1. Glycolysis is a pathway that takes place in the cytosol of cells and involves the breakdown of glucose to pyruvate. It involves 10 enzyme-catalyzed steps and results in the production of ATP.
2. The first three steps involve phosphorylation of glucose to glucose-6-phosphate by hexokinase, isomerization to fructose-6-phosphate by phosphoglucose isomerase, and phosphorylation to fructose-1,6-bisphosphate by phosphofructokinase.
3. Subsequent steps break down the six-carbon glucose into two three-carbon molecules, convert them to pyruvate, and generate ATP through substrate-level phosphorylation
1. Glycolysis is the pathway where glucose is broken down to pyruvate with production of ATP. It takes place in the cytosol of cells.
2. Key steps include phosphorylation of glucose to glucose-6-phosphate by hexokinase, isomerization to fructose-6-phosphate, phosphorylation of fructose to fructose-1,6-bisphosphate, cleavage to two 3-carbon molecules, conversion of one to glyceraldehyde-3-phosphate and isomerization, oxidation and phosphorylation to 1,3-bisphosphoglycerate, substrate-level phosphorylation to form ATP, and generation of pyruvate from phosphoenolpyruvate.
Glycolysis is the pathway where glucose is oxidized to pyruvate, producing energy in the form of ATP and NADH. It takes place in the cytosol of cells and involves 10 enzyme-catalyzed reactions. Glucose is first phosphorylated to glucose-6-phosphate by hexokinase using ATP as an energy source. A series of reactions then convert it into two molecules of pyruvate, producing a net yield of two ATP and two NADH per glucose molecule. The fate of pyruvate is determined by whether the cell has oxygen present.
Glycolysis is a catabolic pathway that breaks down glucose to extract energy. It occurs in 10 steps and involves 2 phases. In the first phase, energy is invested to phosphorylate and cleave glucose. In the second phase, the products are further broken down with a net generation of ATP. Glycolysis converts one glucose into two pyruvate molecules, produces 2 NADH, uses 2 ATP and generates a net of 2 ATP per glucose. This pathway is regulated by controlling the activity of three key enzymes: hexokinase, phosphofructokinase, and pyruvate kinase.
Glycolysis is a catabolic pathway that breaks down glucose to extract energy through the release of ATP. It occurs in 10 steps involving 9 enzymes. The first 5 steps are a preparatory phase requiring 2 ATP but generating intermediates. The last 5 steps generate 4 ATP and 2 NADH from the intermediates, resulting in a net gain of 2 ATP per glucose. Three key regulating enzymes are hexokinase, phosphofructokinase, and pyruvate kinase which control the rate of glycolysis in response to cellular energy levels.
The document summarizes the process of glycolysis. It begins with glucose being phosphorylated to glucose-6-phosphate by hexokinase. Glucose-6-phosphate then undergoes isomerization and a series of phosphorylation and dephosphorylation reactions to yield two molecules of pyruvate. Energy from glucose is initially stored as ATP and later released. Key steps include phosphofructokinase regulating flux and glyceraldehyde-3-phosphate dehydrogenase generating NADH.
The pentose phosphate pathway generates NADPH and pentose sugars. Glucose-6-phosphate enters the pathway and is oxidized by glucose-6-phosphate dehydrogenase, producing 6-phosphogluconolactone. This is hydrolyzed to 6-phosphogluconate by 6-phosphogluconolactonase. 6-Phosphogluconate dehydrogenase further oxidizes this to ribulose-5-phosphate, producing NADPH. Ribulose-5-phosphate can be converted to other 5-carbon sugars like ribose-5-phosphate. Transketolase and transaldolase reactions interconvert pentose and triose phosphates to regenerate ribulose
The pentose phosphate pathway generates NADPH and pentose sugars. It has both an oxidative and non-oxidative phase. In the oxidative phase, glucose-6-phosphate is oxidized to produce NADPH. In the non-oxidative phase, 5-carbon sugars are converted into 3 and 6 carbon sugars through a series of isomerization, epimerization, and transketolase reactions. The pathway is important as it provides NADPH for biosynthetic reactions and pentose sugars for nucleotide synthesis. A defect in glucose-6-phosphate dehydrogenase can lead to insufficient NADPH and glutathione, resulting in hemolytic anemia due to oxidative damage of red blood cells.
1. Glycolysis is the pathway where glucose is broken down to pyruvate with production of ATP. It takes place in the cytosol of cells.
2. Key steps include phosphorylation of glucose to glucose-6-phosphate by hexokinase, isomerization to fructose-6-phosphate, phosphorylation of fructose to fructose-1,6-bisphosphate, cleavage to two 3-carbon molecules, conversion of one to glyceraldehyde-3-phosphate and isomerization, oxidation and phosphorylation to 1,3-bisphosphoglycerate, substrate-level phosphorylation to form ATP, and generation of pyruvate from phosphoenolpyruvate.
Glycolysis is the pathway where glucose is oxidized to pyruvate, producing energy in the form of ATP and NADH. It takes place in the cytosol of cells and involves 10 enzyme-catalyzed reactions. Glucose is first phosphorylated to glucose-6-phosphate by hexokinase using ATP as an energy source. A series of reactions then convert it into two molecules of pyruvate, producing a net yield of two ATP and two NADH per glucose molecule. The fate of pyruvate is determined by whether the cell has oxygen present.
Glycolysis is a catabolic pathway that breaks down glucose to extract energy. It occurs in 10 steps and involves 2 phases. In the first phase, energy is invested to phosphorylate and cleave glucose. In the second phase, the products are further broken down with a net generation of ATP. Glycolysis converts one glucose into two pyruvate molecules, produces 2 NADH, uses 2 ATP and generates a net of 2 ATP per glucose. This pathway is regulated by controlling the activity of three key enzymes: hexokinase, phosphofructokinase, and pyruvate kinase.
Glycolysis is a catabolic pathway that breaks down glucose to extract energy through the release of ATP. It occurs in 10 steps involving 9 enzymes. The first 5 steps are a preparatory phase requiring 2 ATP but generating intermediates. The last 5 steps generate 4 ATP and 2 NADH from the intermediates, resulting in a net gain of 2 ATP per glucose. Three key regulating enzymes are hexokinase, phosphofructokinase, and pyruvate kinase which control the rate of glycolysis in response to cellular energy levels.
The document summarizes the process of glycolysis. It begins with glucose being phosphorylated to glucose-6-phosphate by hexokinase. Glucose-6-phosphate then undergoes isomerization and a series of phosphorylation and dephosphorylation reactions to yield two molecules of pyruvate. Energy from glucose is initially stored as ATP and later released. Key steps include phosphofructokinase regulating flux and glyceraldehyde-3-phosphate dehydrogenase generating NADH.
The pentose phosphate pathway generates NADPH and pentose sugars. Glucose-6-phosphate enters the pathway and is oxidized by glucose-6-phosphate dehydrogenase, producing 6-phosphogluconolactone. This is hydrolyzed to 6-phosphogluconate by 6-phosphogluconolactonase. 6-Phosphogluconate dehydrogenase further oxidizes this to ribulose-5-phosphate, producing NADPH. Ribulose-5-phosphate can be converted to other 5-carbon sugars like ribose-5-phosphate. Transketolase and transaldolase reactions interconvert pentose and triose phosphates to regenerate ribulose
The pentose phosphate pathway generates NADPH and pentose sugars. It has both an oxidative and non-oxidative phase. In the oxidative phase, glucose-6-phosphate is oxidized to produce NADPH. In the non-oxidative phase, 5-carbon sugars are converted into 3 and 6 carbon sugars through a series of isomerization, epimerization, and transketolase reactions. The pathway is important as it provides NADPH for biosynthetic reactions and pentose sugars for nucleotide synthesis. A defect in glucose-6-phosphate dehydrogenase can lead to insufficient NADPH and glutathione, resulting in hemolytic anemia due to oxidative damage of red blood cells.
This document discusses carbohydrate metabolism and glycolysis. It begins by classifying carbohydrate metabolism into glycolysis, the Krebs cycle, the hexose monophosphate shunt, glycogenesis, glycogenolysis, and gluconeogenesis. It then provides details on glycolysis, including that it converts glucose to pyruvate or lactate, involving 10 reactions in 3 stages. Key enzymes and reactions in each stage are described. The document also discusses regulation of glycolysis and differences between hexokinase and glucokinase.
Glycolysis is a ten step pathway that converts glucose into pyruvate, generating ATP and NADH. It occurs in the cytosol of cells and consists of two phases: the first phase converts glucose to two molecules of glyceraldehyde-3-phosphate (G3P) and the second phase converts G3P to two pyruvates while producing ATP and NADH. Glycolysis generates two ATP per glucose during substrate-level phosphorylation. In aerobic conditions, pyruvate enters the citric acid cycle and NADH is oxidized through oxidative phosphorylation to generate additional ATP. In anaerobic conditions, NADH is regenerated by converting pyruvate to lactate through fermentation
This is the glycolysis component of Bioc (chem) 361 at UAE University. Some from Campbell 6th ed and the rest from General, Organic, and Biochemistry, 5th edition (2007), by K.J.Denniston, J.J.Topping, and R.L.Caret.
1) The Calvin cycle fixes carbon from carbon dioxide into organic molecules like glucose. It uses energy from light reactions to convert CO2 into glyceraldehyde-3-phosphate in chloroplasts.
2) The key enzyme is RuBisCO, which catalyzes the carboxylation of ribulose-1,5-bisphosphate with CO2 to form two molecules of 3-phosphoglycerate. These are then reduced and regenerated into more ribulose-1,5-bisphosphate in a cyclic process.
3) The cycle requires ATP and NADPH from light reactions. It is regulated by light and dark conditions that affect enzyme activation and pH levels in the chloroplast.
Digestion of glycolysis --Sir Khalid (Biochem)Soft-Learners
The document discusses digestion and absorption of carbohydrates. Carbohydrates taken in through the diet are broken down through digestion in the mouth, stomach, and small intestine by enzymes. Absorption occurs primarily in the small intestine. Glycolysis is then discussed, which is the breakdown of glucose within cells to extract energy. Glycolysis occurs in 10 steps involving multiple enzymes and produces pyruvate, ATP, and NADH.
The document discusses digestion and absorption of carbohydrates. Carbohydrates taken in through the diet are broken down through digestion in the mouth, stomach, and small intestine by enzymes. Absorption occurs primarily in the small intestine. Glycolysis is then discussed, which is the breakdown of glucose within cells to extract energy. Glycolysis occurs in 10 steps involving multiple enzymes and produces pyruvate, ATP, and NADH. Pyruvate can then be further broken down to lactate or enter the citric acid cycle.
Complete Set of Metabolism of Carbohydrate in that second chapter, glycolysis.
This presentation covers complete glycolysis pathway with step wise animated reactions and it includes clinical aspects also. This presentation is good for MBBS students.
Glycolysis is the pathway by which cells break down glucose to extract energy. Glucose first undergoes phosphorylation by hexokinase to form glucose-6-phosphate. A series of enzymatic reactions then convert glucose-6-phosphate through intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate, extracting energy in the form of ATP. Key steps include substrate-level phosphorylation by phosphofructokinase-1 and oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, reducing NAD+ to NADH. The pathway ultimately forms two pyruvate molecules from each glucose.
The document summarizes several metabolic pathways including:
1) The pentose phosphate pathway which generates NADPH and ribose-5-phosphate in the oxidative phase and converts intermediates to glycolysis in the nonoxidative phase.
2) Fructose metabolism which occurs mainly in the liver and bypasses regulation of glycolysis.
3) Galactose metabolism which is converted to glucose-1-phosphate in the liver.
Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors in the liver and kidneys. It occurs mainly in the liver and helps prevent hypoglycemia during fasting. While some of the same enzymes are used in both gluconeogenesis and glycolysis, three irreversible glycolysis reactions must be bypassed. The document provides details on the enzymes and reactions involved in bypassing these steps, including pyruvate carboxylase and PEP carboxykinase. Regulation ensures that gluconeogenesis and glycolysis do not operate simultaneously to avoid an energy-wasting cycle.
Glucose-6-phosphate acts as a branch point for several metabolic pathways. It can be used for glycolysis, glycogen synthesis, the hexose monophosphate shunt, and gluconeogenesis. The hexose monophosphate shunt generates NADPH for biosynthetic reactions through glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. NADPH is required for processes like fatty acid synthesis, cholesterol synthesis, and maintaining reduced glutathione levels in red blood cells. Glucose-6-phosphate dehydrogenase deficiency, which reduces NADPH production, provides some protection against malaria by shortening red blood cell lifespan.
1. The Calvin cycle fixes carbon dioxide into carbohydrates using energy from light reactions that produce ATP and NADPH.
2. Enzymes of the Calvin cycle regenerate the 5-carbon sugar RuBP from 3-carbon glyceraldehyde-3-P in chloroplasts.
3. Overall, 3 molecules of CO2 are fixed into one molecule each of two 3-carbon glyceraldehyde-3-P, with the remaining carbons recycled to regenerate 3 molecules of RuBP to continue the cycle.
This document summarizes glycolysis, the metabolic pathway that converts glucose into pyruvate. It describes the two phases of glycolysis - the preparatory phase which requires ATP, and the payoff phase which yields ATP and NADH. It also lists the three possible fates of the pyruvate produced: lactic acid fermentation, ethanol fermentation, or further processing in the citric acid cycle.
1. Glycolysis takes place in the cytosol and involves the conversion of glucose to glucose-6-phosphate through a reaction catalyzed by hexokinase using ATP as an energy source.
2. Glucose-6-phosphate then undergoes a series of reactions catalyzed by different enzymes to produce two molecules of pyruvate, involving phosphorylation, isomerization, and cleavage reactions.
3. These reactions initially require energy input in the form of ATP but later reactions produce ATP and NADH, which are used in downstream metabolic pathways.
The document discusses the hexose monophosphate shunt (HMP shunt), an alternative pathway to glycolysis and the TCA cycle for oxidizing glucose. The HMP shunt occurs in the cytosol and is more anabolic in nature, producing NADPH and pentose through oxidative and non-oxidative phases. Tissues with high HMP shunt activity like the liver, adipose tissue, and lactating mammary glands use the NADPH produced for biosynthesis of fatty acids and steroids.
Gluconeogenesis and glycolysis share many of the same enzymes but operate in opposite directions. Three irreversible steps in glycolysis - those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase - must be bypassed in gluconeogenesis. This is accomplished through different enzymes that catalyze reversible reactions, such as glucose-6-phosphatase and fructose-1,6-bisphosphatase. Regulation ensures that glycolysis and gluconeogenesis do not operate simultaneously, which would waste energy. Key control points include allosteric regulation by adenine nucleotides and hormonal stimulation of cAMP and protein phosphorylation.
1) The document summarizes key steps in glycolysis, beginning with the breakdown of glucose and ending with the production of pyruvate.
2) Glucose is phosphorylated by hexokinase to produce glucose-6-phosphate, then isomerized to fructose-6-phosphate and phosphorylated again to produce fructose-1,6-bisphosphate.
3) Fructose-1,6-bisphosphate is cleaved by aldolase into two trioses - glyceraldehyde-3-phosphate and dihydroxyacetone phosphate - with the release of energy in the form of ATP.
1) Dr. Khalid Alsharafa studies plant stress physiology, including how plants sense and respond to stresses like high light, temperature extremes, heavy metals, salinity, drought, and pathogens.
2) Plants have developed strategies to respond to stress, such as lowering reactive oxygen species production, scavenging ROS through antioxidants and enzymes, and signal transduction pathways that trigger stress responses.
3) Dr. Alsharafa's research aims to analyze post-transcriptional regulation of enzyme activity under abiotic stress of different durations and intensities, monitor plant acclimation to biotic and abiotic stresses over time, and detect retrograde signaling in response to abiotic stress.
Somatic hybridization involves fusing plant cell protoplasts (naked plant cells without cell walls) from two different plant species or varieties. This is done through isolating protoplasts enzymatically, fusing them using chemicals or electricity, selecting hybrid cells, culturing the hybrid cells, and regenerating hybrid plants. Somatic hybridization allows for the transfer of useful traits like disease resistance between sexually incompatible plant species. It has been used to create novel crop hybrids and backcross fertile somatic hybrids in plants like citrus and potatoes.
This document discusses carbohydrate metabolism and glycolysis. It begins by classifying carbohydrate metabolism into glycolysis, the Krebs cycle, the hexose monophosphate shunt, glycogenesis, glycogenolysis, and gluconeogenesis. It then provides details on glycolysis, including that it converts glucose to pyruvate or lactate, involving 10 reactions in 3 stages. Key enzymes and reactions in each stage are described. The document also discusses regulation of glycolysis and differences between hexokinase and glucokinase.
Glycolysis is a ten step pathway that converts glucose into pyruvate, generating ATP and NADH. It occurs in the cytosol of cells and consists of two phases: the first phase converts glucose to two molecules of glyceraldehyde-3-phosphate (G3P) and the second phase converts G3P to two pyruvates while producing ATP and NADH. Glycolysis generates two ATP per glucose during substrate-level phosphorylation. In aerobic conditions, pyruvate enters the citric acid cycle and NADH is oxidized through oxidative phosphorylation to generate additional ATP. In anaerobic conditions, NADH is regenerated by converting pyruvate to lactate through fermentation
This is the glycolysis component of Bioc (chem) 361 at UAE University. Some from Campbell 6th ed and the rest from General, Organic, and Biochemistry, 5th edition (2007), by K.J.Denniston, J.J.Topping, and R.L.Caret.
1) The Calvin cycle fixes carbon from carbon dioxide into organic molecules like glucose. It uses energy from light reactions to convert CO2 into glyceraldehyde-3-phosphate in chloroplasts.
2) The key enzyme is RuBisCO, which catalyzes the carboxylation of ribulose-1,5-bisphosphate with CO2 to form two molecules of 3-phosphoglycerate. These are then reduced and regenerated into more ribulose-1,5-bisphosphate in a cyclic process.
3) The cycle requires ATP and NADPH from light reactions. It is regulated by light and dark conditions that affect enzyme activation and pH levels in the chloroplast.
Digestion of glycolysis --Sir Khalid (Biochem)Soft-Learners
The document discusses digestion and absorption of carbohydrates. Carbohydrates taken in through the diet are broken down through digestion in the mouth, stomach, and small intestine by enzymes. Absorption occurs primarily in the small intestine. Glycolysis is then discussed, which is the breakdown of glucose within cells to extract energy. Glycolysis occurs in 10 steps involving multiple enzymes and produces pyruvate, ATP, and NADH.
The document discusses digestion and absorption of carbohydrates. Carbohydrates taken in through the diet are broken down through digestion in the mouth, stomach, and small intestine by enzymes. Absorption occurs primarily in the small intestine. Glycolysis is then discussed, which is the breakdown of glucose within cells to extract energy. Glycolysis occurs in 10 steps involving multiple enzymes and produces pyruvate, ATP, and NADH. Pyruvate can then be further broken down to lactate or enter the citric acid cycle.
Complete Set of Metabolism of Carbohydrate in that second chapter, glycolysis.
This presentation covers complete glycolysis pathway with step wise animated reactions and it includes clinical aspects also. This presentation is good for MBBS students.
Glycolysis is the pathway by which cells break down glucose to extract energy. Glucose first undergoes phosphorylation by hexokinase to form glucose-6-phosphate. A series of enzymatic reactions then convert glucose-6-phosphate through intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate, extracting energy in the form of ATP. Key steps include substrate-level phosphorylation by phosphofructokinase-1 and oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, reducing NAD+ to NADH. The pathway ultimately forms two pyruvate molecules from each glucose.
The document summarizes several metabolic pathways including:
1) The pentose phosphate pathway which generates NADPH and ribose-5-phosphate in the oxidative phase and converts intermediates to glycolysis in the nonoxidative phase.
2) Fructose metabolism which occurs mainly in the liver and bypasses regulation of glycolysis.
3) Galactose metabolism which is converted to glucose-1-phosphate in the liver.
Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors in the liver and kidneys. It occurs mainly in the liver and helps prevent hypoglycemia during fasting. While some of the same enzymes are used in both gluconeogenesis and glycolysis, three irreversible glycolysis reactions must be bypassed. The document provides details on the enzymes and reactions involved in bypassing these steps, including pyruvate carboxylase and PEP carboxykinase. Regulation ensures that gluconeogenesis and glycolysis do not operate simultaneously to avoid an energy-wasting cycle.
Glucose-6-phosphate acts as a branch point for several metabolic pathways. It can be used for glycolysis, glycogen synthesis, the hexose monophosphate shunt, and gluconeogenesis. The hexose monophosphate shunt generates NADPH for biosynthetic reactions through glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. NADPH is required for processes like fatty acid synthesis, cholesterol synthesis, and maintaining reduced glutathione levels in red blood cells. Glucose-6-phosphate dehydrogenase deficiency, which reduces NADPH production, provides some protection against malaria by shortening red blood cell lifespan.
1. The Calvin cycle fixes carbon dioxide into carbohydrates using energy from light reactions that produce ATP and NADPH.
2. Enzymes of the Calvin cycle regenerate the 5-carbon sugar RuBP from 3-carbon glyceraldehyde-3-P in chloroplasts.
3. Overall, 3 molecules of CO2 are fixed into one molecule each of two 3-carbon glyceraldehyde-3-P, with the remaining carbons recycled to regenerate 3 molecules of RuBP to continue the cycle.
This document summarizes glycolysis, the metabolic pathway that converts glucose into pyruvate. It describes the two phases of glycolysis - the preparatory phase which requires ATP, and the payoff phase which yields ATP and NADH. It also lists the three possible fates of the pyruvate produced: lactic acid fermentation, ethanol fermentation, or further processing in the citric acid cycle.
1. Glycolysis takes place in the cytosol and involves the conversion of glucose to glucose-6-phosphate through a reaction catalyzed by hexokinase using ATP as an energy source.
2. Glucose-6-phosphate then undergoes a series of reactions catalyzed by different enzymes to produce two molecules of pyruvate, involving phosphorylation, isomerization, and cleavage reactions.
3. These reactions initially require energy input in the form of ATP but later reactions produce ATP and NADH, which are used in downstream metabolic pathways.
The document discusses the hexose monophosphate shunt (HMP shunt), an alternative pathway to glycolysis and the TCA cycle for oxidizing glucose. The HMP shunt occurs in the cytosol and is more anabolic in nature, producing NADPH and pentose through oxidative and non-oxidative phases. Tissues with high HMP shunt activity like the liver, adipose tissue, and lactating mammary glands use the NADPH produced for biosynthesis of fatty acids and steroids.
Gluconeogenesis and glycolysis share many of the same enzymes but operate in opposite directions. Three irreversible steps in glycolysis - those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase - must be bypassed in gluconeogenesis. This is accomplished through different enzymes that catalyze reversible reactions, such as glucose-6-phosphatase and fructose-1,6-bisphosphatase. Regulation ensures that glycolysis and gluconeogenesis do not operate simultaneously, which would waste energy. Key control points include allosteric regulation by adenine nucleotides and hormonal stimulation of cAMP and protein phosphorylation.
1) The document summarizes key steps in glycolysis, beginning with the breakdown of glucose and ending with the production of pyruvate.
2) Glucose is phosphorylated by hexokinase to produce glucose-6-phosphate, then isomerized to fructose-6-phosphate and phosphorylated again to produce fructose-1,6-bisphosphate.
3) Fructose-1,6-bisphosphate is cleaved by aldolase into two trioses - glyceraldehyde-3-phosphate and dihydroxyacetone phosphate - with the release of energy in the form of ATP.
1) Dr. Khalid Alsharafa studies plant stress physiology, including how plants sense and respond to stresses like high light, temperature extremes, heavy metals, salinity, drought, and pathogens.
2) Plants have developed strategies to respond to stress, such as lowering reactive oxygen species production, scavenging ROS through antioxidants and enzymes, and signal transduction pathways that trigger stress responses.
3) Dr. Alsharafa's research aims to analyze post-transcriptional regulation of enzyme activity under abiotic stress of different durations and intensities, monitor plant acclimation to biotic and abiotic stresses over time, and detect retrograde signaling in response to abiotic stress.
Somatic hybridization involves fusing plant cell protoplasts (naked plant cells without cell walls) from two different plant species or varieties. This is done through isolating protoplasts enzymatically, fusing them using chemicals or electricity, selecting hybrid cells, culturing the hybrid cells, and regenerating hybrid plants. Somatic hybridization allows for the transfer of useful traits like disease resistance between sexually incompatible plant species. It has been used to create novel crop hybrids and backcross fertile somatic hybrids in plants like citrus and potatoes.
This document discusses different methods for predicting the secondary structure of proteins, including statistical methods like Chou-Fasman and GOR that use amino acid frequencies, and neural network methods like PHD that use multiple sequence alignments and training sets of known structures. It also briefly outlines experimental methods for determining protein structure like X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy.
- Evolution is the process of change over generations in inherited traits of organisms due to mutations, genetic recombination, and natural selection.
- Molecular phylogeny uses DNA and protein sequences to reconstruct evolutionary relationships and depict them in phylogenetic trees.
- Phylogenetic trees show how taxa are related through time with internal nodes representing common ancestors and branches representing elapsed time or genetic changes between nodes. Well-constructed phylogenetic trees are important for understanding the evolution and classification of living things.
This document discusses energy transformations in biology. It begins by explaining that energy transformations are linked to chemical reactions in cells, and the laws of thermodynamics apply. ATP plays a key role by capturing free energy from exergonic reactions and transferring it to power endergonic reactions. Enzymes lower the activation energy of reactions and are highly specific biological catalysts that use several mechanisms to facilitate chemical transformations in living systems. Enzyme activity can be regulated by inhibitors binding to the active site.
Mendeley is a free reference manager and academic social network that can help researchers organize, share, and discover research papers. It allows users to create a personal library by adding papers from their computer or online resources, collaborate with other researchers, and generate citations and bibliographies in Microsoft Word, OpenOffice, and LaTeX. The presentation introduced Mendeley's core features like adding documents, managing metadata, annotating papers, citing as you write, and synchronizing a library online.
The document discusses different modern methods of plant breeding including mutation breeding, polyploidy breeding, and haploidy breeding. It provides details on mutation breeding including how mutagens like radiation and chemicals can induce mutations and the process of mutation breeding from selection of material to development of new varieties. It also describes polyploidy breeding which involves variations in chromosome number like polyploids having more than two sets of genomes. Finally, it mentions how haploids which have only one set of chromosomes can be used in plant breeding through techniques like haploid production and chromosome doubling.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
2. Glycolysis takes place in the cytosol of cells.
Glucose enters the Glycolysis pathway by conversion
to glucose-6-phosphate.
Initially there is energy input corresponding to
cleavage of two ~P bonds of ATP.
H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
1
6
5
4
3 2
glucose-6-phosphate
3. H O
OH
H
OH
H
OH
CH2OH
H
OH
H H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
2
3
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
1. Hexokinase catalyzes:
Glucose + ATP glucose-6-P + ADP
The reaction involves nucleophilic attack of the C6
hydroxyl O of glucose on P of the terminal phosphate
of ATP.
ATP binds to the enzyme as a complex with Mg++.
4. Mg++ interacts with negatively charged phosphate
oxygen atoms, providing charge compensation &
promoting a favorable conformation of ATP at the
active site of the Hexokinase enzyme.
N
N
N
N
NH2
O
OH
OH
H
H
H
CH2
H
O
P
O
P
O
P
O
O
O
O
O O
O
adenine
ribose
ATP
adenosine triphosphate
5. The reaction catalyzed by Hexokinase is highly
spontaneous.
A phosphoanhydride bond of ATP (~P) is cleaved.
The phosphate ester formed in glucose-6-phosphate
has a lower DG of hydrolysis.
H O
OH
H
OH
H
OH
CH2OH
H
OH
H H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
2
3
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
6. the C6 hydroxyl of the
bound glucose is close to
the terminal phosphate of
ATP, promoting catalysis.
water is excluded from the active site.
This prevents the enzyme from catalyzing ATP
hydrolysis, rather than transfer of phosphate to glucose.
glucose
Hexokinase
H O
OH
H
OH
H
OH
CH2OH
H
OH
H H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
2
3
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
Induced fit:
Glucose binding
to Hexokinase
stabilizes a
conformation
in which:
7. It is a common motif for an enzyme active site to be
located at an interface between protein domains that are
connected by a flexible hinge region.
The structural flexibility allows access to the active site,
while permitting precise positioning of active site
residues, and in some cases exclusion of water, as
substrate binding promotes a particular conformation.
glucose
Hexokinase
8. 2. Phosphoglucose Isomerase catalyzes:
glucose-6-P (aldose) fructose-6-P (ketose)
The mechanism involves acid/base catalysis, with ring
opening, isomerization via an enediolate intermediate,
and then ring closure. A similar reaction catalyzed by
Triosephosphate Isomerase will be presented in detail.
H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
1
6
5
4
3 2
CH2OPO3
2
OH
CH2OH
H
OH H
H HO
O
6
5
4 3
2
1
glucose-6-phosphate fructose-6-phosphate
Phosphoglucose Isomerase
9. 3. Phosphofructokinase catalyzes:
fructose-6-P + ATP fructose-1,6-bisP + ADP
This highly spontaneous reaction has a mechanism similar
to that of Hexokinase.
The Phosphofructokinase reaction is the rate-limiting step
of Glycolysis.
The enzyme is highly regulated, as will be discussed later.
CH2OPO3
2
OH
CH2OH
H
OH H
H HO
O
6
5
4 3
2
1 CH2OPO3
2
OH
CH2OPO3
2
H
OH H
H HO
O
6
5
4 3
2
1
ATP ADP
Mg2+
fructose-6-phosphate fructose-1,6-bisphosphate
Phosphofructokinase
10. 4. Aldolase catalyzes: fructose-1,6-bisphosphate
dihydroxyacetone-P + glyceraldehyde-3-P
The reaction is an aldol cleavage, the reverse of an aldol
condensation.
Note that C atoms are renumbered in products of Aldolase.
6
5
4
3
2
1CH2OPO3
2
C
C
C
C
CH2OPO3
2
O
HO H
H OH
H OH
3
2
1
CH2OPO3
2
C
CH2OH
O
C
C
CH2OPO3
2
H O
H OH
+
1
2
3
fructose-1,6-
bisphosphate
Aldolase
dihydroxyacetone glyceraldehyde-3-
phosphate phosphate
Triosephosphate Isomerase
11. A lysine residue at the active site functions in catalysis.
The keto group of fructose-1,6-bisphosphate reacts with
the e-amino group of the active site lysine, to form a
protonated Schiff base intermediate.
Cleavage of the bond between C3 & C4 follows.
CH2OPO3
2
C
CH
C
C
CH2OPO3
2
NH
HO
H OH
H OH
(CH2)4 Enzyme
6
5
4
3
2
1
+
Schiff base intermediate of
Aldolase reaction
H3N+
C COO
CH2
CH2
CH2
CH2
NH3
H
lysine
12. 5. Triose Phosphate Isomerase (TIM) catalyzes:
dihydroxyacetone-P glyceraldehyde-3-P
Glycolysis continues from glyceraldehyde-3-P. TIM's Keq
favors dihydroxyacetone-P. Removal of glyceraldehyde-3-P
by a subsequent spontaneous reaction allows throughput.
6
5
4
3
2
1CH2OPO3
2
C
C
C
C
CH2OPO3
2
O
HO H
H OH
H OH
3
2
1
CH2OPO3
2
C
CH2OH
O
C
C
CH2OPO3
2
H O
H OH
+
1
2
3
fructose-1,6-
bisphosphate
Aldolase
dihydroxyacetone glyceraldehyde-3-
phosphate phosphate
Triosephosphate Isomerase
13. The ketose/aldose conversion involves acid/base catalysis,
and is thought to proceed via an enediol intermediate, as
with Phosphoglucose Isomerase.
Active site Glu and His residues are thought to extract and
donate protons during catalysis.
C
C
CH2OPO3
2
O
C
C
CH2OPO3
2
H O
H OH
C
C
CH2OPO3
2
H OH
OH
H
H OH H+
H+
H+
H+
dihydroxyacetone enediol glyceraldehyde-
phosphate intermediate 3-phosphate
Triosephosphate Isomerase
14. C
CH2OPO3
2
O O
C
CH2OPO3
2
HC O
OH
proposed
enediolate
intermediate
phosphoglycolate
transition state
analog
2-Phosphoglycolate is a transition state analog that
binds tightly at the active site of Triose Phosphate
Isomerase (TIM).
This inhibitor of catalysis by TIM is similar in structure to
the proposed enediolate intermediate.
TIM is judged a "perfect enzyme." Reaction rate is limited
only by the rate that substrate collides with the enzyme.
15. TIM
Triosephosphate Isomerase
structure is an ab barrel, or
TIM barrel.
In an ab barrel there are
8 parallel b-strands surrounded
by 8 a-helices.
Short loops connect alternating
b-strands & a-helices.
16. TIM
TIM barrels serve as scaffolds
for active site residues in a
diverse array of enzymes.
Residues of the active site are
always at the same end of the
barrel, on C-terminal ends of
b-strands & loops connecting
these to a-helices.
There is debate whether the many different enzymes with
TIM barrel structures are evolutionarily related.
In spite of the structural similarities there is tremendous
diversity in catalytic functions of these enzymes and
little sequence homology.
17. C
C
CH2OPO3
2
H O
H OH
C
C
CH2OPO3
2
O OPO3
2
H OH
+ Pi
+ H+
NAD+
NADH 1
2
3
2
3
1
glyceraldehyde- 1,3-bisphospho-
3-phosphate glycerate
Glyceraldehyde-3-phosphate
Dehydrogenase
6. Glyceraldehyde-3-phosphate Dehydrogenase
catalyzes:
glyceraldehyde-3-P + NAD+ + Pi
1,3-bisphosphoglycerate + NADH + H+
18. C
C
CH2OPO3
2
H O
H OH
C
C
CH2OPO3
2
O OPO3
2
H OH
+ Pi
+ H+
NAD+
NADH 1
2
3
2
3
1
glyceraldehyde- 1,3-bisphospho-
3-phosphate glycerate
Glyceraldehyde-3-phosphate
Dehydrogenase
Exergonic oxidation of the aldehyde in glyceraldehyde-
3-phosphate, to a carboxylic acid, drives formation of an
acyl phosphate, a "high energy" bond (~P).
This is the only step in Glycolysis in which NAD+ is
reduced to NADH.
19. A cysteine thiol at the active site of Glyceraldehyde-
3-phosphate Dehydrogenase has a role in catalysis.
The aldehyde of glyceraldehyde-3-phosphate reacts
with the cysteine thiol to form a thiohemiacetal
intermediate.
H3N+
C COO
CH2
SH
H
cysteine
C
C
CH2OPO3
2
H O
H OH
1
2
3
glyceraldehyde-3-
phosphate
20. The “high energy” acyl thioester is attacked by Pi to
yield the acyl phosphate (~P) product.
CH CH2OPO3
2
OH
Enz-Cys SH
Enz-Cys S CH CH CH2OPO3
2
OH
OH
Enz-Cys S C CH CH2OPO3
2
OH
O
HC
NAD+
NADH
Enz-Cys SH
Pi
C CH CH2OPO3
2
OH
O
O3PO
2
O
glyceraldehyde-3-
phosphate
1,3-bisphosphoglycerate
thiohemiacetal
intermediate
acyl-thioester
intermediate
Oxidation to a
carboxylic acid
(in a ~ thioester)
occurs, as NAD+
is reduced to
NADH.
21. Recall that NAD+ accepts 2 e plus one H+ (a hydride)
in going to its reduced form.
N
R
H
C
NH2
O
N
R
C
NH2
O
H H
+
2e
+ H
+
NAD+
NADH
22. C
C
CH2OPO3
2
O OPO3
2
H OH
C
C
CH2OPO3
2
O O
H OH
ADP ATP
1
2
2
3 3
1
Mg2+
1,3-bisphospho- 3-phosphoglycerate
glycerate
Phosphoglycerate Kinase
7. Phosphoglycerate Kinase catalyzes:
1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
This phosphate transfer is reversible (low DG), since
one ~P bond is cleaved & another synthesized.
The enzyme undergoes substrate-induced conformational
change similar to that of Hexokinase.
23. C
C
CH2OH
O O
H OPO3
2
2
3
1
C
C
CH2OPO3
2
O O
H OH
2
3
1
3-phosphoglycerate 2-phosphoglycerate
Phosphoglycerate Mutase
8. Phosphoglycerate Mutase catalyzes:
3-phosphoglycerate 2-phosphoglycerate
Phosphate is shifted from the OH on C3 to the
OH on C2.
24. C
C
CH2OH
O O
H OPO3
2
2
3
1
C
C
CH2OPO3
2
O O
H OH
2
3
1
3-phosphoglycerate 2-phosphoglycerate
Phosphoglycerate Mutase
C
C
CH2OPO3
2
O O
H OPO3
2
2
3
1
2,3-bisphosphoglycerate
An active site histidine side-chain
participates in Pi transfer, by
donating & accepting phosphate.
The process involves a
2,3-bisphosphate intermediate.
H3N+
C COO
CH2
C
HN
HC NH
CH
H
histidine
25. 9. Enolase catalyzes:
2-phosphoglycerate phosphoenolpyruvate + H2O
This dehydration reaction is Mg++-dependent.
2 Mg++ ions interact with oxygen atoms of the substrate
carboxyl group at the active site.
The Mg++ ions help to stabilize the enolate anion
intermediate that forms when a Lys extracts H+ from C #2.
C
C
CH2OH
O O
H OPO3
2
C
C
CH2OH
O O
OPO3
2
C
C
CH2
O O
OPO3
2
OH
2
3
1
2
3
1
H
2-phosphoglycerate enolate intermediate phosphoenolpyruvate
Enolase
26. 10. Pyruvate Kinase catalyzes:
phosphoenolpyruvate + ADP pyruvate + ATP
C
C
CH3
O O
O
2
3
1
ADP ATP
C
C
CH2
O O
OPO3
2
2
3
1
phosphoenolpyruvate pyruvate
Pyruvate Kinase
27. This phosphate transfer from PEP to ADP is spontaneous.
PEP has a larger DG of phosphate hydrolysis than ATP.
Removal of Pi from PEP yields an unstable enol, which
spontaneously converts to the keto form of pyruvate.
Required inorganic cations K+ and Mg++ bind to anionic
residues at the active site of Pyruvate Kinase.
C
C
CH3
O O
O
2
3
1
ADP ATP
C
C
CH2
O O
OPO3
2
2
3
1
C
C
CH2
O O
OH
2
3
1
phosphoenolpyruvate enolpyruvate pyruvate
Pyruvate Kinase
30. Glycolysis
Balance sheet for ~P bonds of ATP:
How many ATP ~P bonds expended? ________
How many ~P bonds of ATP produced? (Remember
there are two 3C fragments from glucose.) ________
Net production of ~P bonds of ATP per glucose:
________
2
4
2
31. Balance sheet for ~P bonds of ATP:
2 ATP expended
4 ATP produced (2 from each of two 3C fragments
from glucose)
Net production of 2 ~P bonds of ATP per glucose.
Glycolysis - total pathway, omitting H+:
glucose + 2 NAD+ + 2 ADP + 2 Pi
2 pyruvate + 2 NADH + 2 ATP
In aerobic organisms:
pyruvate produced in Glycolysis is oxidized to CO2
via Krebs Cycle
NADH produced in Glycolysis & Krebs Cycle is
reoxidized via the respiratory chain, with production
of much additional ATP.
32. They must reoxidize NADH produced in Glycolysis
through some other reaction, because NAD+ is needed for
the Glyceraldehyde-3-phosphate Dehydrogenase reaction.
Usually NADH is reoxidized as pyruvate is converted to
a more reduced compound.
The complete pathway, including Glycolysis and the
reoxidation of NADH, is called fermentation.
C
C
CH2OPO3
2
H O
H OH
C
C
CH2OPO3
2
O OPO3
2
H OH
+ Pi
+ H+
NAD+
NADH 1
2
3
2
3
1
glyceraldehyde- 1,3-bisphospho-
3-phosphate glycerate
Glyceraldehyde-3-phosphate
Dehydrogenase
Fermentation:
Anaerobic
organisms lack a
respiratory chain.
33. C
C
CH3
O
O
O
C
HC
CH3
O
OH
O
NADH + H+
NAD+
Lactate Dehydrogenase
pyruvate lactate
E.g., Lactate Dehydrogenase catalyzes reduction of
the keto in pyruvate to a hydroxyl, yielding lactate, as
NADH is oxidized to NAD+.
Lactate, in addition to being an end-product of
fermentation, serves as a mobile form of nutrient energy,
& possibly as a signal molecule in mammalian organisms.
Cell membranes contain carrier proteins that facilitate
transport of lactate.
34. C
C
CH3
O
O
O
C
HC
CH3
O
OH
O
NADH + H+
NAD+
Lactate Dehydrogenase
pyruvate lactate
Skeletal muscles ferment glucose to lactate during
exercise, when the exertion is brief and intense.
Lactate released to the blood may be taken up by other
tissues, or by skeletal muscle after exercise, and converted
via Lactate Dehydrogenase back to pyruvate, which may
be oxidized in Krebs Cycle or (in liver) converted to back
to glucose via gluconeogenesis
35. C
C
CH3
O
O
O
C
HC
CH3
O
OH
O
NADH + H+
NAD+
Lactate Dehydrogenase
pyruvate lactate
Lactate serves as a fuel source for cardiac muscle as
well as brain neurons.
Astrocytes, which surround and protect neurons in the
brain, ferment glucose to lactate and release it.
Lactate taken up by adjacent neurons is converted to
pyruvate that is oxidized via Krebs Cycle.
36. C
C
CH3
O
O
O
C
CH3
OH
C
CH3
O
H H
H
NADH + H+
NAD+
CO2
Pyruvate Alcohol
Decarboxylase Dehydrogenase
pyruvate acetaldehyde ethanol
Some anaerobic organisms metabolize pyruvate to
ethanol, which is excreted as a waste product.
NADH is converted to NAD+ in the reaction
catalyzed by Alcohol Dehydrogenase.
37. Glycolysis, omitting H+:
glucose + 2 NAD+ + 2 ADP + 2 Pi
2 pyruvate + 2 NADH + 2 ATP
Fermentation, from glucose to lactate:
glucose + 2 ADP + 2 Pi 2 lactate + 2 ATP
Anaerobic catabolism of glucose yields only 2 “high
energy” bonds of ATP.
38. Glycolysis Enzyme/Reaction
DGo'
kJ/mol
DG
kJ/mol
Hexokinase -20.9 -27.2
Phosphoglucose Isomerase +2.2 -1.4
Phosphofructokinase -17.2 -25.9
Aldolase +22.8 -5.9
Triosephosphate Isomerase +7.9 negative
Glyceraldehyde-3-P Dehydrogenase
& Phosphoglycerate Kinase
-16.7 -1.1
Phosphoglycerate Mutase +4.7 -0.6
Enolase -3.2 -2.4
Pyruvate Kinase -23.0 -13.9
*Values in this table from D. Voet & J. G. Voet (2004) Biochemistry, 3rd Edition, John
Wiley & Sons, New York, p. 613.
39. Flux through the Glycolysis pathway is regulated by
control of 3 enzymes that catalyze spontaneous reactions:
Hexokinase, Phosphofructokinase & Pyruvate Kinase.
Local control of metabolism involves regulatory effects
of varied concentrations of pathway substrates or
intermediates, to benefit the cell.
Global control is for the benefit of the whole organism,
& often involves hormone-activated signal cascades.
Liver cells have major roles in metabolism, including
maintaining blood levels various of nutrients such as
glucose. Thus global control especially involves liver.
40. Hexokinase is inhibited by product glucose-6-phosphate:
by competition at the active site
by allosteric interaction at a separate enzyme site.
Cells trap glucose by phosphorylating it, preventing exit
on glucose carriers.
Product inhibition of Hexokinase ensures that cells will
not continue to accumulate glucose from the blood, if
[glucose-6-phosphate] within the cell is ample.
H O
OH
H
OH
H
OH
CH2OH
H
OH
H H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
2
3
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
41. Glucokinase has a high KM for glucose.
It is active only at high [glucose].
One effect of insulin, a hormone produced when blood
glucose is high, is activation in liver of transcription of
the gene that encodes the Glucokinase enzyme.
Glucokinase is not subject to product inhibition by
glucose-6-phosphate. Liver will take up & phosphorylate
glucose even when liver [glucose-6-phosphate] is high.
H O
OH
H
OH
H
OH
CH2OH
H
OH
H H O
OH
H
OH
H
OH
CH2OPO3
2
H
OH
H
2
3
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
Glucokinase
is a variant of
Hexokinase
found in liver.
42. Glucokinase is subject to inhibition by glucokinase
regulatory protein (GKRP).
The ratio of Glucokinase to GKRP in liver changes in
different metabolic states, providing a mechanism for
modulating glucose phosphorylation.
43. Glucose-6-phosphatase catalyzes hydrolytic release of Pi
from glucose-6-P. Thus glucose is released from the liver
to the blood as needed to maintain blood [glucose].
The enzymes Glucokinase & Glucose-6-phosphatase, both
found in liver but not in most other body cells, allow the
liver to control blood [glucose].
Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.
Glucokinase,
with high KM
for glucose,
allows liver to
store glucose
as glycogen in
the fed state
when blood [glucose] is high.
44. High [glucose] within liver cells causes a transcription
factor carbohydrate responsive element binding protein
(ChREBP) to be transferred into the nucleus, where it
activates transcription of the gene for Pyruvate Kinase.
This facilitates converting excess glucose to pyruvate,
which is metabolized to acetyl-CoA, the main precursor
for synthesis of fatty acids, for long term energy storage.
C
C
CH3
O O
O
2
3
1
ADP ATP
C
C
CH2
O O
OPO3
2
2
3
1
phosphoenolpyruvate pyruvate
Pyruvate Kinase
Pyruvate Kinase, the
last step Glycolysis, is
controlled in liver partly
by modulation of the
amount of enzyme.
45. Phosphofructokinase is usually the rate-limiting step of
the Glycolysis pathway.
Phosphofructokinase is allosterically inhibited by ATP.
At low concentration, the substrate ATP binds only at
the active site.
At high concentration, ATP binds also at a low-affinity
regulatory site, promoting the tense conformation.
CH2OPO3
2
OH
CH2OH
H
OH H
H HO
O
6
5
4 3
2
1 CH2OPO3
2
OH
CH2OPO3
2
H
OH H
H HO
O
6
5
4 3
2
1
ATP ADP
Mg2+
fructose-6-phosphate fructose-1,6-bisphosphate
Phosphofructokinase
46. The tense conformation of PFK, at high [ATP], has lower
affinity for the other substrate, fructose-6-P. Sigmoidal
dependence of reaction rate on [fructose-6-P] is seen.
AMP, present at significant levels only when there is
extensive ATP hydrolysis, antagonizes effects of high ATP.
0
10
20
30
40
50
60
0 0.5 1 1.5 2
[Fructose-6-phosphate] mM
PFK
Activity
high [ATP]
low [ATP]
47. Inhibition of the Glycolysis enzyme Phosphofructokinase
when [ATP] is high prevents breakdown of glucose in a
pathway whose main role is to make ATP.
It is more useful to the cell to store glucose as glycogen
when ATP is plentiful.
Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.