Podcast
Questions and Answers
What is the main function of the extracellular matrix in organs?
What is the main function of the extracellular matrix in organs?
What is the primary component of the non-fibrous ground substance in the extracellular matrix?
What is the primary component of the non-fibrous ground substance in the extracellular matrix?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the role of hydroxyproline in collagen?
What is the role of hydroxyproline in collagen?
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What is the characteristic shape of the α-chains in collagen?
What is the characteristic shape of the α-chains in collagen?
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What is the function of pyrrolidone rings in collagen?
What is the function of pyrrolidone rings in collagen?
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What is the approximate molecular weight of a collagen triple helix?
What is the approximate molecular weight of a collagen triple helix?
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What is the conformation of the collagen triple helix?
What is the conformation of the collagen triple helix?
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What is the role of hydroxylysine in collagen?
What is the role of hydroxylysine in collagen?
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What is the strength of the collagen triple helix compared to steel?
What is the strength of the collagen triple helix compared to steel?
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What is the primary function of elastin in connective tissue?
What is the primary function of elastin in connective tissue?
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What is the role of lysyl oxidase in collagen synthesis?
What is the role of lysyl oxidase in collagen synthesis?
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What is the primary difference between collagen and elastin?
What is the primary difference between collagen and elastin?
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What is the function of fibronectin in the ECM?
What is the function of fibronectin in the ECM?
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What is the result of defects in the glomerular basement membrane?
What is the result of defects in the glomerular basement membrane?
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What is the role of glycosaminoglycans in the ECM?
What is the role of glycosaminoglycans in the ECM?
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What is the function of proteoglycans in the ECM?
What is the function of proteoglycans in the ECM?
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What is the result of defects in GAG degradation?
What is the result of defects in GAG degradation?
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What is the role of matrix metalloproteinases in the ECM?
What is the role of matrix metalloproteinases in the ECM?
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What is the function of integrins in the ECM?
What is the function of integrins in the ECM?
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What is the primary mechanism by which MMP activity is regulated?
What is the primary mechanism by which MMP activity is regulated?
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What is the consequence of destroying the ECM by MMPs?
What is the consequence of destroying the ECM by MMPs?
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What is the role of TIMPs in MMP activity?
What is the role of TIMPs in MMP activity?
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Why do cancer cells that metastasize require MMP activity?
Why do cancer cells that metastasize require MMP activity?
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What is the consequence of dysregulation of MMP activity?
What is the consequence of dysregulation of MMP activity?
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What is the role of α2-macroglobulin in MMP activity?
What is the role of α2-macroglobulin in MMP activity?
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What is the primary function of MMPs in cell movement?
What is the primary function of MMPs in cell movement?
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What is the consequence of coordinated expression of MMPs and TIMPs?
What is the consequence of coordinated expression of MMPs and TIMPs?
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What is the primary function of ECM remodeling in cell movement?
What is the primary function of ECM remodeling in cell movement?
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What is the role of MMPs in cancer cell metastasis?
What is the role of MMPs in cancer cell metastasis?
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What is the primary mechanism by which MMPs break down the ECM?
What is the primary mechanism by which MMPs break down the ECM?
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What is the result of coordinated expression of MMPs and TIMPs?
What is the result of coordinated expression of MMPs and TIMPs?
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What is the role of TIMPs in MMP activity?
What is the role of TIMPs in MMP activity?
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What is the consequence of dysregulation of MMP activity?
What is the consequence of dysregulation of MMP activity?
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What is the role of α2-macroglobulin in MMP activity?
What is the role of α2-macroglobulin in MMP activity?
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Why do cancer cells that metastasize require MMP activity?
Why do cancer cells that metastasize require MMP activity?
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What is the result of MMPs breaking down the ECM?
What is the result of MMPs breaking down the ECM?
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What is the role of MMPs in cell movement?
What is the role of MMPs in cell movement?
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What is the consequence of unregulated ECM destruction?
What is the consequence of unregulated ECM destruction?
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What is the importance of coordinated MMP and TIMP expression?
What is the importance of coordinated MMP and TIMP expression?
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What is the primary function of proteoglycans in osteoarthritis?
What is the primary function of proteoglycans in osteoarthritis?
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Which of the following proteoglycans is implicated in rheumatoid arthritis?
Which of the following proteoglycans is implicated in rheumatoid arthritis?
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What is the consequence of increased proteoglycan degradation in osteoarthritis?
What is the consequence of increased proteoglycan degradation in osteoarthritis?
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Which of the following is NOT a characteristic of proteoglycans in osteoarthritis?
Which of the following is NOT a characteristic of proteoglycans in osteoarthritis?
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What is the role of proteoglycans in the progression of osteoarthritis?
What is the role of proteoglycans in the progression of osteoarthritis?
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Which of the following proteoglycans is involved in the pathogenesis of rheumatoid arthritis?
Which of the following proteoglycans is involved in the pathogenesis of rheumatoid arthritis?
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What is the consequence of altered proteoglycan synthesis in osteoarthritis?
What is the consequence of altered proteoglycan synthesis in osteoarthritis?
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Which of the following is a characteristic of proteoglycans in osteoarthritis?
Which of the following is a characteristic of proteoglycans in osteoarthritis?
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What is the role of proteoglycans in the development of osteoarthritis?
What is the role of proteoglycans in the development of osteoarthritis?
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Which of the following is a consequence of proteoglycan degradation in osteoarthritis?
Which of the following is a consequence of proteoglycan degradation in osteoarthritis?
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What is the primary function of the extracellular matrix in organs?
What is the primary function of the extracellular matrix in organs?
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What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
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What is the role of hydroxyproline in collagen?
What is the role of hydroxyproline in collagen?
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What is the composition of the non-fibrous ground substance in the extracellular matrix?
What is the composition of the non-fibrous ground substance in the extracellular matrix?
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What is the function of fibronectin in the ECM?
What is the function of fibronectin in the ECM?
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What is the role of collagen in the ECM?
What is the role of collagen in the ECM?
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What is the characteristic feature of the α-chains in collagen?
What is the characteristic feature of the α-chains in collagen?
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What is the function of laminin in the ECM?
What is the function of laminin in the ECM?
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What is the role of elastin in the ECM?
What is the role of elastin in the ECM?
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What is the primary component of the fibrous proteins in the ECM?
What is the primary component of the fibrous proteins in the ECM?
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What is the primary function of fibronectin in collagen fiber aggregation?
What is the primary function of fibronectin in collagen fiber aggregation?
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Which glycosaminoglycan is involved in the regulation of tumor cell migration?
Which glycosaminoglycan is involved in the regulation of tumor cell migration?
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What is the primary mechanism of MMP regulation of ECM proteins?
What is the primary mechanism of MMP regulation of ECM proteins?
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Which proteoglycan is an autoantigen in rheumatoid arthritis?
Which proteoglycan is an autoantigen in rheumatoid arthritis?
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What is the primary role of glycosaminoglycans in skin aging?
What is the primary role of glycosaminoglycans in skin aging?
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What is the primary function of elastin in connective tissue?
What is the primary function of elastin in connective tissue?
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Which enzyme is involved in the degradation of aggrecan in osteoarthritis?
Which enzyme is involved in the degradation of aggrecan in osteoarthritis?
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What is the primary function of laminin in the ECM?
What is the primary function of laminin in the ECM?
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Which type of collagen is involved in the formation of skin and bone?
Which type of collagen is involved in the formation of skin and bone?
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What is the primary function of fibromodulin in the ECM?
What is the primary function of fibromodulin in the ECM?
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What is the primary mechanism by which MMPs are regulated in the ECM?
What is the primary mechanism by which MMPs are regulated in the ECM?
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What is the consequence of dysregulation of MMP activity in the ECM?
What is the consequence of dysregulation of MMP activity in the ECM?
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What is the role of coordinated expression of MMPs and TIMPs in the ECM?
What is the role of coordinated expression of MMPs and TIMPs in the ECM?
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What is the result of destroying the ECM by MMPs?
What is the result of destroying the ECM by MMPs?
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Why do cancer cells that metastasize require extensive ECM remodeling?
Why do cancer cells that metastasize require extensive ECM remodeling?
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What is the role of TIMPs in regulating MMP activity in the ECM?
What is the role of TIMPs in regulating MMP activity in the ECM?
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What is the consequence of unregulated ECM destruction?
What is the consequence of unregulated ECM destruction?
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What is the primary function of α2-macroglobulin in regulating MMP activity?
What is the primary function of α2-macroglobulin in regulating MMP activity?
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What is the role of MMPs in releasing bound growth factors in the ECM?
What is the role of MMPs in releasing bound growth factors in the ECM?
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What is the consequence of dysregulation of MMP activity in cancer cells?
What is the consequence of dysregulation of MMP activity in cancer cells?
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What is the primary function of the extracellular matrix in organs?
What is the primary function of the extracellular matrix in organs?
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What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
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What is the role of hydroxyproline in collagen?
What is the role of hydroxyproline in collagen?
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What is the approximate molecular weight of a collagen triple helix?
What is the approximate molecular weight of a collagen triple helix?
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What is the primary component of the non-fibrous ground substance in the extracellular matrix?
What is the primary component of the non-fibrous ground substance in the extracellular matrix?
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What is the role of pyrrolidone rings in collagen?
What is the role of pyrrolidone rings in collagen?
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What is the characteristic feature of the α-chains in collagen?
What is the characteristic feature of the α-chains in collagen?
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What is the function of fibronectin in the extracellular matrix?
What is the function of fibronectin in the extracellular matrix?
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What is the role of hydroxylysine in collagen?
What is the role of hydroxylysine in collagen?
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What is the primary function of elastin in connective tissue?
What is the primary function of elastin in connective tissue?
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What is the primary mechanism by which MMPs regulate ECM proteins?
What is the primary mechanism by which MMPs regulate ECM proteins?
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Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
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What is the role of hyaluronic acid in tumor cell migration?
What is the role of hyaluronic acid in tumor cell migration?
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What is the primary function of aggrecanase in osteoarthritis?
What is the primary function of aggrecanase in osteoarthritis?
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What is the consequence of increased glycosaminoglycan degradation in skin aging?
What is the consequence of increased glycosaminoglycan degradation in skin aging?
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How do MMPs regulate ECM proteins?
How do MMPs regulate ECM proteins?
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What is the role of glycosaminoglycans in skin aging?
What is the role of glycosaminoglycans in skin aging?
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Which of the following proteoglycans is involved in the pathogenesis of osteoarthritis?
Which of the following proteoglycans is involved in the pathogenesis of osteoarthritis?
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What is the primary function of matrix metalloproteinases in the ECM?
What is the primary function of matrix metalloproteinases in the ECM?
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What is the consequence of unregulated ECM destruction in osteoarthritis?
What is the consequence of unregulated ECM destruction in osteoarthritis?
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What is the primary function of glycosaminoglycans in skin aging?
What is the primary function of glycosaminoglycans in skin aging?
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Which proteoglycan is an autoantigen in rheumatoid arthritis?
Which proteoglycan is an autoantigen in rheumatoid arthritis?
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How do matrix metalloproteinases regulate ECM proteins?
How do matrix metalloproteinases regulate ECM proteins?
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What is the role of hyaluronic acid in tumor cell migration?
What is the role of hyaluronic acid in tumor cell migration?
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What is the role of aggrecanase in osteoarthritis?
What is the role of aggrecanase in osteoarthritis?
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What is the primary function of proteoglycans in the ECM?
What is the primary function of proteoglycans in the ECM?
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Which of the following is a characteristic of glycosaminoglycans?
Which of the following is a characteristic of glycosaminoglycans?
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What is the primary function of matrix metalloproteinases in the ECM?
What is the primary function of matrix metalloproteinases in the ECM?
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What is the role of fibronectin in the ECM?
What is the role of fibronectin in the ECM?
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What is the consequence of defects in the glomerular basement membrane?
What is the consequence of defects in the glomerular basement membrane?
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Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
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What is the primary mechanism by which matrix metalloproteinases regulate ECM proteins?
What is the primary mechanism by which matrix metalloproteinases regulate ECM proteins?
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What is the role of hyaluronic acid in tumor cell migration?
What is the role of hyaluronic acid in tumor cell migration?
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What is the role of aggrecanase in osteoarthritis?
What is the role of aggrecanase in osteoarthritis?
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Which of the following is a characteristic of glycosaminoglycans in skin aging?
Which of the following is a characteristic of glycosaminoglycans in skin aging?
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What is the role of matrix metalloproteinases in the degradation of ECM proteins?
What is the role of matrix metalloproteinases in the degradation of ECM proteins?
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What is the consequence of altered proteoglycan synthesis in osteoarthritis?
What is the consequence of altered proteoglycan synthesis in osteoarthritis?
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What is the role of hyaluronic acid in ECM?
What is the role of hyaluronic acid in ECM?
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What is the consequence of unregulated ECM destruction?
What is the consequence of unregulated ECM destruction?
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Which of the following is a consequence of dysregulation of MMP activity?
Which of the following is a consequence of dysregulation of MMP activity?
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What is the primary role of MMPs in cell movement?
What is the primary role of MMPs in cell movement?
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What is the consequence of coordinated expression of MMPs and TIMPs?
What is the consequence of coordinated expression of MMPs and TIMPs?
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Which of the following is a mechanism of MMP activity regulation?
Which of the following is a mechanism of MMP activity regulation?
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What is the role of MMPs in ECM remodeling?
What is the role of MMPs in ECM remodeling?
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What is the consequence of ECM destruction by MMPs?
What is the consequence of ECM destruction by MMPs?
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Which of the following is a characteristic of cancer cells that metastasize?
Which of the following is a characteristic of cancer cells that metastasize?
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What is the role of TIMPs in ECM remodeling?
What is the role of TIMPs in ECM remodeling?
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What is the consequence of unregulated ECM destruction?
What is the consequence of unregulated ECM destruction?
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What is the primary function of MMPs in the ECM?
What is the primary function of MMPs in the ECM?
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What percentage of the proteins in the human body is comprised of collagen?
What percentage of the proteins in the human body is comprised of collagen?
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What is the approximate molecular weight of a collagen triple helix?
What is the approximate molecular weight of a collagen triple helix?
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What amino acid is only found at very tight junctions between α-chains in collagen?
What amino acid is only found at very tight junctions between α-chains in collagen?
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What is the primary function of the pyrrolidone rings in collagen?
What is the primary function of the pyrrolidone rings in collagen?
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What is the approximate percentage of glycine in collagen?
What is the approximate percentage of glycine in collagen?
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What is the site of O-glycosidic linkages in collagen?
What is the site of O-glycosidic linkages in collagen?
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What is the repetitive amino acid sequence found in collagen?
What is the repetitive amino acid sequence found in collagen?
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What is the function of hydroxyproline in collagen?
What is the function of hydroxyproline in collagen?
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What is the characteristic feature of the secondary structure of collagen?
What is the characteristic feature of the secondary structure of collagen?
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What is the role of the ECM in organs?
What is the role of the ECM in organs?
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What is the result of coordinated expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases?
What is the result of coordinated expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases?
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Which of the following glycoproteins plays a crucial role in cell adhesion and migration?
Which of the following glycoproteins plays a crucial role in cell adhesion and migration?
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What is the primary component of the fibrous proteins in the ECM?
What is the primary component of the fibrous proteins in the ECM?
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Which of the following is NOT a characteristic feature of glycosaminoglycans?
Which of the following is NOT a characteristic feature of glycosaminoglycans?
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What is the result of defects in the glomerular basement membrane?
What is the result of defects in the glomerular basement membrane?
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Which type of collagen is involved in the formation of skin and bone?
Which type of collagen is involved in the formation of skin and bone?
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What is the primary mechanism by which matrix metalloproteinases regulate ECM proteins?
What is the primary mechanism by which matrix metalloproteinases regulate ECM proteins?
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Which of the following is an autoantigen in rheumatoid arthritis?
Which of the following is an autoantigen in rheumatoid arthritis?
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What is the consequence of unregulated ECM degradation in osteoarthritis?
What is the consequence of unregulated ECM degradation in osteoarthritis?
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Which of the following is NOT a function of proteoglycans?
Which of the following is NOT a function of proteoglycans?
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What is the primary function of the extracellular matrix in organs?
What is the primary function of the extracellular matrix in organs?
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What is the characteristic feature of the repetitive amino acid sequence found in collagen?
What is the characteristic feature of the repetitive amino acid sequence found in collagen?
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What is the consequence of the closely packed left-handed alpha-chains in collagen?
What is the consequence of the closely packed left-handed alpha-chains in collagen?
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What is the primary component of the non-fibrous ground substance in the extracellular matrix?
What is the primary component of the non-fibrous ground substance in the extracellular matrix?
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What is the characteristic feature of the collagen triple helix?
What is the characteristic feature of the collagen triple helix?
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Which of the following types of collagen is NOT a fibril-forming collagen?
Which of the following types of collagen is NOT a fibril-forming collagen?
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What is the primary function of lysyl oxidase in collagen synthesis?
What is the primary function of lysyl oxidase in collagen synthesis?
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Which of the following proteins is responsible for providing a scaffold for elastin deposition?
Which of the following proteins is responsible for providing a scaffold for elastin deposition?
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What is the primary consequence of defects in GAG degradation?
What is the primary consequence of defects in GAG degradation?
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Which of the following is a characteristic feature of glycosaminoglycans?
Which of the following is a characteristic feature of glycosaminoglycans?
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What is the primary function of integrins in the ECM?
What is the primary function of integrins in the ECM?
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Which of the following is a consequence of increased proteoglycan degradation in osteoarthritis?
Which of the following is a consequence of increased proteoglycan degradation in osteoarthritis?
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What is the primary function of matrix metalloproteinases in the ECM?
What is the primary function of matrix metalloproteinases in the ECM?
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Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
Which of the following proteoglycans is an autoantigen in rheumatoid arthritis?
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What is the primary role of laminin in the ECM?
What is the primary role of laminin in the ECM?
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What is the primary mechanism by which MMPs release bound growth factors?
What is the primary mechanism by which MMPs release bound growth factors?
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What is the consequence of dysregulation of MMP activity in certain diseases?
What is the consequence of dysregulation of MMP activity in certain diseases?
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What is the primary function of coordinated expression of MMPs and TIMPs?
What is the primary function of coordinated expression of MMPs and TIMPs?
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What is the primary mechanism by which α2-macroglobulin regulates MMP activity?
What is the primary mechanism by which α2-macroglobulin regulates MMP activity?
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What is the primary requirement for cell movement within the ECM?
What is the primary requirement for cell movement within the ECM?
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What is the primary function of the unique conformation of the three α-chains in collagen?
What is the primary function of the unique conformation of the three α-chains in collagen?
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Which amino acid is always found at the very tight junctions between α-chains in collagen?
Which amino acid is always found at the very tight junctions between α-chains in collagen?
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What is the consequence of the high degree of tensile strength in collagen?
What is the consequence of the high degree of tensile strength in collagen?
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What is the role of pyrrolidone rings in collagen?
What is the role of pyrrolidone rings in collagen?
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What is the characteristic feature of the secondary structure of collagen?
What is the characteristic feature of the secondary structure of collagen?
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What is the approximate molecular weight of a collagen triple helix?
What is the approximate molecular weight of a collagen triple helix?
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What is the primary mechanism by which MMPs regulate ECM proteins?
What is the primary mechanism by which MMPs regulate ECM proteins?
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Dysregulation of MMP activity is associated with which of the following disorders?
Dysregulation of MMP activity is associated with which of the following disorders?
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What is the primary function of coordinated expression of MMPs and TIMPs?
What is the primary function of coordinated expression of MMPs and TIMPs?
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What is the role of α2-macroglobulin in MMP activity?
What is the role of α2-macroglobulin in MMP activity?
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What is the primary consequence of destroying the ECM by MMPs?
What is the primary consequence of destroying the ECM by MMPs?
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What is the primary function of collagen in relation to its structure?
What is the primary function of collagen in relation to its structure?
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Which proteoglycan is involved in the progression of osteoarthritis and is an autoantigen in rheumatoid arthritis?
Which proteoglycan is involved in the progression of osteoarthritis and is an autoantigen in rheumatoid arthritis?
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What is the consequence of deficiencies in vitamin C and copper in relation to collagen synthesis?
What is the consequence of deficiencies in vitamin C and copper in relation to collagen synthesis?
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What is the role of fibronectin in relation to cell behavior and ECM structure?
What is the role of fibronectin in relation to cell behavior and ECM structure?
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What is the primary function of lysyl oxidase in relation to collagen synthesis?
What is the primary function of lysyl oxidase in relation to collagen synthesis?
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What is the characteristic feature of the α-chains in collagen?
What is the characteristic feature of the α-chains in collagen?
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What is the role of matrix metalloproteinases in ECM remodeling and degradation?
What is the role of matrix metalloproteinases in ECM remodeling and degradation?
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What is the consequence of genetic defects in elastin and fibrillin?
What is the consequence of genetic defects in elastin and fibrillin?
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What is the primary function of glycosaminoglycans in relation to tissue turgor?
What is the primary function of glycosaminoglycans in relation to tissue turgor?
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What is the role of fibronectin in cell adhesion and migration?
What is the role of fibronectin in cell adhesion and migration?
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What is the primary function of integrins in the ECM?
What is the primary function of integrins in the ECM?
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What is the consequence of defects in the synthesis of fibrillin?
What is the consequence of defects in the synthesis of fibrillin?
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Which glycoprotein is responsible for forming the basal lamina in the ECM?
Which glycoprotein is responsible for forming the basal lamina in the ECM?
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What is the primary function of glycosaminoglycans in the ECM?
What is the primary function of glycosaminoglycans in the ECM?
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Which type of collagen is found in cartilage and bone?
Which type of collagen is found in cartilage and bone?
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What is the consequence of defects in the glomerular basement membrane?
What is the consequence of defects in the glomerular basement membrane?
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What is the primary function of matrix metalloproteinases in the ECM?
What is the primary function of matrix metalloproteinases in the ECM?
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Which protein is responsible for providing a scaffold for elastin deposition?
Which protein is responsible for providing a scaffold for elastin deposition?
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What is the primary function of proteoglycans in the ECM?
What is the primary function of proteoglycans in the ECM?
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What is the characteristic feature of the secondary structure of collagen?
What is the characteristic feature of the secondary structure of collagen?
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What is the primary mechanism by which MMPs facilitate tissue growth?
What is the primary mechanism by which MMPs facilitate tissue growth?
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What is the biological consequence of dysregulation of MMP activity in the ECM?
What is the biological consequence of dysregulation of MMP activity in the ECM?
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What is the primary function of coordinated expression of MMPs and TIMPs in the ECM?
What is the primary function of coordinated expression of MMPs and TIMPs in the ECM?
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How do cancer cells utilize MMP activity during metastasis?
How do cancer cells utilize MMP activity during metastasis?
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What is the primary mechanism by which MMPs facilitate cell movement within the ECM?
What is the primary mechanism by which MMPs facilitate cell movement within the ECM?
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What is the approximate molecular weight of the collagen triple helix?
What is the approximate molecular weight of the collagen triple helix?
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What is the primary function of the ECM in organs?
What is the primary function of the ECM in organs?
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What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
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What is the role of hydroxylysine in collagen?
What is the role of hydroxylysine in collagen?
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What is the composition of the non-fibrous ground substance in the ECM?
What is the composition of the non-fibrous ground substance in the ECM?
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What is the percentage of glycine in collagen?
What is the percentage of glycine in collagen?
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What is the primary mechanism by which coordinated expression of MMPs and TIMPs regulates tissue growth?
What is the primary mechanism by which coordinated expression of MMPs and TIMPs regulates tissue growth?
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What is the consequence of dysregulation of MMP activity in certain clinical disorders?
What is the consequence of dysregulation of MMP activity in certain clinical disorders?
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What is the role of MMPs in cell movement within the ECM?
What is the role of MMPs in cell movement within the ECM?
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What is the primary mechanism by which TIMPs regulate MMP activity?
What is the primary mechanism by which TIMPs regulate MMP activity?
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What is the role of MMPs in the release of growth factors during tissue growth?
What is the role of MMPs in the release of growth factors during tissue growth?
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What is the primary mechanism by which proteoglycans regulate tissue hydration in skin?
What is the primary mechanism by which proteoglycans regulate tissue hydration in skin?
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Which of the following amino acids is responsible for the high degree of tensile strength in collagen?
Which of the following amino acids is responsible for the high degree of tensile strength in collagen?
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What is the characteristic feature of the repetitive amino acid sequence in collagen?
What is the characteristic feature of the repetitive amino acid sequence in collagen?
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What is the primary function of fibronectin in the extracellular matrix?
What is the primary function of fibronectin in the extracellular matrix?
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What is the primary role of glycosaminoglycans in skin aging?
What is the primary role of glycosaminoglycans in skin aging?
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What is the characteristic feature of the collagen triple helix?
What is the characteristic feature of the collagen triple helix?
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What is the primary mechanism by which glycosaminoglycans contribute to tissue turgor?
What is the primary mechanism by which glycosaminoglycans contribute to tissue turgor?
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Which of the following glycosaminoglycans is most implicated in skin aging?
Which of the following glycosaminoglycans is most implicated in skin aging?
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What is the primary function of glycosaminoglycans in the ECM?
What is the primary function of glycosaminoglycans in the ECM?
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What is the consequence of defects in glycosaminoglycan degradation?
What is the consequence of defects in glycosaminoglycan degradation?
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Which of the following proteoglycans is most implicated in skin aging?
Which of the following proteoglycans is most implicated in skin aging?
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What is the primary function of glycosaminoglycans in cell behavior and tissue development?
What is the primary function of glycosaminoglycans in cell behavior and tissue development?
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Which of the following glycosaminoglycans is most involved in tumor cell migration?
Which of the following glycosaminoglycans is most involved in tumor cell migration?
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What is the primary mechanism by which glycosaminoglycans bind to cations or polycations?
What is the primary mechanism by which glycosaminoglycans bind to cations or polycations?
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Which of the following proteoglycans is most implicated in fibrosis?
Which of the following proteoglycans is most implicated in fibrosis?
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What is the primary function of glycosaminoglycans in the ECM during aging?
What is the primary function of glycosaminoglycans in the ECM during aging?
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Study Notes
Extracellular Matrix (ECM)
- Consists of fibrous proteins (collagen, elastin, and fibrillin) and non-fibrous ground substance (proteoglycans)
- Composition varies in tissues depending on their functions
- ECM protects organs, provides elasticity, and keeps cells and molecules from moving to other locations
- Provides a porous pathway for nutrient and oxygen diffusion to individual cells
Collagen
- The most abundant fibrous protein (~25% of human body proteins)
- Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
- At least 28 distinct polypeptide chains, encoded by separate genes
- Characterized by repetitive amino acid sequence and regular secondary structure
- High degree of tensile strength
Collagen Structure
- Three α-chains with different amino acid sequences
- Each α-chain has ~1000 amino acids, forms a left-handed helix, and has a specific sequence of glycine, proline, and hydroxyproline
- Pyrrolidone rings permit sharp twisting and confer rigidity
- Hydroxyproline contributes to H-bonding between α-chains
Collagen Triple Helix (Tropocollagen)
- Three α-chains wind around each other in a unique conformation
- Rod-like molecule with a length of 300 nm and a thickness of 1.5 nm
- α-chains are H-bonded, and the superhelix is resistant to unwinding
- Stabilized by unusual covalent cross-links within and between the triple helical units
Collagen Synthesis and Post-Translational Modification
- Occurs intracellularly in fibroblasts
- Involves hydroxylation of proline and lysine residues, and glycosylation of some hydroxylysines
- Procollagen is converted to tropocollagen, which is then cleaved to form collagen fibrils
Collagen Fibrils
- Formed by the self-assembly of tropocollagen molecules
- Have a quarter-staggered alignment and are cross-linked for strength
- Areas with complete overlap of the molecules alternate with areas with a gap
Fibronectin
- A secreted protein that binds collagen fibers during aggregation
- Alters the kinetics of fiber formation
- Interacts with proteoglycans to regulate the formation and orientation of collagen fibers
Elastin
- A connective tissue protein responsible for extensibility and elastic recoil
- Found in large amounts in lung, blood vessels, and elastic ligaments
- Has a highly cross-linked, amorphous structure with random coil conformations
- Tetrafunctional cross-links (desmosine) are unique to elastin
Elastin Synthesis
- Synthesized as a soluble monomer (tropoelastin)
- Cross-linked by lysyl oxidase to generate a fibrous mesh
- The mature cross-linked elastin is highly insoluble and extremely stable
Fibrillin
- A large glycoprotein that forms microfibrils
- Provides a scaffold for elastin deposition
- Found in elastic fibers and in elastin-free bundles in the eye, kidney, and tendons
Genetic Defects
- Osteogenesis imperfecta (brittle bones): mutations in collagen genes
- Ehlers-Danlos syndrome: mutations in collagen genes and defects in collagen synthesis
- Scurvy: deficiency of ascorbic acid, leading to reduced collagen synthesis
- Menkes disease: deficiency of copper, leading to defective collagen and elastin cross-linking
Fibronectin and Integrins
- Fibronectin: a glycoprotein that interacts with collagen, proteoglycans, and integrins
- Integrins: transmembrane receptors that interact with fibronectin, collagen, and laminin
- The interaction between fibronectin and integrins is a means of communication between the outside and inside of the cell
Laminin and Basal Lamina
- Laminin: a glycoprotein found in basal lamina, which acts as a supportive tissue
- Laminin anchors the basal lamina to cells by interacting with integrins or dystroglycans
- Laminin is attached to collagen by entactin and perlecan (heparan sulfate proteoglycan)
Proteoglycans
- Glycosaminoglycans (GAGs) covalently linked to a protein core
- Found in all tissues, mainly in the ECM, but some as integral membrane components
- Provide the ground substance of connective tissue, and are associated with each other and with collagen, elastin, and fibronectin
Glycosaminoglycans (GAGs)
- Unbranched polysaccharides made up of repeating disaccharides
- Include hyaluronic acid, chondroitin sulfate, keratan sulfates, heparin, heparan sulfate, and dermatan sulfate
- GAGs are polyanions that bind to cations or polycations, and contribute to the turgor of the tissue
- GAGs form a gel at low concentrations, and act as sieves
Proteoglycan Function
- Influence cell behavior, and act as signaling molecules
- Determine the structural organization of the ECM
- Shedding of proteoglycans is highly regulated, and provides a way for cells to change their surface features quickly### Extracellular Matrix (ECM)
- The ECM consists of fibrous proteins (collagen, elastin, and fibrillin) and adhesion proteins (fibronectin and laminin) and non-fibrous ground substance (proteoglycans)
- ECM composition varies in tissues depending on their functions
- ECM protects organs, provides elasticity, keeps cells and large molecules in place, and provides a porous pathway for nutrient and oxygen diffusion to individual cells
Collagen
- The most abundant fibrous protein (>25% of the proteins in the human body)
- Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
- At least 28 distinct polypeptide chains, encoded by separate genes
- Elongated protein characterized by repetitive amino acid sequence and regular secondary structure
- High degree of tensile strength
α-Chains of Collagen
- Three α-chains, each with ~1000 amino acids, forming a left-handed helix with 3.3 residues per turn
- X and Y can be any amino acids, but X is often proline (~100 residues), and Y is often hydroxyproline (~100 residues)
- 35% glycine, 21% proline and hydroxyproline, 11% alanine; deficient in essential amino acids
- Only glycine at very tight junctions between α-chains
- Pyrrolidone rings permit sharp twisting and confer rigidity
- Hydroxyproline contributes to H-bonding between α-chains
- Hydroxylysine is the site of O-glycosidic linkages
Collagen Triple Helix (Tropocollagen)
- Three α-chains wind around each other in a unique conformation
- Rod-like molecule, 300 nm long, 1.5 nm thick, and MW: 300 kDa
- α-chains are H-bonded between peptide NH (glycine) and peptide CO and between hydroxyproline OH and peptide CO
- Very closely packed left-handed α-chains are wound into a right-handed super helix that resists unwinding
- Superhelical cable, a supramolecular assembly stronger than steel
Matrix Metalloproteinases (MMPs)
- At least 23 different types of human MMPs
- Zn-containing proteases that cleave all ECM proteins
- The propeptide of MMPs contains a cysteine residue that binds to Zn and prevents proteolysis
- Once activated, certain MMPs can activate other MMP forms
Proteoglycans
- Proteins with covalently linked glycosaminoglycans (GAGs)
- Provide the ground substance of connective tissue
- Associated with each other, with collagen, elastin, fibronectin, and laminin
- Found in all tissues, mainly in the ECM, but some as integral membrane components
- At least 30 types of proteoglycans have been characterized
Heparan Sulfate
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A highly sulfated, intracellular form of heparan sulfate produced primarily by mast cells
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Found in liver, lung, and skin
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Has the highest negative charge density of any known biological macromolecule
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Purified heparin is used as a therapeutic agent to inhibit coagulation of blood through its capacity to bind antithrombin### Collagen Synthesis and Structure
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Collagen synthesis occurs intracellularly in fibroblasts, involving pro-α-chains, hydroxylation, and glycosylation.
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Hydroxylation of proline and lysine residues occurs in the endoplasmic reticulum (ER), facilitated by vitamin C.
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Glycosylation of some hydroxylysines occurs in the ER, involving glucosyl and galactosyltransferases.
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The triple helix is formed through self-assembly, with cysteine residues at both terminals assisting in the process.
Collagen Cross-Linking and Fibril Formation
- Extracellular cleavage of N- and C-terminal extension peptides by procollagen N-proteinase and C-proteinase leads to spontaneous assembly of tropocollagen molecules into collagen fibrils.
- Oxidative deamination of ε-amino groups of lysine residues by lysyl oxidase (Cu) forms aldehydes, which then form covalent cross-links.
- The triple helices (collagen molecules) assemble in a quarter-staggered alignment to form fibrils, which are then cross-linked for strength.
Collagen Types and Functions
- Type I collagen is found in skin, bone, and cartilage, while type II collagen is found in cartilage.
- Fibrillar collagens (types I, II, III, V, and XI) form fibrils, while non-fibrillar collagens (types IV, VI, VII, VIII, IX, and X) do not form fibrils.
- Collagen is relatively metabolically stable, with little nutritional value due to its low essential amino acid content.
Disorders of Collagen Biosynthesis
- Osteogenesis imperfecta (brittle bones) is caused by glycine replacement with a larger R group, leading to abnormal pro-chains and fragile bones.
- Ehlers-Danlos syndrome is caused by mutations in collagen genes, resulting in hyperextensibility of the skin, tissue fragility, and joint hypermobility.
- Scurvy is caused by a deficiency of ascorbic acid, impeding post-translational modifications and collagen rigidity.
Elastin
- Elastin is a connective tissue protein responsible for extensibility and elastic recoil.
- Elastin is synthesized as a soluble monomer, tropoelastin, which is cross-linked by lysyl oxidase to form a fibrous mesh.
- Mature elastin is highly insoluble, extremely stable, and has a very low turnover rate.
Fibrillin
- Fibrillins are large glycoproteins that provide a scaffold for elastin deposition.
- Fibrillin microfibrils are found in elastic fibers and elastin-free bundles.
Interactions between Cells and the ECM
- Fibronectin is an adhesive protein that interacts with collagen, proteoglycans, heparin, and fibrin, and helps cells move through the ECM.
- Integrins are transmembrane receptors that interact with collagen, fibronectin, and laminin, and connect to the cytoskeleton.
- The interaction of fibronectin with integrin allows for communication between the outside and inside of the cell.
Basal Lamina
- Laminin is the most abundant protein in the basal lamina, which supports layers of epithelial, muscle, and adipose cells.
- Laminin anchors the basal lamina to cells through integrins and is attached to collagen by entactin and perlecan.
Glycosaminoglycans (GAGs)
- GAGs are unbranched polysaccharides composed of repeating disaccharides, found in the ECM.
- GAGs are huge aggregates that occupy a large volume, contribute to tissue turgor, and act as sieves.
- GAGs are polyanions that bind to cations or polycations, attracting water through osmotic pressure.
Proteoglycans
- Proteoglycans are proteins with covalently linked GAGs, found in the ECM.
- Proteoglycans provide the ground substance of connective tissue, associate with other ECM components, and influence cell behavior.
- At least 30 types of proteoglycans have been characterized, with varying tissue distributions and attached GAGs.
Matrix Metalloproteinases (MMPs)
- MMPs are Zn-containing proteases that cleave all ECM proteins, with at least 23 different types in humans.
- MMP activity is regulated by transcriptional control, proteolytic activation, and inhibition by α2-macroglobulin and TIMPs.
- Coordinated expression of MMPs and TIMPs is required for appropriate growth and cell movement, and dysregulation may contribute to various diseases.
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Description
This quiz covers the composition and functions of the extracellular matrix, including fibrous proteins, adhesion proteins, and nonfibrous ground substance. Learn about its role in protecting organs and providing elasticity in tissues.