El documento proporciona una introducción al metabolismo, describiendo las rutas metabólicas como lineales, circulares o en espiral. Explica que el metabolismo celular incluye los procesos catabólicos de utilización de energía y los anabólicos de síntesis, y que está regulado por la concentración de enzimas, sustratos y modificaciones. También distingue entre autotrófos y heterotrófos, y describe brevemente la glucólisis y la respiración aerobia.
Exposición acerca del metabolismo de fármacos en el organismo humana, se presenta interacción a nivel enzimático, asi como explicaciones sobre el ciclo enterohepático, y el efecto del primer paso.
Exposición acerca del metabolismo de fármacos en el organismo humana, se presenta interacción a nivel enzimático, asi como explicaciones sobre el ciclo enterohepático, y el efecto del primer paso.
Los seres humanos estamos expuestos todos los dias a diversas cantidades de compuestos, los cuales son absorbidos por nuestro organismo de diferentes maneras conllevando a someterse a un proceso de metabolización.
Los fármacos pasan por un proceso similar al ser absorbidos o administrados en nuestro cuerpo.
1891 - 14 de Julio - Rohrmann recibió una patente alemana (n° 64.209) para s...Champs Elysee Roldan
El concepto del cohete como plataforma de instrumentación científica de gran altitud tuvo sus precursores inmediatos en el trabajo de un francés y dos Alemanes a finales del siglo XIX.
Ludewig Rohrmann de Drauschwitz Alemania, concibió el cohete como un medio para tomar fotografías desde gran altura. Recibió una patente alemana para su aparato (n° 64.209) el 14 de julio de 1891.
En vista de la complejidad de su aparato fotográfico, es poco probable que su dispositivo haya llegado a desarrollarse con éxito. La cámara debía haber sido accionada por un mecanismo de reloj que accionaría el obturador y también posicionaría y retiraría los porta películas. También debía haber sido suspendido de un paracaídas en una articulación universal. Tanto el paracaídas como la cámara debían ser recuperados mediante un cable atado a ellos y desenganchado de un cabrestante durante el vuelo del cohete. Es difícil imaginar cómo un mecanismo así habría resistido las fuerzas del lanzamiento y la apertura del paracaídas.
10. El metabolismo o flujo metabólico es regulado por:
•concentración de la enzimas
•concentración del sustrato
•modulaciones alostéricas
•modificaciones covalentes
Retroalimentación negativa
Feedback inhibition or Negative feedback
39. Aerobic RespirationAerobic Respiration
Bacterias andBacterias and
EukaryotsEukaryots
Glycolysis occurs in theGlycolysis occurs in the cytosolcytosol
All other stages in theAll other stages in the mitochondriamitochondria
50. En el hígado las hexocinasas I, II y III son inhibida
alostéricamente por glucosa 6-P
Glucocinasa en hígado (hexocinasa IV)
no es inhibida por glucosa 6-P
*
71. En el hígado las hexocinasas
I, II y III son inhibida
alostéricamente por glucosa 6-P
Glucocinasa en hígado
(hexocinasa IV)
no es inhibida por glucosa 6-P
Es inhibida por fructosa 6-P y
una proteína reguladora.
incubated with glucagon,
pyruvate kinase is
phosphorylated
Figure 10.1
Anabolism and catabolism. Anabolic reactions use small molecules and chemical energy in the synthesis of organic molecules and in the performance of cellular work. Solar energy is an important source of metabolic energy in photosynthetic bacteria and plants. Some molecules, including those obtained from food, are catabolized to release energy and either monomeric building blocks or waste products. In the remaining figures in this chapter, blue arrows represent biosynthesis pathways and red arrows represent catabolism pathways.
Figure 10.2
Forms of metabolic pathways. (a) The biosynthesis of serine is an example of a linear metabolic pathway. The product of each step is the substrate for the next step. (b) The sequence of reactions in a cyclic pathway forms a closed loop. In the citric acid cycle, an acetyl group is metabolized via reactions that regenerate the intermediates of the cycle. (c) In fatty acid biosynthesis, a spiral pathway, the same set of enzymes catalyzes a progressive lengthening of the acyl chain.
Figure 10.2
Forms of metabolic pathways. (a) The biosynthesis of serine is an example of a linear metabolic pathway. The product of each step is the substrate for the next step. (b) The sequence of reactions in a cyclic pathway forms a closed loop. In the citric acid cycle, an acetyl group is metabolized via reactions that regenerate the intermediates of the cycle. (c) In fatty acid biosynthesis, a spiral pathway, the same set of enzymes catalyzes a progressive lengthening of the acyl chain.
Figure 10.2
Forms of metabolic pathways. (a) The biosynthesis of serine is an example of a linear metabolic pathway. The product of each step is the substrate for the next step. (b) The sequence of reactions in a cyclic pathway forms a closed loop. In the citric acid cycle, an acetyl group is metabolized via reactions that regenerate the intermediates of the cycle. (c) In fatty acid biosynthesis, a spiral pathway, the same set of enzymes catalyzes a progressive lengthening of the acyl chain.
Figure 10.6
Overview of catabolic pathways. Amino acids, nucleotides, monosaccharides, and fatty acids are formed by enzymatic hydrolysis of their respective polymers. They are then degraded in oxidative reactions and energy is conserved in ATP and reduced coenzymes (mostly NADH). (Numbers in parentheses refer to the chapters and section in this book.)
Figure 10.5
Overview of anabolic pathways. Large molecules are synthesized from smaller ones by adding carbon (usually derived from CO2) and nitrogen (usually as NH3+). The main pathways include the citric acid cycle, which supplies the intermediates in amino acid biosynthesis, and gluconeogenesis, which results in the production of glucose. The energy for biosynthetic pathways is supplied by light in photosynthetic organisms or by the breakdown of inorganic molecules in other autotrophs. (Numbers in parentheses refer to the chapters and section in this book.)
Figure 10.3
Single-step versus multistep pathways. (a) The synthesis of glucose cannot be accomplished in a single step. Multistep biosynthesis is coupled to the input of small quanta of energy from ATP and NADH. (b) The uncontrolled combustion of glucose releases a large amount of energy all at once. A multistep enzyme catalyzed pathway releases the same amount of energy but conserves much of it in a manageable form.
Figure 10.4
Regulatory role of a protein kinase. The effect of the initial signal is amplified by the signaling cascade. Phosphorylation of different cellular proteins by the activated kinase results in coordinated regulation of different metabolic pathways. Some pathways may be activated, whereas others are inhibited. —P represents a protein-bound phosphate group.
Figure 10.6
Overview of catabolic pathways. Amino acids, nucleotides, monosaccharides, and fatty acids are formed by enzymatic hydrolysis of their respective polymers. They are then degraded in oxidative reactions and energy is conserved in ATP and reduced coenzymes (mostly NADH). (Numbers in parentheses refer to the chapters and section in this book.)
Figure 10.5
Overview of anabolic pathways. Large molecules are synthesized from smaller ones by adding carbon (usually derived from CO2) and nitrogen (usually as NH3+). The main pathways include the citric acid cycle, which supplies the intermediates in amino acid biosynthesis, and gluconeogenesis, which results in the production of glucose. The energy for biosynthetic pathways is supplied by light in photosynthetic organisms or by the breakdown of inorganic molecules in other autotrophs. (Numbers in parentheses refer to the chapters and section in this book.)
Figure 10.9
Hydrolysis of ATP to (1) ADP and inorganic phosphate (Pi) and (2) AMP and inorganic pyrophosphate (PPi).
Figure 10.11
Relative phosphoryl group–transfer potentials. A compound with a high group–transfer potential (i.e., a large negative value of G°hydrolysis) can donate its phosphoryl group to a compound that is less energy-rich. The reaction arrows indicate the predominant direction of phosphoryl-group transfer under standard conditions.
Figure 11.1
Gluconeogenesis, glycolysis, and the citric acid cycle. Glucose is synthesized from pyruvate via oxaloacetate and phosphoenolpyruvate. In glycolysis, glucose is degraded to pyruvate. Many (but not all) of the steps in glycolysis are the reverse of the gluconeogenesis reactions. The acetyl group of pyruvate is transferred to coenzyme A (CoA) and oxidized to carbon dioxide by the citric acid cycle. Energy in the form of ATP equivalents is required for the synthesis of glucose. Some of this energy is recovered in glycolysis but much more is recovered as a result of the citric acid cycle.
Figure 10.9
Hydrolysis of ATP to (1) ADP and inorganic phosphate (Pi) and (2) AMP and inorganic pyrophosphate (PPi).
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.4
Conversion of glucose 6-phosphate to fructose 6-phosphate. This aldose–ketose isomerization is catalyzed by glucose-6-phosphate isomerase.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.6
Fate of carbon atoms from the hexose stage to the triose stage of glycolysis. All numbers refer to the carbon atoms in the original glucose molecule.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Formation of 2,3-bisphosphoglycerate (2,3BPG) in red blood cells.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 11.2
Conversion of glucose to pyruvate by glycolysis. At Step 4, the hexose molecule is split in two, and the remaining reactions of glycolysis are traversed by two triose molecules. ATP is consumed in the hexose stage and generated in the triose stage.
Figure 10.9
Hydrolysis of ATP to (1) ADP and inorganic phosphate (Pi) and (2) AMP and inorganic pyrophosphate (PPi).
Figure 11.9
Four major fates of pyruvate: (a) Under aerobic conditions, pyruvate is oxidized to the acetyl group of acetyl CoA, which can enter the citric acid cycle for further oxidation. (b) Pyruvate can be converted to oxaloacetate, which can be a precursor in gluconeogenesis. (c) Under anaerobic conditions certain microorganisms ferment glucose to ethanol via pyruvate. (d) Glucose undergoes anaerobic glycolysis to lactate in vigorously exercising muscles, red blood cells, and certain other cells. Pyruvate also enters anabolic pathways that are not shown here.
Figure 11.13
Regulation of glucose transport by insulin. The binding of insulin to cell-surface receptors stimulates intracellular vesicles containing membrane-embedded GLUT4 transporters to fuse with the plasma membrane. This delivers GLUT4 transporters to the cell surface and thereby increases the capacity of the cell to transport glucose.
Glucose 6-phosphate is at a pivotal position in carbohydrate metabolism in the liver.
Figure 11.12
Summary of the metabolic regulation of the glycolytic pathway in mammals. Not shown are the effects of ADP on PFK-1, which vary among species.
Figure 11.14
Plot of initial velocity (v0) versus glucose concentration for glucokinase. The addition of a regulatory protein lowers the enzyme’s affinity for glucose. The blood glucose concentration is 5 to 10 mM.
Figure 11.15
Regulation of PFK-1 by ATP and AMP. In the absence of AMP, PFK-1 is almost completely inhibited by physiological concentrations of ATP. In the range of AMP concentrations found in the cell, the inhibition of PFK-1 by ATP is almost completely relieved. [Adapted from Martin, B. R. (1987). Metabolic Regulation: A Molecular Approach (Oxford: Blackwell Scientific Publications), p. 222.]
Figure 11.16
Interconversion of -D-fructose 6-phosphate and -D-fructose 2,6-bisphosphate.
Figure 11.17
Effect of glucagon on glycolysis in the liver. The hormone glucagon is released from the pancreas into the blood when blood glucose levels are low. When glucagon binds to its receptor, protein kinase A is activated by cyclic AMP via the adenylyl cyclase signaling pathway. The protein kinase catalyzes phosphorylation of the bifunctional enzyme PFK-2, inhibiting its kinase activity and stimulating its fructose 2,6-bisphosphatase activity. When the concentration of glucagon is high, the formation of the potent PFK-1 activator fructose 2,6-bisphosphate is decreased and its degradation is increased. As a result, the major pathway—glycolysis—slows, using less glucose. Glucagon also signals the liver to increase both the synthesis of glucose and the mobilization of glucose from glycogen.
Figure 11.18
Plots of initial velocity (v0) versus phosphoenolpyruvate concentration for pyruvate kinase. (a) For isozymes in some cells, the presence of fructose 1,6-bisphosphate shifts the curve to the left, indicating that fructose 1,6-bisphosphate is an activator of the enzymes. (b) When liver or intestinal cells are incubated with glucagon, pyruvate kinase is phosphorylated by the action of protein kinase A. The curve shifts to the right, indicating less activity for pyruvate kinase.
Figure 11.18
Plots of initial velocity (v0) versus phosphoenolpyruvate concentration for pyruvate kinase. (a) For isozymes in some cells, the presence of fructose 1,6-bisphosphate shifts the curve to the left, indicating that fructose 1,6-bisphosphate is an activator of the enzymes. (b) When liver or intestinal cells are incubated with glucagon, pyruvate kinase is phosphorylated by the action of protein kinase A. The curve shifts to the right, indicating less activity for pyruvate kinase.
