Pathways

Compuesto de 3 enzimas (E1, E2 y E3). Su función es realizar la descarboxilación oxidativa del piruvato para formar Acetyl-CoA.

The complement system includes three separate pathways that lead to complement's activation. These pathways all have different molecules that trigger their activation, but all of them lead to a response by phagocytes as part of a response by the innate immune system. In the alternative pathway, complement factor C3 can spontaneously hydrolyze to form a complex with water. Complement factor D is a protease that can work at the same time, and it cleaves complement factor B into factors Ba and Bb. the C3(H2O) complex can bind to factor Bb, which is a C3 convertase, and works to cleave factor C3 into C3a and C3b more quickly. The C3(H2O)Bb complex also binds factor B, leading to easier cleavage into Ba and Bb by factor D. Following this, complement factor C3b can bind to the surface of cells, and on host cells, proteins on the cell membrane can bind to C3b, preventing it from forming complement factor C5 convertase. However, on pathogen cells, these proteins do not exist, complement factor Bb can bind to two molecules of C3b, forming a C5-convertase which is the end point of the other two pathways. In the lectin pathway, mannan-binding lectin serine proteases (MASP) 1 and 2, as well as mannose-binding protein C bind to carbohydrates, specifically mannose, glucose and sugars with specific hydroxide group placements. These sugars are found in the cell walls of bacteria such as salmonella and listeria, as well as some viruses, including HIV-1, and fungal pathogens, such as candida. After the sugar is bound by the proteins, it activates the serine proteases, which then can cleave complement C2 and C4 into C2a, C2b, C4a and C4b respectively. Factors C4b and C2a (sometimes called C2b) can interact to form C3 convertase, which is identical in function to the C3 convertase formed by the alternative pathway, and it works to cleave C3 into C3a and C3b more quickly. Finally for this pathway, a molecule of C3b interacts with the preexisting C3 convertase complex, forming the C5 convertase complex that cleaves factor C5 into C5a and C5b. The final pathway that leads to this point is the classical complement pathway. This pathway is activated by the binding of aggregated antibody-antigen complexes, as well as components of viral and bacterial cells such as lipopolysaccharides, to the C1q protein. C1q is part of the C1 complex, which also includes C1s and C1r. Binding of a substance to C1q causes a conformational change in C1r and C1s, allowing C1s to become an active protease, which then is able to cleave complement factors C2 and C4 into their a and b fragments, as in the lectin pathway. The remainder of the pathway is identical to that of the lectin pathway. Finally, after cleavage of C5 into C5a and C5b by any of the pathways, complement componenets C6, 7, 8 and 9 can interact with component C5b in order to form the membrane attack complex. This complex attaches to the plasma membrane of pathogen cells, forming a hole in the membrane and allowing diffusion of molecules in the cell, and eventually cell death if enough attack complex form.

The complement system includes three separate pathways that lead to complement's activation. These pathways all have different molecules that trigger their activation, but all of them lead to a response by phagocytes as part of a response by the innate immune system. In the alternative pathway, complement factor C3 can spontaneously hydrolyze to form a complex with water. Complement factor D is a protease that can work at the same time, and it cleaves complement factor B into factors Ba and Bb. the C3(H2O) complex can bind to factor Bb, which is a C3 convertase, and works to cleave factor C3 into C3a and C3b more quickly. The C3(H2O)Bb complex also binds factor B, leading to easier cleavage into Ba and Bb by factor D. Following this, complement factor C3b can bind to the surface of cells, and on host cells, proteins on the cell membrane can bind to C3b, preventing it from forming complement factor C5 convertase. However, on pathogen cells, these proteins do not exist, complement factor Bb can bind to two molecules of C3b, forming a C5-convertase which is the end point of the other two pathways. In the lectin pathway, mannan-binding lectin serine proteases (MASP) 1 and 2, as well as mannose-binding protein C bind to carbohydrates, specifically mannose, glucose and sugars with specific hydroxide group placements. These sugars are found in the cell walls of bacteria such as salmonella and listeria, as well as some viruses, including HIV-1, and fungal pathogens, such as candida. After the sugar is bound by the proteins, it activates the serine proteases, which then can cleave complement C2 and C4 into C2a, C2b, C4a and C4b respectively. Factors C4b and C2a (sometimes called C2b) can interact to form C3 convertase, which is identical in function to the C3 convertase formed by the alternative pathway, and it works to cleave C3 into C3a and C3b more quickly. Finally for this pathway, a molecule of C3b interacts with the preexisting C3 convertase complex, forming the C5 convertase complex that cleaves factor C5 into C5a and C5b. The final pathway that leads to this point is the classical complement pathway. This pathway is activated by the binding of aggregated antibody-antigen complexes, as well as components of viral and bacterial cells such as lipopolysaccharides, to the C1q protein. C1q is part of the C1 complex, which also includes C1s and C1r. Binding of a substance to C1q causes a conformational change in C1r and C1s, allowing C1s to become an active protease, which then is able to cleave complement factors C2 and C4 into their a and b fragments, as in the lectin pathway. The remainder of the pathway is identical to that of the lectin pathway. Finally, after cleavage of C5 into C5a and C5b by any of the pathways, complement componenets C6, 7, 8 and 9 can interact with component C5b in order to form the membrane attack complex. This complex attaches to the plasma membrane of pathogen cells, forming a hole in the membrane and allowing diffusion of molecules in the cell, and eventually cell death if enough attack complex form.

The complement system includes three separate pathways that lead to complement's activation. These pathways all have different molecules that trigger their activation, but all of them lead to a response by phagocytes as part of a response by the innate immune system. In the alternative pathway, complement factor C3 can spontaneously hydrolyze to form a complex with water. Complement factor D is a protease that can work at the same time, and it cleaves complement factor B into factors Ba and Bb. the C3(H2O) complex can bind to factor Bb, which is a C3 convertase, and works to cleave factor C3 into C3a and C3b more quickly. The C3(H2O)Bb complex also binds factor B, leading to easier cleavage into Ba and Bb by factor D. Following this, complement factor C3b can bind to the surface of cells, and on host cells, proteins on the cell membrane can bind to C3b, preventing it from forming complement factor C5 convertase. However, on pathogen cells, these proteins do not exist, complement factor Bb can bind to two molecules of C3b, forming a C5-convertase which is the end point of the other two pathways. In the lectin pathway, mannan-binding lectin serine proteases (MASP) 1 and 2, as well as mannose-binding protein C bind to carbohydrates, specifically mannose, glucose and sugars with specific hydroxide group placements. These sugars are found in the cell walls of bacteria such as salmonella and listeria, as well as some viruses, including HIV-1, and fungal pathogens, such as candida. After the sugar is bound by the proteins, it activates the serine proteases, which then can cleave complement C2 and C4 into C2a, C2b, C4a and C4b respectively. Factors C4b and C2a (sometimes called C2b) can interact to form C3 convertase, which is identical in function to the C3 convertase formed by the alternative pathway, and it works to cleave C3 into C3a and C3b more quickly. Finally for this pathway, a molecule of C3b interacts with the preexisting C3 convertase complex, forming the C5 convertase complex that cleaves factor C5 into C5a and C5b. The final pathway that leads to this point is the classical complement pathway. This pathway is activated by the binding of aggregated antibody-antigen complexes, as well as components of viral and bacterial cells such as lipopolysaccharides, to the C1q protein. C1q is part of the C1 complex, which also includes C1s and C1r. Binding of a substance to C1q causes a conformational change in C1r and C1s, allowing C1s to become an active protease, which then is able to cleave complement factors C2 and C4 into their a and b fragments, as in the lectin pathway. The remainder of the pathway is identical to that of the lectin pathway. Finally, after cleavage of C5 into C5a and C5b by any of the pathways, complement componenets C6, 7, 8 and 9 can interact with component C5b in order to form the membrane attack complex. This complex attaches to the plasma membrane of pathogen cells, forming a hole in the membrane and allowing diffusion of molecules in the cell, and eventually cell death if enough attack complex form.

The complement system includes three separate pathways that lead to complement's activation. These pathways all have different molecules that trigger their activation, but all of them lead to a response by phagocytes as part of a response by the innate immune system. In the alternative pathway, complement factor C3 can spontaneously hydrolyze to form a complex with water. Complement factor D is a protease that can work at the same time, and it cleaves complement factor B into factors Ba and Bb. the C3(H2O) complex can bind to factor Bb, which is a C3 convertase, and works to cleave factor C3 into C3a and C3b more quickly. The C3(H2O)Bb complex also binds factor B, leading to easier cleavage into Ba and Bb by factor D. Following this, complement factor C3b can bind to the surface of cells, and on host cells, proteins on the cell membrane can bind to C3b, preventing it from forming complement factor C5 convertase. However, on pathogen cells, these proteins do not exist, complement factor Bb can bind to two molecules of C3b, forming a C5-convertase which is the end point of the other two pathways. In the lectin pathway, mannan-binding lectin serine proteases (MASP) 1 and 2, as well as mannose-binding protein C bind to carbohydrates, specifically mannose, glucose and sugars with specific hydroxide group placements. These sugars are found in the cell walls of bacteria such as salmonella and listeria, as well as some viruses, including HIV-1, and fungal pathogens, such as candida. After the sugar is bound by the proteins, it activates the serine proteases, which then can cleave complement C2 and C4 into C2a, C2b, C4a and C4b respectively. Factors C4b and C2a (sometimes called C2b) can interact to form C3 convertase, which is identical in function to the C3 convertase formed by the alternative pathway, and it works to cleave C3 into C3a and C3b more quickly. Finally for this pathway, a molecule of C3b interacts with the preexisting C3 convertase complex, forming the C5 convertase complex that cleaves factor C5 into C5a and C5b. The final pathway that leads to this point is the classical complement pathway. This pathway is activated by the binding of aggregated antibody-antigen complexes, as well as components of viral and bacterial cells such as lipopolysaccharides, to the C1q protein. C1q is part of the C1 complex, which also includes C1s and C1r. Binding of a substance to C1q causes a conformational change in C1r and C1s, allowing C1s to become an active protease, which then is able to cleave complement factors C2 and C4 into their a and b fragments, as in the lectin pathway. The remainder of the pathway is identical to that of the lectin pathway. Finally, after cleavage of C5 into C5a and C5b by any of the pathways, complement componenets C6, 7, 8 and 9 can interact with component C5b in order to form the membrane attack complex. This complex attaches to the plasma membrane of pathogen cells, forming a hole in the membrane and allowing diffusion of molecules in the cell, and eventually cell death if enough attack complex form.

Congenital Bile Acid Synthesis Defect Type II is a congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency is caused by mutation in the AKR1D1 gene. 3-oxo-5-beta-steroid 4-dehydrogenase catalyzes the bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one. Chenodeoxycholic acid and cholic acid are decreased in plasma and urine. Symptoms of this disease include cholestatic jaundice, atypical oxo and allo bile acids in urine and serum, liver failure, and steatosis.

Congenital Bile Acid Synthesis Defect Type II is a congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency is caused by mutation in the AKR1D1 gene. 3-oxo-5-beta-steroid 4-dehydrogenase catalyzes the bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one. Chenodeoxycholic acid and cholic acid are decreased in plasma and urine. Symptoms of this disease include cholestatic jaundice, atypical oxo and allo bile acids in urine and serum, liver failure, and steatosis.

Congenital Bile Acid Synthesis Defect Type II is a congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency is caused by mutation in the AKR1D1 gene. 3-oxo-5-beta-steroid 4-dehydrogenase catalyzes the bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one. Chenodeoxycholic acid and cholic acid are decreased in plasma and urine. Symptoms of this disease include cholestatic jaundice, atypical oxo and allo bile acids in urine and serum, liver failure, and steatosis.