🔥 Flashcards
(162 cards)
1
Q
What is the composition of Haemoglobin?
A
Haemoglobin = Haem + globin (Protein)
Haem consists of Iron + Porphyrins.
2
Q
What are Porphyrins?
A
Cyclic compounds derived from Porphin nucleus made of 4 pyrrole rings linked by 4 methenyl bridges
In nature, side chains are substituted for H atoms.
3
Q
What is the difference between Type I and Type III isomers of Porphyrins?
A
Type I: Substituted groups are symmetrically arranged
Type III: Substituted groups are arranged in reverse order
Biologically important Porphyrins in Haem and Cytochromes are Type III isomer.
4
Q
What is the oxidation state of Iron in Haem?
A
Ferrous state (Fe+2)
Iron is linked to 4 Nitrogen atoms of 4 Pyrrole.
5
Q
What are the coordination bonds in Haem?
A
5th bond linked to N of Imidazole ring of proximal Histidine, 6th bond linked to Oxygen in HbO2
The 6th bond is empty in Deoxy Hb.
6
Q
What is the composition of Globin in Haemoglobin?
A
Composed of 4 polypeptide chains: 2α chains and 2β chains
α chain has 141 amino acids, β chain has 146 amino acids.
7
Q
What are the types of normal Hemoglobin?
A
- Adult Hb (HbA)
- Glycosylated Hb (HbA1C)
- Fetal Hb (HbF)
Each type has specific characteristics and compositions.
8
Q
What is the composition of Adult Hemoglobin (HbA)?
A
HbA (α2β2): Contains 2 Alpha chains and 2 Beta chains
Constitutes 95-97% of total Hb.
9
Q
What is Glycosylated Hemoglobin (HbA1C)?
A
Modified form of Hb with glucose linked to ε-amino group of lysine
Useful for assessing diabetic control; normal value is 5%.
10
Q
What is Fetal Hemoglobin (HbF) composed of?
A
HbF (α2γ2): Consists of 2 Alpha chains and 2 Gamma chains
HbF has a greater affinity for O2.
11
Q
What is Sickle cell disease (HbS)?
A
Mutation where Glutamic acid is replaced by Valine at the 6th position of Beta chain
Leads to formation of sticky patches and sickling of RBCs.
12
Q
What are the effects of sickling of RBCs?
A
- Anemia (sickle cell anemia)
- Thrombus formation
- Damage to tissues and organs
Affects organs like the brain, bone, and spleen.
13
Q
What is Thalassemia?
A
Hereditary hemolytic diseases where synthesis of α or β globin chain is defective
Due to mutation affecting the regulatory gene.
14
Q
What types of Thalassemia exist?
A
- α-Thalassemia
- β-Thalassemia
Each type is characterized by specific defects in globin chain synthesis.
15
Q
What is Met Hemoglobinemia?
A
Condition with oxidized Hb, containing Fe+3 instead of Fe+2
The ability to react as an O2 carrier is lost.
16
Q
What causes Congenital Met Hemoglobinemia?
A
Mutation in globin biosynthesis leading to Hb M
Distal or Proximal Histidine is replaced by Tyrosine.
17
Q
What is the treatment for Met Hemoglobinemia?
A
Blood transfusion for congenital cases; reducing agents are ineffective
NADH-Cytochrome b5 Met Hb reductase system is involved in treatment.
18
Q
What is Met Hb reductase?
A
Flavoprotein Cytochrome b5 reductase.
19
Q
What does the Met Hb reductase system do?
A
Reduces heme Fe +3 back to Fe +2 state.
20
Q
What is the effective treatment for Methemoglobinemia?
A
Injection of reducing agents like Vitamin C, Glucose, or Methylene blue.
21
Q
What causes Acquired Methemoglobinemia?
A
Ingestion of large amounts of drugs like Phenacetin, Sulphonamides, excess Nitrites, or certain oxidizing agents in diet.
22
Q
What are the diagnostic indicators of Methemoglobinemia?
A
- Cyanosis
- Examination of blood color (Brownish)
- Pulse Oximetry to test saturation of Blood Oxygen
- DNA sequencing of Globin chain.
23
Q
Where is Haem synthesized primarily?
A
Bone marrow (85%) for synthesis of Hb and liver for synthesis of Cytochromes.
24
Q
What are the initial and last three enzymatic steps of Haem biosynthesis?
A
Mitochondrial Enzymes.
25
What is the first step in Haem biosynthesis?
Synthesis of δ-Amino Levulinic Acid (δ-ALA).
26
What is the role of ALA Synthase in Haem biosynthesis?
It is the rate-limiting step.
27
What are the types of Porphyrias?
* Congenital Porphyrias
* Acquired (Toxic) Porphyrias.
28
What are the clinical signs of Porphyria due to enzymatic block?
Accumulation of metabolites before the block leading to toxic effects.
29
What is the fate of RBCs after they exit from arterioles?
They are destroyed by macrophages in spleen, liver, and bone marrow.
30
What are the main components of Folic Acid?
* Pteridine Nucleus
* P-Amino Benzoic Acid (PABA)
* Glutamic Acid.
31
What is the primary function of Folic Acid?
Formation of the important coenzyme Tetra hydro Folic Acid (THF).
32
What are the sources of one carbon group for Folic Acid?
* Beta carbon of Serine
* Glycine
* Formate.
33
What deficiency can lead to macrocytic anemia?
Folate deficiency.
34
Name a folic acid antagonist used in cancer treatment.
Methotrexate (Amethopterin).
35
What are the two characteristic components of Cobalamin (Vitamin B12)?
* Corrin ring
* Cobalt atom.
36
What is the role of Cobalt in Cobalamin?
Coordinated to the four inner nitrogen atoms of the Corrin ring.
37
What is the primary structural difference between Phyrin and Porphyrin?
Phyrin has 2 Pyrrole rings (A and D) joined directly rather than through a Methenyl bridge.
38
What atom is coordinated to the four inner Nitrogen atoms of the Corrin Ring in Phyrin?
Cobalt.
39
What is the coordination state of Cobalt in Phyrin?
Six.
40
What is the 5th position attached to in Cobalt coordination?
5,6 dimethyl Benzimidazole Riboside.
41
What can the 6th position of Cobalt in Phyrin be coordinated to? (List all possible options)
* Cyanide (CN) → Cyano Cobalamin
* Hydroxyl (OH) → Hydroxy Cobalamin
* Methyl (CH3) → Methyl Cobalamin
* 5 deoxy Adenosine → 5 deoxy Adenosyl Cobalamin.
42
What are the daily requirements for Vitamin B12?
2 µg/day.
43
Why is Vitamin B12 not present in vegetable foods?
Neither animals nor plants can synthesize it.
44
What is the only natural source of Vitamin B12?
Synthesis by microorganisms in the animal intestine.
45
What are the main sources of Vitamin B12?
* Liver
* Kidney
* Meats
* Milk
* Eggs.
46
How is Vitamin B12 utilized in the body?
It is first removed from protein by acid hydrolysis in the stomach, then combines with the intrinsic factor for absorption.
47
What complex crosses the ileal mucosa for Vitamin B12 absorption?
Cobalamin-Intrinsic factor complex.
48
What happens to intrinsic factor after it crosses the ileal mucosa?
Intrinsic factor is released and the vitamin is transferred to plasma (absorbed).
49
What are the two biochemical reactions in which Vitamin B12 participates?
* Methionine Methyl Cobalamin ↔ Hydroxy Cobalamin → Deoxy Adenosyl Cobalamin
* L-Methyl Malonyl CoA → Succinyl CoA.
50
What is the deficiency of Vitamin B12 associated with?
Pernicious anemia → Macrocytic Megaloblastic anemia.
51
What neurologic disorders are associated with Vitamin B12 deficiency?
Interference with myelin sheath integrity leading to sensory and motor losses.
52
What are the daily requirements for Vitamin K?
70 – 140 mg/day.
53
What are the sources of Vitamin K1?
* Vegetable oils
* Green leafy vegetables (spinach, cabbage, cauliflower, peas).
54
Where is Vitamin K2 synthesized?
By intestinal flora and found in animal tissue.
55
What is the main function of Vitamin K?
Required for the conversion of several blood clotting factors (II, VII, IX, X) to the active state.
56
What is the precursor form of Prothrombin synthesized in the liver?
Pre Prothrombin.
57
What is required for the conversion of Pre Prothrombin to active Prothrombin?
Vitamin K dependent carboxylation of glutamic Acid to γ-carboxy glutamic Acid.
58
What does γ-carboxy glutamic Acid allow Prothrombin to do?
Bind (chelate) calcium.
59
What is the antidote to Dicumarol anticoagulant?
Vitamin K.
60
What are the daily iron requirements for adult males?
10 mg/day.
61
What are the sources of dietary iron?
* Organ meats (liver, heart, kidney)
* Whole wheat
* Spinach
* Molasses.
62
What percentage of dietary iron is absorbed in the duodenum?
10%.
63
What factors help iron absorption? (List all)
* Acidity (low pH helps liberate iron)
* Reducing agents (convert Fe+3 to Fe+2).
* Heme iron is absorbed directly.
64
What inhibits iron absorption? (List all)
* Achlorhydria (no HCl)
* Hypochlorhydria (low HCl)
* Phytates
* Oxalates.
65
What is the main storage organ for iron?
Liver.
66
What is the main storage form of iron?
Ferritin.
67
What is the serum level of plasma iron?
50 – 150 μg/dL.
68
What is the Total Iron Binding Capacity (TIBC)?
300 – 360 μg/dL.
69
What is the characteristic of iron deficiency anemia?
Microcytic Hypochromic anemia.
70
What is iron toxicity characterized by?
Excessive accumulation of iron in tissues leading to conditions like Hemochromatosis.
71
What is the structure of an immunoglobulin molecule?
Y shaped with 4 polypeptide chains: 2 identical Light chains and 2 identical Heavy chains linked by disulphide bonds.
72
What regions do the light and heavy chains of immunoglobulins have?
* Variable regions (V_L & V_H)
* Constant regions (C_L & C_H).
73
What is the function of the variable regions in immunoglobulins?
They form the antigen binding site.
74
What are immunoglobulins classified as?
Proteins secreted from Plasma cells on Antigen stimulation.
75
What do immunoglobulins contain that classifies them as glycoproteins?
Carbohydrate group attached to C_H.
76
What are immunoglobulins?
Proteins secreted from plasma cells on antigen stimulation
## Footnote
Immunoglobulins are also known as antibodies.
77
What is the molecular weight of light and heavy chains in immunoglobulins?
Light Chain: Low (32 Kda), Heavy Chain: High (50-70 Kda)
78
How many classes of immunoglobulins are there?
5 classes: IgA, IgD, IgE, IgG, IgM
79
What is the main function of IgG?
Provides passive immunity, antibacterial, antiviral, antitoxins activity, and activates complement
## Footnote
IgG can traverse blood vessels and pass through the placenta.
80
What type of structure does IgM have?
Pentamer
81
What is the role of IgA?
Provides local immunity at mucous membrane surfaces and found in colostrum and milk
## Footnote
IgA exists as a monomer in serum and a dimer in secretions.
82
What triggers the release of mediators in IgE-mediated reactions?
Antigen binding to IgE bound to mast cells or basophils
83
What is the renal sugar threshold (RST) for glucose?
180 mg/dL
84
Fill in the blank: The degradation of glucose to generate ATP is known as _______.
Glycolysis
85
What are the major pathways of glucose oxidation?
* Glycolysis
* Oxidative decarboxylation of Pyruvate
* Citric Acid Cycle (C.A.C)
86
What is produced anaerobically during glycolysis?
2 Lactate + 2 ATP
87
What is the function of Hexokinase in glycolysis?
Catalyzes the first step of glycolysis; high affinity for glucose
88
True or False: Glycolysis occurs in the mitochondria.
False
## Footnote
Glycolysis occurs in the cytosol of all tissues.
89
What does PFK-1 stand for and its importance?
Phosphofructokinase-1; it is the main regulatory enzyme in glycolysis
90
What does the term 'rate limiting enzyme' refer to in glycolysis?
The enzyme that controls the speed of the glycolytic pathway
91
What happens to glucose when blood glucose levels exceed the renal threshold?
Glucose is excreted in urine, a condition known as glucosuria.
92
What are the products of glycolysis under aerobic conditions?
2 Pyruvate + 8 ATP
93
What is the primary function of glycolysis in red blood cells (RBCs)?
It is the only pathway that provides ATP in RBCs.
94
What is the significance of 2,3 bis-phosphoglycerate in red blood cells?
It binds to oxyhemoglobin and lowers hemoglobin's affinity for O2.
95
List the five classes of immunoglobulins.
* IgG
* IgA
* IgM
* IgD
* IgE
96
What are the two types of light chains in immunoglobulins?
* Kappa (K)
* Lambda (λ)
97
What is the main substrate for glycolysis?
Glucose
98
What is the affinity of PFK-1 for glucose characterized by?
High (low Km)
99
Does glucose-6-phosphate act as an allosteric inhibitor?
No Effect
100
What is the effect of insulin on glycolytic key enzymes?
Inducer
101
What is the effect of glucagon on glycolytic key enzymes?
Repressor
102
What state does AMP indicate in the cell?
Low energy state
103
What does ATP indicate in the cell?
High energy state
104
What is the effect of citrate on PFK-1?
Feedback inhibition
105
What is glucagon's role in hormonal regulation of glycolysis?
Acts as a repressor of glycolytic key enzymes
106
What is the effect of insulin in states of hyperglycemia?
Induces synthesis of glycolytic key enzymes
107
What type of modification activates the pyruvate dehydrogenase complex?
Dephosphorylation
108
What is the function of arsenate in glycolysis?
Uncoupler of oxidation and phosphorylation
109
What is the role of pyruvate in metabolism?
Transformed into Acetyl CoA by pyruvate dehydrogenase complex
110
What are the cofactors required for the pyruvate dehydrogenase complex?
* NAD+ * FAD * Coenzyme A (CoASH) * Lipoic Acid * Thiamin pyrophosphate (TPP)
111
What does each mole of Acetyl CoA produce in the citric acid cycle?
12 ATP
112
What are the two phases of the Hexose Monophosphate Pathway?
* Oxidative phase * Non-oxidative phase
113
Where does the Hexose Monophosphate Pathway occur?
Cytosol of many cells
114
What is produced in the oxidative phase of the HMP pathway?
Ribulose 5-P + 2 NADPH + H+
115
What is the importance of the HMP pathway?
* Produces Ribose 5-P * Generator of NADPH + H+ for biosynthesis
116
What does NADPH + H+ contribute to in the body?
Reductive biosynthesis
117
What is the role of the citric acid cycle in metabolism?
Final common metabolic pathway for oxidation of carbohydrates, fats, and proteins
118
Which enzyme complex is inhibited by arsenite and mercury?
Pyruvate dehydrogenase complex
119
What is the total ATP produced from the complete oxidation of one glucose molecule?
38 ATP
120
What is the role of the malate-aspartate shuttle?
Enters mitochondria as NADH + H+, producing 3 ATP
121
What is the significance of citrate in the synthesis of fatty acids and cholesterol?
Transported to cytosol and converted to Acetyl CoA
122
What does the term 'amphibolic pathway' refer to?
Pathway involved in both catabolic and anabolic processes
123
Fill in the blank: The pyruvate dehydrogenase complex requires _______ as a cofactor.
Lipoic Acid
124
True or False: High NADH/NAD+ ratios activate the citric acid cycle.
False
125
What is the primary function of the citric acid cycle?
Energy production through oxidation of Acetyl CoA
126
What is the consequence of arsenate's action in glycolysis?
Interferes with ATP formation at the substrate level
127
What are the consequences of oxidative damage in RBCs due to H2O2?
Oxidative damage leads to the oxidation of Fe+2 in hemoglobin to Fe+3 MetHb, non-functioning lipids, increased cell membrane fragility, and hemolysis.
## Footnote
This process can lead to conditions such as Favism.
128
What role does the HMP pathway play in protecting RBCs from oxidative damage?
The HMP pathway provides NADPH+H+, which is essential for producing reduced glutathione (GSH) to remove H2O2.
## Footnote
GSH is crucial for detoxifying reactive oxygen species.
129
What happens when there is a deficiency of G-6-P dehydrogenase?
Deficiency leads to no NADPH+H+, no GSH, failure to break down H2O2, resulting in fragile RBCs and hemolysis.
## Footnote
This condition is associated with Favism.
130
What is the rate-limiting enzyme in the HMP pathway?
G-6-P dehydrogenase.
## Footnote
It is regulated by inhibition, stimulation, and feedback mechanisms.
131
What is the significance of the Uronic Acid pathway?
It provides an alternative route for glucose oxidation without ATP generation, primarily forming UDP glucuronic acid for detoxification.
## Footnote
This pathway occurs mainly in the liver cytoplasm.
132
What is UDP glucuronic acid used for?
Conjugation to less polar compounds, synthesis of glycosaminoglycans (GAGS), and serving as a precursor of L-ascorbic acid in plants and animals.
## Footnote
Humans do not synthesize L-ascorbic acid from UDP glucuronic acid.
133
What is gluconeogenesis?
The synthesis of glucose and/or glycogen from non-carbohydrate precursors such as lactate, glucogenic amino acids, glycerol, and propionate.
## Footnote
It is crucial during fasting or low carbohydrate diets.
134
Where does gluconeogenesis primarily occur?
90% in the liver and 10% in the kidney cortex.
## Footnote
It involves both cytoplasmic and mitochondrial processes.
135
What are the key enzymes in gluconeogenesis?
Key enzymes include:
* Pyruvate carboxylase
* Phosphoenolpyruvate carboxykinase (PEPCK)
* Fructose 1,6-bisphosphatase
* Glucose-6-phosphatase
## Footnote
These enzymes are critical for reversing glycolysis.
136
What is the role of pyruvate carboxylase in gluconeogenesis?
Converts pyruvate to oxaloacetate, which is then converted to phosphoenolpyruvate (PEP).
## Footnote
It is considered a rate-limiting step in gluconeogenesis.
137
What substrates can be used for gluconeogenesis?
Substrates include:
* Lactate
* Glucogenic amino acids
* Glycerol
* Propionate
## Footnote
All amino acids can contribute to glucose production except leucine.
138
What is the importance of gluconeogenesis during fasting?
Maintains blood glucose levels for essential tissues like the brain, renal medulla, and muscles during starvation or exercise.
## Footnote
It also helps remove lactic acid and regulate acid-base balance.
139
How is gluconeogenesis regulated?
It is reciprocally controlled with glycolysis, influenced by insulin and anti-insulin hormones, and short-term regulators like ATP and citrate.
## Footnote
Insulin represses gluconeogenic enzymes, while glucagon and adrenaline stimulate them.
140
What is glycogenesis?
The intracellular synthesis of glycogen from glucose.
## Footnote
It primarily occurs in the liver and muscle cells.
141
What is the key enzyme in glycogenesis?
Glycogen synthase.
## Footnote
It catalyzes the transfer of glucose units from UDP-glucose to a glycogen primer.
142
What is the role of the branching enzyme in glycogenesis?
Transfers parts of the elongated chain to form new branches in glycogen by α 1,6-glucosidic linkage.
## Footnote
This enzyme is essential for creating branched structures in glycogen.
143
What is the function of liver glycogen?
Acts as a glucose reserve for maintaining blood glucose levels between meals.
## Footnote
Liver glycogen is depleted after 12-18 hours of fasting.
144
What is the significance of muscle glycogen?
Serves as a fuel reserve for ATP generation within the muscle during contraction.
## Footnote
Muscle glycogen is depleted after prolonged exercise.
145
How is glycogenesis regulated by hormones?
Glycogen synthase exists in two forms: active dephosphorylated (a-form) influenced by insulin and inactive phosphorylated (b-form) influenced by glucagon.
## Footnote
Hormonal regulation is crucial for managing energy storage and mobilization.
146
What is the key enzyme in glycogenesis?
Glycogen Synthase
## Footnote
Glycogen Synthase exists in two forms: the active dephosphorylated form (a-form) and the inactive phosphorylated form (b-form).
147
What effect does insulin have on Glycogen Synthase?
Insulin activates Glycogen Synthase by converting it to its dephosphorylated form
## Footnote
This enhances glycogen synthesis.
148
What is the effect of glucagon on Glycogen Synthase?
Glucagon inactivates Glycogen Synthase by phosphorylating it
## Footnote
This occurs in the liver and muscle.
149
What role does G-6-P play in glycogenesis?
G-6-P activates Glycogen Synthase
## Footnote
Accumulation indicates that the cell does not need more oxidation and ATP production.
150
How does free glucose differ in its utilization between liver and muscle cells?
In the liver, G-6-P is converted to free glucose, while in muscle cells, G-6-P is retained
## Footnote
Muscle cells cannot release glucose due to the absence of glucose-6-phosphatase.
151
What is the main site for glycogenolysis?
Cytosol of Liver and Muscles
## Footnote
Glycogenolysis is the intracellular breakdown of glycogen.
152
What is the rate-limiting step in glycogenolysis?
Glycogen Phosphorylase
## Footnote
It acts on α 1,4 glucosidic bonds of glycogen.
153
What is the function of the debranching enzyme in glycogen metabolism?
Removes the last glucose at the branching point by adding H2O, producing free glucose
## Footnote
This enzyme is also known as Amylo 1,6-glucosidase.
154
What hormones activate Glycogen Phosphorylase?
Norepinephrine, Epinephrine, and Glucagon
## Footnote
These hormones activate Glycogen Phosphorylase by phosphorylation.
155
What effect does insulin have on Glycogen Phosphorylase?
Insulin inhibits Glycogen Phosphorylase by dephosphorylating it
## Footnote
This action occurs in both liver and muscle.
156
What is Von Gierke's disease?
A condition due to deficiency of Glucose-6-Phosphatase in the liver
## Footnote
It leads to an inability to release glucose into the bloodstream.
157
What is McArdle syndrome?
A condition due to deficiency of Muscle Phosphorylase
## Footnote
It primarily affects glycogen metabolism in muscles.
158
What is the major dietary source of galactose?
Lactose obtained from milk and milk products
## Footnote
Lactose is digested by the enzyme Lactase.
159
What is galactosemia?
An inherited disease due to deficiency of Galactose-1-P Uridyl Transferase
## Footnote
It can also be caused by deficiencies of Galactokinase or 4-Epimerase.
160
What are the symptoms of hereditary fructose intolerance?
Attacks of hypoglycemia and potential for death
## Footnote
This condition is caused by deficiency of Aldolase B in the liver.
161
Fill in the blank: The enzyme that converts Fructose-1-P to Dihydroxy Acetone Phosphate is called _______.
Aldolase B
162
True or False: The entry of galactose into cells is insulin-dependent.
False
## Footnote
Like fructose, galactose entry is not insulin-dependent.
