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Y1B3 (CVS & IBL) 📘 > Biochemistry 🧪 > Flashcards

Biochemistry 🧪 Flashcards

1
Q

What are porphyrins?

A

are cyclic compounds synthesized in the human body

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2
Q

What do porphyrins form?

A

metalloporphyrins (Haem). “After conjugation with metals”

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3
Q

What is the result of the conjugation of heme with proteins?

A

Haemoproteins:

1) Haemoglobin of RBCs.
2) Myoglobin of muscle.
3) Cytochromes: Respiratory enzymes in the electron transport chain.

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4
Q

What contains FE-porphyrins as prosthetic “synthetic” groups?

A

Haemoproteins:

1) Haemoglobin of RBCs.
2) Myoglobin of muscle.
3) Cytochromes: Respiratory enzymes in the electron transport chain.

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5
Q

What is porphyrins chemistry?

A
  • They are complex structures consisting of 4 pyrrole rings, united by “methylene” bridges.
  • The nitrogen of 4 pyrrole rings can form complex with metallic ions such as Fe++
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6
Q

What are the sites of synthesis of heme?

A
  • Porphyrins are synthesized partly in the mitochondria and partly in the cytosol of most body tissues except mature red blood cells (due to lack of mitochondria) mainly in:

 Bone marrow (80%). “Site of formation of RBCs”

 Liver (15%). “Many mitochondria, hemoproteins that detoxify”

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7
Q

What are the steps of the synthesis of heme?

A

Step 1: Synthesis of δ-Amino Levulinic Acid (δ-ALA) (Intramitochondrial)

Step 2: Formation of Porphobilinogen (PBG) (Cytosolic)

Step 3 & 4: Formation of Uroporphyrinogen (Cytosolic)

Step 5: Formation of Coproporphyrinogen: (Cytosolic)

Step 6-8: Formation of haem: (Intramitochondrial)

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8
Q

What are the events that happened in step one of heme synthesis?

A

Glycine and succinyl CoA condense to form ALA in a reaction catalyzed by ALA synthase.

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9
Q

What is the rate-controlling step in hepatic porphyrin biosynthesis?

A

Step 1

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10
Q

What are the events that happen in step two of heme synthesis?

A

Two molecules of ALA condense to form porphobilinogen (PBG) “first payroll ring compound” by ALA dehydratase. “Removal of h2o”

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11
Q

What is ala dehydratase sensitive to?

A

ALA dehydratase is extremely sensitive to inhibition by heavy metal ions.

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12
Q

What does lead poisoning lead to?

A

leads to the accumulation of ALA and anemia.

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13
Q

What are the events that happen in step three of haem synthesis?

A

Four molecules of porphobilinogens (PBG) are condensed together by PBG deaminase, producing the linear tetrapyrrole, hydroxymethylbilane.

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14
Q

What are the events that happen in step four of haem synthesis?

A
  • Ring closure and isomerization of hydroxymethylbilane produce uroporphyrinogen III.
  • This reaction is catalyzed by the enzyme uroporphyrinogen III synthase.
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15
Q

What are the events that happen in step five of heme synthesis?

A

Uroporphyrinogens undergo decarboxylation of their acetate groups, catalyzed by the enzyme uroporphyrinogen decarboxylase, generating coproporphyrinogens.

“Uro—->copro”

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16
Q

What are the events that take place in steps from No. 6 to number 8 in heme synthesis?

A

 The 2 side chains of coproporphyrinogen are decarboxylated generating protoporphyrinogen IX. “Copro—>proto”

 Proto-porphyrinogen IX is oxidized to proto-porphyrin IX.

 The introduction of iron (as Fe+2) into proto-porphyrin IX occurs spontaneously, but the rate is enhanced by the ferrochelatase enzyme, which is inhibited by lead.

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17
Q

How is heme regulation Done?

A

The key regulatory enzyme is δ-ALA synthase (in mitochondria).

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18
Q

What are the regulatory influences and effects of inhibitors in heme synthesis

A

1) Effect of O2: haem synthesis is stimulated by low O2 tension (e.g. living at high altitudes). “Negative feedback”
2) Steroids: Stimulate δ-ALA synthetase.
3) Iron: Stimulate δ-ALA synthetase.
4) Lead: It is known to produce profound abnormalities in porphyrin metabolism. It inhibits δ-ALA synthetase, δ-ALA dehydratase “most sensitive” and haem synthetase.

“Stimulate—>ISO”

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19
Q

What is the definition of Porphyrias?

A

❖ Porphyrias are the metabolic disorders of heme synthesis, characterized by accumulation and increased excretion of porphyrins or their precursors.

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20
Q

What causes porphyrias?

A

❖ Porphyrias may be due to deficiency of one or more of heme biosynthesis enzymes → ↓ heme production → ↑ porphyrins.

❖ E.g.: uroporphyrin synthetase - uroporphyrin decarboxylase – coproporphyrin oxidase.

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21
Q

what are the types of porphyrias?

A

❖ Porphyrias are either congenital or acquired.

❖ Acquired porphyria may be due to intake of:

1) Sulfonamides (antibacterial).
2) Sulfonylureas (antidiabetic).
3) Barbiturates (anticonvulsant).
4) Antifungals e.g. griseofulvin.

❖ The most common acquired form of porphyria is due to lead poisoning. “Non-drug induced”

“Sulf sulf barb fungal”

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22
Q

What are the manifestations of porphyrias?

A

1) Abdominal pain.
2) Neuropsychiatric symptoms.
3) Photosensitivity: There are skin itches and burns (pruritis) when exposed to visible light
4) Porphyrinuria: Porphyrins are excreted in urine → dark urine.

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23
Q

What causes photosensitivity in porphyrias?

A

Due to the presence of increased amounts of uro-, copro-, protoporphyrins in tissues with strong absorption of light at 400 nm wavelength, associated with the release of energy and free radicals → tissue damage.

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24
Q

What is the definition of hemoglobin?

A

Tetrameric protein molecule found exclusively in the cytoplasm of Red blood cells (RBCS).

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25
Q

What is the main function of hemoglobin?

A

Is to transport oxygen from lungs to the tissues & carbon dioxide and H protons from tissues to lung “To be exerted, so it maintains acid base balance”

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26
Q

What is the chemical nature of hemoglobin?

A

 Conjugated protein: formed of protein part: globin & non- protein part: heme group “prosthetic group”

 Hemoprotein: contains heme as a tightly bound prosthetic group

 Chromoprotein: has a red colour in vertebrates as it contains a pigmented prosthetic heme group (or cofactor), which is the iron containing molecule that makes oxygenated blood appear red

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27
Q

What is the chemical structure of hemoglobin?

A
  • Hb is a tetramer consisting of 2 parts:
     Heme: 4 heme molecules
     Globin: 4 polypeptide chains
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28
Q

What is the chemical structure of heme?

A

 Heme is a complex of tetrapyrrol ring called protoporphyrin IX & ferrous iron (Fe2+)

 The iron is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring.

 The Heme Fe2+ can form two additional bonds, one on each side of the porphyrin ring:
✓ One of these positions is coordinated to the side chain of a histidine amino acid of the globin molecule, Whereas the other position is available to bind oxygen

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29
Q

What is globin?

A

Globin is a protein rich in histidine amino acid, with a quaternary structure (formed of 4 polypeptide chains)

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30
Q

What does each chain of globin contain?

A

Each chain (subunit) has stretches of α-helical structure and a hydrophobic heme- binding pocket.

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31
Q

What are the types of globin chains?

A

There are four types of globin chains: α, β, γ and δ (According to sequence of amino acids in the primary structure of each chain)

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32
Q

What is the type of bonds between the chains of hemoglobin and what is the number of amino acids in each chain?

A

non-covalent bonds:
✓ α -chains contain 141 amino acids.
✓ β -chains contain 146 amino acids.

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33
Q

What are the types of hemoglobin classified according to?

A

the primary structure of the globin polypeptide chains.

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34
Q

What are the types of hemoglobin?

A

Hb A or HbA1 (Adult Hb)

Hemoglobin A2 (HbA2)

Fetal hemoglobin (Hb F)

Hemoglobin A1c (HBA1c) “doesn’t affect the function”

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35
Q

What does HBA1 represent and what is composed of?

A

 Is the major form of normal Hb in adults represents about 90-95% of total Hb. “ 6 months after birth”

 It is composed of 2 α and 2 β chains.

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36
Q

What does HBA2 represent and what is it composed of?

A

 Minor adult Hb, comprised 2-3% of normal adult Hb.

 Composed of 2 α and 2 δ chains

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37
Q

What does HBF represent what is it composed of?

A

 Is the main Hb during fetal life and in newborns then disappear gradually where it is replaced by Hb A shortly after birth.

 It is composed of 2α and 2 γ chains.

38
Q

What does HBA1C represent and what is it composed of?

A
  • Normally, it is present in conc. of 3 - 5 % of total Hb. However, in patients with D.M. it may be increased to as much as 6 -15 % of total Hb.
  • Formed spontaneously by nonenzymatic reaction of hemoglobin A with Glucose (HBA1c has a glucose residues attached to β-globin chains in RBCs hemoglobin by non-enzymatic reaction).
39
Q

What does a greater affinity to O2 HBA or HBF?

A
  • Hb F has greater affinity for O2 than HbA so ensure O2 transfer from maternal circulation to fetus RBCs through placenta. “May cause problems” “less than 1% in adults”
40
Q

What does the extent of glycosylation depend on in HBA1C?

A

the plasma conc. of glucose.

41
Q

What is HBA1c used for?

A

HbA1c could be used as a monitor for the control of the blood glucose level during the last 2 months for diabetic patients. “ HB lifetime is two months “

42
Q

What are hemoglobinopathies?

A
  • They are members of a family of genetic disorders caused by genetic mutations in the genes producing globin protein of hemoglobin
43
Q

What are hemoglobinopathies characterized by?

A
  • Production of a structurally abnormal hemoglobin molecule (Qualitative hemoglobinopathies): eg: HbS & HbM.
  • Synthesis of insufficient quantities of normal hemoglobin (Quantitative hemoglobinopathies): eg: Thalasaemias.
44
Q

What is sickle cell anemia and what causes it (HB S disease)?

A
  • Genetic disorder caused by mutation in 6th codon of the β-globin “In globin of hemoglobin” gene where glutamic acid (GAG) is replaced by valine (GTG).
45
Q

What is a pathogenesis of sickle cell anemia?

A
  • Valine residues aggregate together by hydrophobic interactions leading to precipitation of abnormal Hb within RBCs (Hb S).
46
Q

What is the result of sickle cell anemia?

A
  • RBCs which are sickle-shaped lead to fragility of their walls and high rate of hemolysis
  • Such sickled cells frequently block flow of blood in narrow capillaries and block blood supply to tissue (tissue anoxia) causing pain and cell death.
47
Q

What is the definition of thalassemias?

A

A group of genetic diseases in which synthesis of either α- or β- globin chain is defective.

48
Q

What are the causes of thalassemias?

A

This due to defect or absence of one or more of genes responsible for synthesis of α or β globin chains of Hb molecule leading to malformed RBC.

“Not just a mutation in the 6th codon of the gene responsible for the synthesis of beta globin chain”

49
Q

What are the types of thalassemias?

A
  • α-thalassemia: in which synthesis of α globin chain is defective or absent
  • β -thalassemia: When synthesis of β globin chain is decreased or absent.“May cause death”
50
Q

What are the sites of hemoglobin degradation and when does it happen?

A
  • In reticuloendothelial system: liver, spleen &bone marrow
  • After approximately 120 days in the circulation: RBCs taken up by RES especially spleen and liver where HB become degraded.
51
Q

What are the steps of hemoglobin degradation?

A

1) Formation of Bilirubin
2) Uptake of bilirubin by liver
3) Conjugation of bilirubin (Formation of bilirubin diglucuronide)
4) Excretion of bilirubin into bile

52
Q

What happens when RBCs end their lifespan?

A
  • The globin is degraded to amino acids (which are reutilized in the body)
  • Heme releases iron (which is returned to the body’s iron stores), and the tetrapyrrole component is converted to bilirubin, which is mainly excreted into the bowel via the bile.
53
Q

Step one: formation of bilirubin

A
  • Heme under the effect of heme oxygenase “in macrophages” in presence of NADPH+H become converted to Biliverdin, and iron become oxidized into ferric and released.
  • Biliverdin is then reduced via biliverdin reductase enzyme and become converted into bilirubin.

“Heme to bilivirdin”
“Ferrous to ferric”

54
Q

Step two: uptake of bilirubin by liver

A
  • Bilirubin is hydrophobic, so, it is transported in blood by albumin [ (unconjugated) (Indirect bilirubin (Hemobilirubin)]
  • Then bilirubin uptake by the hepatocytes takes place where it dissociated from albumin.
55
Q

Step three: conjugation of bilirubin (formation of bilirubin diglucuronide)

A
  • Conjugation of bilirubin to 2 molecules of glucuronic acids occurs in hepatocytes to increase its solubility.

✓ This catalyzed by bilirubin UDP glucuronyltransferase enzyme.

  • The product is bilirubin diglucuronide (conjugated bilirubin) (direct bilirubin) (cholebilirubin).
56
Q

What is other name for unconjugated bilirubin what is the other name for conjugated bilirubin?

A

Unconjugated bilirubin is referred to as indirect bilirubin, while conjugated bilirubin is referred to as direct bilirubin

57
Q

Step 4: excretion of bilirubin in to bile

A
  • Conjugated Bilirubin passes with the bile to the large intestine where glucuronic acid is removed leaving bilirubin. “No need anymore”
  • It is converted into stercobilinogen and urobilinogen by intestinal bacteria.

✓ Then stercobilinogen is then oxidized to stercobilin which give feces it characteristic brown color

  • Some urobilinogen is reabsorbed into blood via portal circulation to the liver and then re-excreted into bile (enterohepatic urobilinogen cycle).
  • The remaining urobilinogen is transported via blood to the kidney

✓ Converted to yellow urobilin and excreted through urine.

✓ This gives urine its characteristic color

58
Q

What does the increase in the level of blood bilirubin (hyperbilirubinemia) indicate?

A

Increase in the level of the blood bilirubin (hyperbilirubinemia) is a case of Jaundice (yellow discoloration of skin, conjunctiva and mucous membrane)

59
Q

What is the composition of plasma?

A

Water: 90 %

Inorganic substances: 0.9%

  • Cations: Na+ / K+
  • Anions: Cl / HCO3 / PO4 / SO4

Organic substances: 9.1 %

  • Plasma proteins: (6-8 gm%) (6-8GM/DL)
  • Lipids
  • Others
60
Q

What is the level of total proteins in plasma?

A

about 7-7.5 g/dl. “dl=100ml”

61
Q

What is the composition of plasma proteins?

A

Plasma proteins include not only simple proteins but also conjugated proteins as glycoproteins and lipoproteins.

62
Q

What are the types of plasma proteins?

A

Plasma proteins can be classified into 3 main groups: albumin, globulins (α1, α2, β and y ) and fibrinogen.

63
Q

Where are plasma proteins synthesized?

A

Most plasma proteins are synthesized in the liver. However, Y globulins “antibodies” are synthesized by plasma cells and B cells of lymphoid tissues.

64
Q

What is the definition of albumin and what is its levels in blood?

A
  • Is the major human plasma protein (60% of total plasma protein).
  • 3.5-5.5 g/dl
65
Q

What are the functions of albumin?

A

“Osmotic pressure - carrier - treatment of hemorrhage and burns”

  • Responsible for 70 to 80% of osmotic pressure of human plasma.
  • Helps in transport of several substances e.g., FFA, unconjugated bilirubin, Ca++ and steroid hormones”also carried by globulins”.
  • Certain drugs also bind to albumin, e.g., sulphonamides, aspirin, penicillin and are transported to target tissue.
  • Preparations of human albumin have been widely used in treatment of hemorrhagic shock and burns.
66
Q

What are alpha-1 globulins? “Markers”

A

α1-acid glycoprotein (orosomucoid)

α1-antitrypsin (α- AT)

67
Q

What is the function of alpha 1 - acid Glycoproteins (Orosomucoid)?

A

A reliable indicator of acute inflammation. “Its increase”

68
Q

What is the function of alpha 1 - antitrypsin?

A

It is the principal protease inhibitor (Pi) of human plasma: It inhibits trypsin, elastase and other proteases by forming complexes with them.

  • It is deficient in emphysema.
69
Q

What are alpha-2 globulins? “Carriers”

A

Haptoglobin

70
Q

What is the function of haptoglobulin?

A
  • Bind free Hb and minimizes urinary loss of Hb.
  • After binding, Hp-Hb complex circulates in the blood,
    which cannot pass through glomerular filter and ultimately the complex is destroyed by RE cells.
71
Q

What are beta globulins?

A

β- Lipoproteins (LDL) “bad”

Transferrin “carrier”

C-reactive Protein

72
Q

What is the function of transferrin?

A

transport of Fe between intestine and site of synthesis of Hb and other Fe containing proteins.

73
Q

What is the function of C-reactive proteins?

A
  • It precipitates with group C polysaccharide of pneumococci, in the presence of Ca, hence the name.
  • It can bind to T-lymphocytes and can activate complement.
  • Used as a marker of tissue injury & inflammation.
74
Q

What are gamma globulins?

A

These are immunoglobulins having antibody activity.

75
Q

What is fibrinogen?

A
  • also called clotting factor I,

- as it takes part in coagulation of blood.

76
Q

What are the functions of plasma proteins?

A 
Nutritive
Fluid exchange (colloid osmotic pressure)
Buffering action
Binding and transport function
Blood coagulation and fibrinolysis
Immunological function
Enzymes
Carriage of CO2
77
Q

What is the nutritive function of plasma proteins?

A

contribute amino acids for tissue protein synthesis.

78
Q

How do plasma proteins affect fluid exchange?

A

Regulation of blood volume and tissue fluid formation: plasma proteins exert osmotic pressure across the capillary wall which tend to pull water into the blood.

79
Q

What is the buffering action of plasma proteins?

A

The serum proteins, like other proteins, are amphoteric, they have free acidic (R-COOH) and basic (R-NH2) end so can act as weak acid or base and thus can combine with acids or bases.

80
Q

What do plasma proteins transport?

A

✓ Albumin → binds various ligands (thyroxine, steroids, a a, vitamins and FA).

✓ Haptoglobin→binds extra corpuscular HB

✓ Apolipoproteins → Lipoproteins

✓ Thyroid-binding globulin → binds T3 & T4
✓ Transferrin → transports iron.

✓ Ceruplasmin → copper

✓ Steroid hormone – binding globulin → steroid hormone

✓ Transcobalamin→vit B12 “cobolamin”

81
Q

What is the Immunological function of plasma proteins?

A

Y-globulins protect the body against microbial infections.

82
Q

What is the enzymatic function of plasma proteins?

A

Enzymes are proteins.

83
Q

How do plasma proteins Carry co2?

A

Co2 combines with the amino group of the plasma proteins and is carried as carbamino compounds.

84
Q

What is the most common method of analyzing plasma proteins?

A

Electrophoresis

85
Q

Mention a method used to analyze plasma proteins.

A

Serum protein electrophoresis: By cellulose acetate electrophoresis, the serum can be separated into a number of fractions (albumin, α1, α2, β and γ globulins).

86
Q

What does deficiency of albumin in Cellulose acetate electrophoresis indicates?

A

Nephrotic syndrome or cirrhosis of liver

87
Q

What are acute phase proteins (or reactants)?

A

Levels of certain proteins in plasma increase during acute inflammatory states or secondary to certain types of tissue damage. These proteins are called Acute phase proteins or reactants.

88
Q

What are examples of acute phase proteins?

A

C-reactive protein (CRP)
Haptoglobin (Hp)
α1 antitrypsin
α1 acid glycoprotein (orosomucoid) and fibrinogen

“All studied except LDL and transferrin”

89
Q

What are the causes of hypoproteinemia?

A

 Hemodilution: overload from IV infusion.
 Hypoalbuminemia:
 Hypogammaglobulinemia

90
Q

What are the causes of hypoalbuminemia?

A

Loss from the body:

  • Renal: Loss of albumin in urine in nephrotic syndrome. - - GI Tract: Protein losing enteropathy.
  • Skin: Burns and other exudative skin lesions.

Decreased synthesis of albumin:

  • Severe liver diseases: Chronic hepatitis, cirrhosis liver.
  • Genetic deficiency: Analbuminaemic “rare, the gene responsible”

Miscellaneous: Pregnancy, chronic illness

91
Q

What are the causes of hypogammaglobinemia?

A

✓ Protein loss: Same as above.

✓ Decreased synthesis:
o Primary: Genetic deficiency “very rare”
o Secondary” suppressing the immunity” : Certain toxins/and drugs: uremia, cytotoxic therapy, corticosteroid therapy, AIDS

✓ Miscellaneous: Pregnancy.

92
Q

What are the effects of hypoproteinemia?

A
  • Swelling of face and other parts of the body. “Due to loss of oncotic pressure”
  • Edema L.L. “Due to loss of oncotic pressure”
  • Loss of muscle mass “Deficiency of proteins”
  • Infections “Decreased immunity”
  • Fatigue “Decreased immunity”
  • Dry brittle hair
  • Lack of growth in children.

Y1B3 (CVS & IBL) 📘 (10 decks)

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