Podcast
Questions and Answers
How does antithrombin contribute to the regulation of blood clot formation?
How does antithrombin contribute to the regulation of blood clot formation?
- It inhibits the activation of blood coagulation factors in healthy tissues.
- It promotes the formation of clots throughout the body.
- It breaks down existing clots to prevent vessel blockage.
- It confines clot formation to the immediate vicinity of a wound. (correct)
In individuals with Wilson's disease, which of the following physiological processes is directly impaired due to a deficiency in plasma ceruloplasmin?
In individuals with Wilson's disease, which of the following physiological processes is directly impaired due to a deficiency in plasma ceruloplasmin?
- The body's primary carrier of copper, leading to hepatolenticular degeneration. (correct)
- The oxygen-carrying capacity of red blood cells.
- The body's ability to form blood clots.
- The transport of iron, leading to iron accumulation in tissues.
Which statement accurately describes the role of plasma proteins in maintaining fluid distribution between blood and tissues?
Which statement accurately describes the role of plasma proteins in maintaining fluid distribution between blood and tissues?
- Plasma proteins decrease hydrostatic pressure, promoting fluid retention in tissues.
- Plasma proteins decrease osmotic pressure in the blood, leading to fluid accumulation in circulation.
- Plasma proteins increase osmotic pressure in the blood, drawing fluid from tissues into circulation. (correct)
- Plasma proteins have no significant effect on fluid distribution.
What is the primary significance of diminished levels of plasma O-linked oligosaccharide chains on plasma proteins?
What is the primary significance of diminished levels of plasma O-linked oligosaccharide chains on plasma proteins?
What is the primary function of haptoglobin in protecting the kidneys from damage?
What is the primary function of haptoglobin in protecting the kidneys from damage?
Individuals with analbuminemia typically exhibit only moderate edema. What compensatory mechanism primarily offsets the expected severe disruption in osmotic balance?
Individuals with analbuminemia typically exhibit only moderate edema. What compensatory mechanism primarily offsets the expected severe disruption in osmotic balance?
How does ferroportin facilitate iron metabolism, and what is its primary function in this process?
How does ferroportin facilitate iron metabolism, and what is its primary function in this process?
What is the role of hephaestin in iron metabolism, and how does it facilitate the function of another key protein?
What is the role of hephaestin in iron metabolism, and how does it facilitate the function of another key protein?
Describe the role of hepcidin in systemic iron homeostasis and its effect on iron absorption and recycling.
Describe the role of hepcidin in systemic iron homeostasis and its effect on iron absorption and recycling.
How does the HFE protein, in conjunction with transferrin receptors, influence hepcidin expression in the liver?
How does the HFE protein, in conjunction with transferrin receptors, influence hepcidin expression in the liver?
What is the primary mechanism by which hereditary hemochromatosis leads to iron overload in affected individuals?
What is the primary mechanism by which hereditary hemochromatosis leads to iron overload in affected individuals?
Describe the mechanism by which interleukin-6 (IL-6) influences the synthesis of hepcidin during an inflammatory response.
Describe the mechanism by which interleukin-6 (IL-6) influences the synthesis of hepcidin during an inflammatory response.
How does alpha 1-Antiproteinase deficiency lead to the development of emphysema?
How does alpha 1-Antiproteinase deficiency lead to the development of emphysema?
How does a₂-macroglobulin function as a broad-spectrum protease inhibitor in the plasma?
How does a₂-macroglobulin function as a broad-spectrum protease inhibitor in the plasma?
In individuals undergoing long-term hemodialysis, how does the accumulation of β₂-microglobulin contribute to an increased risk of amyloidosis?
In individuals undergoing long-term hemodialysis, how does the accumulation of β₂-microglobulin contribute to an increased risk of amyloidosis?
One way antibody diversity arises is via the distribution of the coding sequence for each chain. Which is correct?
One way antibody diversity arises is via the distribution of the coding sequence for each chain. Which is correct?
Following exposure to an immunogen, class (isotype) switching refers to which of the following?
Following exposure to an immunogen, class (isotype) switching refers to which of the following?
What role do thioester bonds play in the function of both a₂-macroglobulin and the complement system?
What role do thioester bonds play in the function of both a₂-macroglobulin and the complement system?
Identify the primary mechanism by which the mannose-binding lectin (MBL) enhances the immune response.
Identify the primary mechanism by which the mannose-binding lectin (MBL) enhances the immune response.
What represents the difference in an adaptive and innate immune response?
What represents the difference in an adaptive and innate immune response?
Why does edema occur when the concentration of plasma proteins is significantly diminished?
Why does edema occur when the concentration of plasma proteins is significantly diminished?
How does the absence of albumin in individuals with analbuminemia primarily affect fluid distribution between blood and tissues?
How does the absence of albumin in individuals with analbuminemia primarily affect fluid distribution between blood and tissues?
What posttranslational modification accelerates the clearance of plasma glycoproteins from the circulation?
What posttranslational modification accelerates the clearance of plasma glycoproteins from the circulation?
What is the role of NRAMP1 in iron metabolism?
What is the role of NRAMP1 in iron metabolism?
How does hemopexin contribute to protecting the body from the harmful effects of free heme?
How does hemopexin contribute to protecting the body from the harmful effects of free heme?
What is the primary mechanism by which mutations in the HFE protein lead to hereditary hemochromatosis?
What is the primary mechanism by which mutations in the HFE protein lead to hereditary hemochromatosis?
What effect does increased hepcidin synthesis have on iron levels?
What effect does increased hepcidin synthesis have on iron levels?
Which of the following is a key characteristic of the alternative pathway in complement activation?
Which of the following is a key characteristic of the alternative pathway in complement activation?
What cellular mechanism leads to the diverse range of antibody specificities?
What cellular mechanism leads to the diverse range of antibody specificities?
How does hereditary aceruloplasminemia lead to the development of insulin-dependent diabetes and neurological degeneration?
How does hereditary aceruloplasminemia lead to the development of insulin-dependent diabetes and neurological degeneration?
How does transferrin receptor 2 (TfR2) differ from transferrin receptor 1 (TfR1) in regulating iron uptake?
How does transferrin receptor 2 (TfR2) differ from transferrin receptor 1 (TfR1) in regulating iron uptake?
In the context of iron metabolism, what is the role of duodenal cytochrome b (Dcytb)?
In the context of iron metabolism, what is the role of duodenal cytochrome b (Dcytb)?
What triggers the activation of NFkB, a key transcription factor in immune responses?
What triggers the activation of NFkB, a key transcription factor in immune responses?
How does the hypervariability in immunoglobulin CDRs contribute to the specificity of antibody-antigen interactions?
How does the hypervariability in immunoglobulin CDRs contribute to the specificity of antibody-antigen interactions?
What is the significance of the thioester bond in alpha-2 macroglobulin's mechanism of protease inhibition?
What is the significance of the thioester bond in alpha-2 macroglobulin's mechanism of protease inhibition?
How does the JAK-STAT pathway mediate the influence of inflammatory signals on hepcidin levels?
How does the JAK-STAT pathway mediate the influence of inflammatory signals on hepcidin levels?
In adaptive immunity, what role do T cells play in the body's defense mechanisms?
In adaptive immunity, what role do T cells play in the body's defense mechanisms?
Which mechanism explains how a newly synthesized light chain combines with different heavy chains to generate diverse antibody classes?
Which mechanism explains how a newly synthesized light chain combines with different heavy chains to generate diverse antibody classes?
How does the production of transthyretin fragments in familial amyloidosis lead to tissue damage?
How does the production of transthyretin fragments in familial amyloidosis lead to tissue damage?
What role do bone morphogenic proteins (BMPs) and hemojuvelin (HJV) play in hepcidin expression?
What role do bone morphogenic proteins (BMPs) and hemojuvelin (HJV) play in hepcidin expression?
What is the direct consequence of hepcidin binding to ferroportin?
What is the direct consequence of hepcidin binding to ferroportin?
In the blood coagulation cascade, what is the initial trigger in the classical pathway?
In the blood coagulation cascade, what is the initial trigger in the classical pathway?
Which of the following is a characteristic of the innate immune system?
Which of the following is a characteristic of the innate immune system?
Which of the following is true regarding iron?
Which of the following is true regarding iron?
What characterizes iron deficient anemia?
What characterizes iron deficient anemia?
Which component of hemoglobin facilitates the transit of transported iron?
Which component of hemoglobin facilitates the transit of transported iron?
How does serum amyloid P component contribute to amyloidosis?
How does serum amyloid P component contribute to amyloidosis?
How can MBL influence the classical pathway?
How can MBL influence the classical pathway?
Which plasma protein has been used in treatment against burns and hemorrhagic shock?
Which plasma protein has been used in treatment against burns and hemorrhagic shock?
How does the body use the blood in homeostasis?
How does the body use the blood in homeostasis?
Compared to other Immunoglobulins, what makes Immunoglobulin G abundant?
Compared to other Immunoglobulins, what makes Immunoglobulin G abundant?
Which of the following statements is true about haptoglobin?
Which of the following statements is true about haptoglobin?
How is hemochromatosis characterized?
How is hemochromatosis characterized?
What is the role of oxidation of Met358, a methionine residue on anti-trypsin proteases?
What is the role of oxidation of Met358, a methionine residue on anti-trypsin proteases?
What is the function of the complement system?
What is the function of the complement system?
What is responsible for the class-specific effector functions?
What is responsible for the class-specific effector functions?
How do interleukin factors of the innate immune system influence the immune system?
How do interleukin factors of the innate immune system influence the immune system?
What is a key role of the liver?
What is a key role of the liver?
In what way does the presence of acute-phase proteins, such as C-reactive protein (CRP), signify during instances of inflammation?
In what way does the presence of acute-phase proteins, such as C-reactive protein (CRP), signify during instances of inflammation?
What mechanism primarily accounts for the kidney's protection against damage due to hemoglobin release during red blood cell turnover?
What mechanism primarily accounts for the kidney's protection against damage due to hemoglobin release during red blood cell turnover?
How does ferroportin facilitate iron homeostasis in the body?
How does ferroportin facilitate iron homeostasis in the body?
What is the primary role of hephaestin in iron metabolism?
What is the primary role of hephaestin in iron metabolism?
Which statement best explains the role of hepcidin in the regulation of plasma iron levels?
Which statement best explains the role of hepcidin in the regulation of plasma iron levels?
How does the HFE protein influence hepcidin expression in the liver in response to changes in iron levels?
How does the HFE protein influence hepcidin expression in the liver in response to changes in iron levels?
What is the underlying mechanism in hereditary hemochromatosis that leads to iron overload?
What is the underlying mechanism in hereditary hemochromatosis that leads to iron overload?
How do inflammatory signals, particularly through interleukin-6 (IL-6), influence the production of hepcidin in the liver?
How do inflammatory signals, particularly through interleukin-6 (IL-6), influence the production of hepcidin in the liver?
What is the significance of Met358 oxidation in alpha 1-Antiproteinase concerning its function?
What is the significance of Met358 oxidation in alpha 1-Antiproteinase concerning its function?
In what manner does a₂-macroglobulin achieve broad-spectrum protease inhibition within the plasma?
In what manner does a₂-macroglobulin achieve broad-spectrum protease inhibition within the plasma?
How does the accumulation of β₂-microglobulin potentially contribute to amyloidosis in hemodialysis?
How does the accumulation of β₂-microglobulin potentially contribute to amyloidosis in hemodialysis?
What mechanism underlies the extensive diversity observed in immunoglobulin CDRs and how do they contribute to antibody-antigen recognition?
What mechanism underlies the extensive diversity observed in immunoglobulin CDRs and how do they contribute to antibody-antigen recognition?
In what manner does activation-induced cytidine deaminase (AID) augment antibody diversity?
In what manner does activation-induced cytidine deaminase (AID) augment antibody diversity?
In the context of adaptive immune responses and immunoglobulin production, what precisely does class switching entail?
In the context of adaptive immune responses and immunoglobulin production, what precisely does class switching entail?
What is the key function of bone morphogenic proteins and hemojuvelin concerning hepcidin expression?
What is the key function of bone morphogenic proteins and hemojuvelin concerning hepcidin expression?
How does transferrin receptor 2 (TfR2) regulate iron uptake compared to transferrin receptor 1 (TfR1)?
How does transferrin receptor 2 (TfR2) regulate iron uptake compared to transferrin receptor 1 (TfR1)?
What role does duodenal cytochrome b (Dcytb) perform in iron absorption?
What role does duodenal cytochrome b (Dcytb) perform in iron absorption?
How does NFκB activation contribute to modulating the immune response?
How does NFκB activation contribute to modulating the immune response?
What role does mannose-binding lectin (MBL) play in triggering the complement system?
What role does mannose-binding lectin (MBL) play in triggering the complement system?
How does hereditary aceruloplasminemia lead to neurological degeneration and insulin-dependent diabetes?
How does hereditary aceruloplasminemia lead to neurological degeneration and insulin-dependent diabetes?
What is the primary mechanism by which transthyretin mutations cause familial amyloidosis?
What is the primary mechanism by which transthyretin mutations cause familial amyloidosis?
Which is a plausible implication for mutations affecting the ZZ genotype (synthesize PiZ) of alpha-1 antiproteinase, concerning its physiological consequences?
Which is a plausible implication for mutations affecting the ZZ genotype (synthesize PiZ) of alpha-1 antiproteinase, concerning its physiological consequences?
In the context of iron metabolism, what is the impact of the increased levels of hepcidin in athletes?
In the context of iron metabolism, what is the impact of the increased levels of hepcidin in athletes?
Albumins facilitate the transit of hormones and lipids, but not of certain drugs between tissues.
Albumins facilitate the transit of hormones and lipids, but not of certain drugs between tissues.
Fibrinogen is a protein that is important for forming clots to seal injured vessels.
Fibrinogen is a protein that is important for forming clots to seal injured vessels.
Only certain autoimmune disorders, such as type 1 diabetes, result from the aberrant production of immunoglobulins.
Only certain autoimmune disorders, such as type 1 diabetes, result from the aberrant production of immunoglobulins.
The main function of blood is to transport oxygen from the lungs to the tissues and CO2 from the tissues to the lungs.
The main function of blood is to transport oxygen from the lungs to the tissues and CO2 from the tissues to the lungs.
The blood transports waste products for removal by the kidneys, but not by the lungs, skin, or intestines.
The blood transports waste products for removal by the kidneys, but not by the lungs, skin, or intestines.
Blood helps regulate body temperature by constricting the amount of body heat.
Blood helps regulate body temperature by constricting the amount of body heat.
Globulins, fibrinogen, and albumin are three types of proteins found in plasma.
Globulins, fibrinogen, and albumin are three types of proteins found in plasma.
Plasma proteins do not usually contain carbohydrate.
Plasma proteins do not usually contain carbohydrate.
A net outward force of about 20 mm Hg drives fluid from the plasma into the interstitial spaces.
A net outward force of about 20 mm Hg drives fluid from the plasma into the interstitial spaces.
Most plasma proteins, including albumin, transferrin, and fibrinogen are synthesized in the liver.
Most plasma proteins, including albumin, transferrin, and fibrinogen are synthesized in the liver.
Loss of terminal sialic acid residues decreases clearance of plasma glycoproteins from the circulation.
Loss of terminal sialic acid residues decreases clearance of plasma glycoproteins from the circulation.
The genes for plasma proteins lack the code for an amino-terminal signal sequence that targets them to the endoplasmic reticulum.
The genes for plasma proteins lack the code for an amino-terminal signal sequence that targets them to the endoplasmic reticulum.
In many humans, genetic mutations can cause the complete absence of albumin, a condition called analbuminemia, which results in extreme edema.
In many humans, genetic mutations can cause the complete absence of albumin, a condition called analbuminemia, which results in extreme edema.
Plasma levels of acute-phase proteins decrease during chronic inflammatory states and in patients with cancer.
Plasma levels of acute-phase proteins decrease during chronic inflammatory states and in patients with cancer.
Erythrocytes are phagocytosed in the liver and kidney by macrophages of the reticuloendothelial system (RES).
Erythrocytes are phagocytosed in the liver and kidney by macrophages of the reticuloendothelial system (RES).
Haptoglobin is a plasma glycoprotein that prevents kidney damage by binding extra-corpuscular hemoglobin and facilitating its excretion.
Haptoglobin is a plasma glycoprotein that prevents kidney damage by binding extra-corpuscular hemoglobin and facilitating its excretion.
The human body stores very little iron.
The human body stores very little iron.
Hepcidin reduces both iron absorption and its recycling.
Hepcidin reduces both iron absorption and its recycling.
Hereditary hemochromatosis is a genetic affliction that leads to a decrease in iron in the body.
Hereditary hemochromatosis is a genetic affliction that leads to a decrease in iron in the body.
Lectin refers to any protein that solely binds to mannose-containing carbohydrates.
Lectin refers to any protein that solely binds to mannose-containing carbohydrates.
Match each plasma protein with its primary role in iron homeostasis:
Match each plasma protein with its primary role in iron homeostasis:
Match the immunoglobulin class with its key role in the immune response:
Match the immunoglobulin class with its key role in the immune response:
Match each plasma protein with its function related to protease inhibition or blood coagulation:
Match each plasma protein with its function related to protease inhibition or blood coagulation:
Match each acute-phase protein with its role in inflammation or tissue damage:
Match each acute-phase protein with its role in inflammation or tissue damage:
Link each condition with the plasma protein that, when deficient, leads to its development:
Link each condition with the plasma protein that, when deficient, leads to its development:
Match the mechanism of iron uptake in enterocytes with the protein involved in that process:
Match the mechanism of iron uptake in enterocytes with the protein involved in that process:
Match each lipoprotein with its primary function:
Match each lipoprotein with its primary function:
Match the component of the classical complement pathway with its function:
Match the component of the classical complement pathway with its function:
Associate the iron regulatory proteins (IRPs) with their action on specific mRNAs when iron is low:
Associate the iron regulatory proteins (IRPs) with their action on specific mRNAs when iron is low:
Match given antibody with its appropriate description.
Match given antibody with its appropriate description.
Flashcards
Albumin functions
Albumin functions
Facilitate transit of fatty acids, steroid hormones, and other ligands between tissues.
Transferrin function
Transferrin function
Aids the uptake and distribution of iron in the body.
Fibrinogen function
Fibrinogen function
Building block of the fibrin mesh for the clots.
Antithrombin function
Antithrombin function
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α₁-antiproteinase and α₂-macroglobulin function
α₁-antiproteinase and α₂-macroglobulin function
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Antibodies function
Antibodies function
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Respiration function of blood
Respiration function of blood
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Nutrition function of blood
Nutrition function of blood
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Excretion function of blood
Excretion function of blood
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Water Balance function
Water Balance function
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Defense function of blood
Defense function of blood
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Hormone function of blood
Hormone function of blood
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Plasma proteins composition
Plasma proteins composition
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Where is albumin made?
Where is albumin made?
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What is the role of albumin?
What is the role of albumin?
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Role of albumin
Role of albumin
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Kwashiorkor
Kwashiorkor
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α₁-Antiproteinase
α₁-Antiproteinase
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α₁-Antiproteinase deficiency
α₁-Antiproteinase deficiency
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a₂-Macroglobulin
a₂-Macroglobulin
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What do aberrant production of immunoglobulins result in?
What do aberrant production of immunoglobulins result in?
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What are some functions of blood?
What are some functions of blood?
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Starling forces
Starling forces
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Half life
Half life
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Haptoglobin
Haptoglobin
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Ferritin.
Ferritin.
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Transferrin
Transferrin
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What is a function of blood?
What is a function of blood?
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Haptoglobin Role
Haptoglobin Role
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Ferritin.
Ferritin.
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Acid-base balance function of blood
Acid-base balance function of blood
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Body temperature regulation function
Body temperature regulation function
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Electrophoresis Fractions
Electrophoresis Fractions
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Edema
Edema
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Liver's role in blood
Liver's role in blood
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Signal Sequence
Signal Sequence
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Polymorphism
Polymorphism
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C-reactive protein (CRP)
C-reactive protein (CRP)
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Cytokines
Cytokines
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Nuclear factor kappa-B (NFkB)
Nuclear factor kappa-B (NFkB)
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Heme oxygenase
Heme oxygenase
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Ferroportin
Ferroportin
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Ceruloplasmin
Ceruloplasmin
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Hemosiderin
Hemosiderin
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TfR1 mRNA's 3' UTR
TfR1 mRNA's 3' UTR
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Hepcidin
Hepcidin
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Interleukin-6 (IL-6)
Interleukin-6 (IL-6)
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Anemia of inflammation (AI)
Anemia of inflammation (AI)
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Hemosiderosis
Hemosiderosis
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Amyloidosis
Amyloidosis
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Immunoglobulins
Immunoglobulins
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Immunoglobulin
Immunoglobulin
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IgG
IgG
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Hypervariable regions
Hypervariable regions
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Class (isotype) switching
Class (isotype) switching
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Membrane attack complex
Membrane attack complex
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Metabolism function of blood
Metabolism function of blood
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Coagulation function of blood
Coagulation function of blood
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NFkB activation
NFkB activation
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NRAMP1
NRAMP1
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Hypoceruloplasmenia
Hypoceruloplasmenia
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Aceruloplasminemia
Aceruloplasminemia
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Convert Fe3+ to Fe2+
Convert Fe3+ to Fe2+
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Binding Transferrin-iron Complex to TfR2
Binding Transferrin-iron Complex to TfR2
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BMP Binding
BMP Binding
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Cytokines to activate hepcidin
Cytokines to activate hepcidin
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Total iron binding capacity
Total iron binding capacity
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alpha 1-Antitrypsin
alpha 1-Antitrypsin
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What is the function of hepcidin?
What is the function of hepcidin?
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What is turnover?
What is turnover?
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What is hephaestin?
What is hephaestin?
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Mannose-binding Lectin (MBL)
Mannose-binding Lectin (MBL)
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What is amyloidosis?
What is amyloidosis?
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Oxidation of Fe2+ to Fe3+
Oxidation of Fe2+ to Fe3+
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Hereditary Hemochromatosis
Hereditary Hemochromatosis
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Fenton reaction
Fenton reaction
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Ceruloplasmin deficiency
Ceruloplasmin deficiency
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Mannose-binding lectin
Mannose-binding lectin
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Innate immune system
Innate immune system
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Adaptive immune system
Adaptive immune system
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Epitope
Epitope
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Hepcidin in systemic iron regulation
Hepcidin in systemic iron regulation
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Hemochromatosis
Hemochromatosis
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Study Notes
- Plasma proteins and immunoglobulins play crucial roles in human physiology.
Biomedical Importance
- Albumins transport fatty acids and steroid hormones between tissues
- Transferrin assists in iron uptake and distribution
- Fibrinogen is a building block for fibrin mesh in blood clots
- Antithrombin confines clot formation to the wound area
- α₁-antiproteinase and α₂-macroglobulin protect tissues from proteases
- Immunoglobulins, also called antibodies, form the body's immune system
- Perturbations in plasma protein production can lead to hemophilia, Wilson disease, and emphysema
- Autoimmune disorders like type 1 diabetes and rheumatoid arthritis can result from aberrant immunoglobulin production, prevalence rates of autoimmune diseases vary from 4 in 100,000 (Scleroderma) to 1152 in 100,000 (Graves Disease/hyperthyroidism)
- Immunocompromised individuals are vulnerable to infections due to protective antibody insufficiencies due to viral infections, or suppressed by drugs
- Blood coagulation factors are latent proteases, or zymogens
Functions of Blood
- Respiration: Transports O₂ from lungs to tissues and CO₂ from tissues to lungs
- Nutrition: Transports absorbed food materials
- Excretion: Transports metabolic waste to kidneys, lungs, skin, and intestines for removal
- Acid-base balance: Maintains normal acid-base balance
- Water balance: Regulates water exchange between circulating fluid & tissue fluid via effects of blood on water
- Temperature: Regulates body temperature by the distribution of body heat
- Defense: Protects against infection via white blood cells and circulating antibodies
- Hormones: Transports hormones; regulates metabolism
- Metabolites: Transports metabolites
- Coagulation: Blood clotting
Plasma Composition
- Plasma contains fibrinogen, albumin, and globulins
- Serum protein separates into albumin, α₁-, α₂-, β-, and γ-globulins during cellulose acetate zone electrophoresis
- Plasma proteins contain disulfide bonds, carbohydrates (glycoproteins), or lipids (lipoproteins)
Fluid Distribution
- Plasma protein concentration ranges from 7 to 7.5 g/dL
- Osmotic pressure is ~25 mm Hg. Also known as Oncotic pressure
- Hydrostatic pressure in arterioles forces fluid into interstitial spaces; ~37 mm Hg with an opposing interstitial pressure of 1 mmHg generating an outward force of roughly 11 mmHg
- Hydrostatic pressure in venules drives water back into circulation; ~17 mm Hg generating an inward force of roughly 9 mmHg
- Reduced protein concentration causes fluid accumulation in tissues, leading to edema, and are often referred to as Starling forces
Protein Synthesis
- The liver synthesizes 70-80% of plasma proteins including albumin, fibrinogen, and transferrin
- Exceptions include von Willebrand factor (vascular endothelium) and γ-globulins (lymphocytes)
- Most plasma proteins are modified via glycosylation which helps determine protein function
- Signal sequences target plasma proteins to the endoplasmic reticulum for secretion
- Posttranslational modifications occur in secretory vesicles before release into plasma
Protein Polymorphism
- Many plasma proteins display polymorphism (existence of multiple phenotypes in the population)
- Examples include α₁-antitrypsin, haptoglobin, transferrin, ceruloplasmin, and immunoglobulins
Protein Half-Life
- Plasma proteins have a characteristic half-life
- Turnover replaces older protein molecules with new ones
Albumin
- Liver synthesizes ~12 g of albumin per day accounting for 25% of hepatic protein production
- About 40% of the body's albumin circulates in the plasma.
- Albumin constitutes ~60% of total plasma protein (between 3.4-4.7 g/dL)
- Albumin contributes 75-80% of osmotic pressure of human plasma
- Albumin binds and transports fatty acids, steroid hormones, bilirubin, copper, and drugs
- Albumin is used to treat burns and hemorrhagic shock
- Analbuminemia (absence of albumin) leads to only moderate edema
- Reduced albumin synthesis occurs in liver diseases and protein malnutrition can decrease the ratio of albumin compared to globulins decreased albumin-globulin ratio
- Mature human albumin consists of a single polypeptide chain, 585 amino acids in length, that is organized into three functional domains
- Its ellipsoidal conformation is stabilized by a total of 17 intrachain disulfide bonds
Acute Phase Proteins
- Levels increase during inflammation/tissue damage
- Examples include C-reactive protein (CRP), α₁-antiproteinase, haptoglobin, α-acid glycoprotein
- CRP stimulates the complement pathway
- α₁-antitrypsin neutralizes proteases
- Cytokines (interleukins, interferons, tumor necrosis factors) facilitate cell-cell communication
- Interleukin 1 (IL-1) stimulates acute-phase protein synthesis
- Nuclear factor kappa-B (NFkB) regulates expression of genes encoding cytokines and cell adhesion molecules
###Haptoglobin
- Erythrocytes are catabolized (~200 billion per day)
- Iron is recycled by macrophages
- Haptoglobin (Hp) prevents kidney damage from hemoglobin precipitates
- Hemoglobin-haptoglobin complex prevents passage through glomerulus; Hb-Hp is greater than or equal to 155 kDa
Haptoglobin Polymorphism
- Haptoglobin has three polymorphic forms (Hp 1-1, Hp 2-1, Hp 2-2)
- Haptoglobin levels drop during hemolytic anemias
- Haptoglobin-related protein is elevated in some cancer patients
Iron Metabolism
- Iron is conserved
- The body loses 1-1.5 mg of iron per day
- Enterocytes absorb ferrous iron (Fe²⁺)
- Ferric iron (Fe³⁺) conversion by duodenal cytochrome b (Dcytb)
Iron Transport
- Divalent metal transporter 1 (DMT1) transports iron across the apical membrane
- Iron is stored as ferritin or transferred by ferroportin
- Hephaestin oxidizes Fe²⁺ to Fe³⁺
- Transferrin transports iron in blood
Ferritin
- Ferritin stores iron (up to 4500 ferric atoms)
- H subunits of ferritin possess ferroxidase activity
- The Mw is 440 kDa
- 24 subunits of 19 - 21 kDa polypeptides form a hollow ball that encapsulates 3000 - 4500 atoms
- Hemosiderin (partially degraded ferritin) appears in iron overload conditions
Transferrin and Ceruloplasmin
- Transferrin transports Fe 3+
- Transferrin is a beta 1-globulin
- Ceruloplasmin contains 6 copper atoms
- glycosylation of transferrin is impaired in congenital disorders of glycosylation and chronic alcoholism
- Toxicity is linked to formation of ROS (Reactive Oxygen Species)
- Transferrin concentration in plasma is approximately 300 mg/dL, representing the total iron-binding capacity (TIBC)
- The transferrin cycle involves receptor-mediated endocytosis and iron release in late endosomes
- Ceruloplasmin oxidizes Fe²⁺ to Fe³⁺
- Ceruloplasmin deficiency leads to iron accumulation in tissues
Iron Homeostasis
- Hypoceruloplasmenia (genetic condition with ~50% ceruloplasmin levels) shows minimal clinical abnormalities
- Aceruloplasminemia (abolished ferroxidase activity) can have severe effects
Iron Regulation
- Iron levels regulate transferrin receptor and ferritin synthesis
- HFE protein and BMPs influence hepcidin expression
- the binding affinity of BMPR is augmented when associated with coreceptor hemojuvelin (HJV) BMPR-HJV complex triggers the phosphorylation of SMADs
- Cytokines induce hepcidin synthesis during inflammation
- Hepcidin decreases during hypoxia or β-thalassemia
Iron-Related Diseases
- Iron deficiency: results in hypochromic, microcytic anemia with clinical biomarkers
- serum ferritin decreasing to <15 ug/dL
- total iron binding capacity increasing to >400 ug/dL
- serum iron decreasing to < 30 ug/dL
- transferrin saturation decreasing to <10%
- RBC protoporphyrin increasing
- Hereditary hemochromatosis: characterized by iron overload; can be caused by mutations in genes for encoding the homeostatic iron regulator protein, hepcidin, TfR2, HJV or ferroportin
Protease Inhibitors
- Proteases (e.g., α₁-antiproteinase, α₂-macroglobulin) prevent indiscriminate proteolysis
a1-Antiproteinase
- Alpha 1-Antiproteinase, a glycoprotein, is a serine protease inhibitor, functions as alpha 1-antitrypsin.
- Deficiencies contributes to emphysema and liver disease a1-Antiproteinase: a 394 residue glycoprotein
α2-Macroglobulin
- Functions include neutralizes proteases, and transports cytokines to tissues
- Alpha 2-Macroglobulin: 8 to 10% of total plasma portein, synthesized by monocytes, hepatocytes, and astrocytes; a homotetrameric glycoprotein synthesized
Amyloidosis
- The result of from deposition of plasma proteins in tissues resulting in impaired tissue function
Immunoglobulins
- Immunlgobulins defend against invaders
- Includes B lymphocytes (B cells), T lymphocytes (T cells), and the innate immune system
- The five classes are IgA, IgD, IgE, IgG, and IgM.
- The most abundant of the five, IgG, consists of two identical light chains (23 kDa) linked together by a network of disulfide bonds to each other as well as two identical heavy chains (53-75 kDa)
- Use light and heavy chains
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