due to alteration in a single amino acid of globin?
A

1.Mutations in the genes than codes for a & B chain of globin.

  1. 400

3.95%

109
Q

1.What is hemoglobinopathies?

2.Examples of both types?

A
  1. Term for synthesis of :
    abnormal Hb
    (E.g
    Sickle-cell anemia (HbS)
    Hemoglobin C disease (HbC))

Or synthesis of;
Insufficient quantities of normal Hb
(E.g;
Thalassemias

110
Q

Most common form of abnormal hemoglobin? And 2nd most common?

It is common in which population?

A

Sickle cell anemia (HbS)
After it; HbE

In black population

111
Q

In sickle cell anemia, which chains are normal & abnormal?

Why?

What is the change in nucleotide??
And the altered codon formed?

A
  1. 2 normal a- chains
    2 abnormal(mutant) B-chains
  2. Due to difference in a single amino acid;
    Glutamate replaced by valine
    At position 6 of B-chain
  3. Missense mutation
    (A missense mutation is a type of genetic mutation where asingle nucleotide change results in a different amino acid being incorporated into a protein.)
    •Thymine——Adenine
    • altered codon;
    GUG instead of GAG
112
Q

What are homozygous and heterozygous HbS?

Which is called the sickle cell trait?

A

homozygous
Caused by mutation in both genes that code for B-chain

heterozygous
Caused by mutation in a single gene that code for B-chain
- erythrocyte contain both HbS and HbA
- more common in black

  1. Heterozygous HbS
113
Q

Sicking is due to polymerization of________? And can be prevented when?

  1. Why?
  2. Why deoxyHbA can’t form aggregation?
A
  1. DeoxyHbS
    Prevented when HbS is maintained in oxygenated form
  2. Because of sticky patches and receptors in deoxyHbS
    (Forms long aggregates with other deoxyHbS)
    (OxyHbS only has sticky patches— no receptors—- so forms no aggregation)
  3. Only receptors, No sticky patches
    (Sticky patches are present only in HbS)
    (OxyHbA—- neither sticky patch nor receptor)
114
Q

Glutamate is a ______ amino acid and is replaced by ______ valine so decreases the solubility of HbS in _______ form and solubility of HbS is unaffected in ______ form?

A
  1. Polar
  2. Non-polar
  3. Deoxygenated
  4. Oxygenated
115
Q

Name the abnormalities associates with HbS?

A
  1. Life-long hemolytic anemia (sickled RBC breakdown)
  2. Tissue damage and pain
    (Sickled RBC block capillaries—-reduce blood supply)
  3. Increased susceptibility to infection
  4. Premature death
    (Homozygous—- die before reaching 20 years)
116
Q

1.Sickle cell trait (heterozygous state with 40% HbS) provides resistance to?

  1. How?
A

1.Malaria

  1. • Malarial parasite spends a part of its life cycle in erythrocytes——sickled cell have shorter life span than normal (lysis) —- interrupts parasytic cycle
    • malarial parasite—- pH of cell more acidic (0.4)—– low pH increases sickling to 40% (normally 2%)
    • low K+ conc. In sickled cells—-unfavourable for parasite
117
Q
  1. Malaria is a parasitic disease caused by?
A

1.plasmodium falciparum

118
Q

Diagnosis of sickle cell anemia is done by which methods?

A

1. Sickling test
(Blood smear under microscope—-prepared by reducing agent sodium metabisulfite)

2. Electrophoresis
(In alkaline medium (pH=8.6)
HbS moves slower towards anode (+) than HbA
(Bcz Less -ve due to absent glutamate))

3. Test to detect genes of HbS

119
Q

1.Sickling of erythrocytes is inhibited by? How?

  1. Side effects?
  2. Other treatment & side effect?
A

1.Sodium cyanate
(Cyanate—-increases the affinity of 02 to HbS—- lowers deoxyHbS)

  1. Peripheral nerve damage
  2. • Repeated blood transfusion
    Side effect;
    Iron overload—cirrhosis of liver
    • replacement of Hbs with other forms such as HbF
120
Q

Substitution of glutmate by ________ aminoacids in ______ position of B-chain in ;
HbS
HbC (Cooley’s hemoglobinemia)
HbD
Hb E

Their movement on electrophoresis?

A

•HbS—- by valine at 6
•HbC —by lysine at 6
•HbD—by glutamine at 121
•HbE—-by lysine at 26

Movement——————————-

HbS—- slower than HbA
HbC—- slower than HbA &HbS
HbD—- along with HbS

121
Q
  1. The most abundant organic phosphate in erythrocyte?
  2. Formed in ? from?
A
  1. 2,3 Bisphosphoglycerate (2,3 BPG)
  2. Formed in erythrocyte from;
    An intermediate of glycolysis;
    1,3 Bisphosphoglycerate (1,3 BPG)
122
Q

2,3 BPG binds to _______ and _____ the O2 affinity to Hb? Importance?

  1. 2,3 BPG shifts the oxygen dissociation curve to?
A

1.DeoxyHb
2.Decreases
Importance:
Releases 02 to tissues
3. Right (less saturation of Hb with O2)

123
Q

1 molecule of 2,3 BPG binds to 1 molecule (tetramer) of deoxyHb at?

  1. Where are the +ve charges in deoxyHb?
  2. What bond is formed between 2,3 BPG & deoxyHb?
A
  1. The central cavity of 4 subunits
  2. Central pocket has +vely charged two B-chains
    (E.g histidine, lysine +ve amino acids)
  3. Ionic bond (salt bridges)
    Between +ve amino acids of B-chain & -ve phosphate of 2,3 BPG
124
Q

2,3 BPG levels are related to the tissue demand of 02 supply, why? so jts levels are;
Elevated in?
Decreased in?

A

Bcz binding of 2,3 BPG releases 02 to tissues

  1. Elevated in;
    •Hypoxia
    •Anemia
  2. Decreased in;
    •Blood transfusion:
    Of blood that was stored in citrate dextrose medium
    (So dec conc. Of 2,3 BPG—– so fails to supply O2 to tissues immediately )

•Fetal Hemoglobin
-weak binding of Hb to 2,3 BPG
- HbF has high affinity for 02
- for transfer of O2 from maternal blood to fetus

125
Q

Addition of what to stpred blood prevents the decrease of 2,3 BPG levels?
How?

A

Inosine
(Inosine is a nucleoside that is formed when a hypoxanthine base is attached to a ribose sugar)

-Ribose of inosine gets phosphorylated and enters hexose monophosphate pathway——— finally gets converted to 2,3 BPG

126
Q

What is acute mountain sickness?

Prevention/treatment?

A

When you rapidly ascend to high altitudes (3000-4000 meters), the lower oxygen levels (hypoxia) and changes in atmospheric pressure can cause acute mountain sickness.

  • by administering Acetazolamide

Acetazolamide works by inhibiting carbonic anhydrase, which reduces the production of bicarbonate.
This leads to increased ventilation and improved oxygenation.

127
Q

What are allosteric effectors?

A

Allosteric effectors are molecules that can bind to a protein and modulate its activity.

allosteric effectors can bind to hemoglobin and modulate its affinity for oxygen.

  1. 2,3 BPG
  2. CO2
  3. H+
  4. Cl-

Facilitate release of 02 from oxy Hb

Biochemistry (10 decks)

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