Regulation of Metabolism
Lesson Prepared Under MHRD project “National Mission on Education Through ICT” Discipline: Botany Paper: Plant Metabolism National Coordinator: Prof. S.C. Bhatla Lesson: Regulation of Metabolism Lesson Developer: Dhara Arora Department/College: Department of Botany, University of Delhi Lesson Reviewer: Prof. S.C. Bhatla Department/College: Department of Botany Language Editor: Vinee Khanna Department/College: Department of Genetics, University of Delhi South Campus. Lesson Editor: Dr Rama Sisodia, Fellow in Botany ILLL
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Regulation of Metabolism
Table of contents Lesson: Regulation of Metabolism
Introduction
Integrated metabolism
Key junction: Acetyl CoA
Regulation of metabolic pathways
Genetic control
Interconversion (covalent modifications)
Allosteric control
Modulation by ligands
Compartmentalization
Control sites of major metabolic pathways
Summary
Exercise/ Practice
Glossary
References/ Bibliography/ Further Reading
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Regulation of Metabolism
Learning outcomes: The student will be able to
Understand the importance of regulation of metabolism
Become familiar with the basics of integrated metabolism and understand how the pathways are closely integrated
Understand the crucial role of acetyl CoA in linkage of major metabolic pathways and regulation of metabolic fluxes
Describe the sources of generation and possible fates of acetyl CoA in a plant cell
Describe terms like inducer, repressor, effector
Discuss the diverse levels at which regulation of metabolism can take place within a cell
Understand and appreciate how regulation of pathways takes place even at genetic level
Understand the concept of feed-back regulation
Describe the regulatory points of major metabolic pathways
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Regulation of Metabolism
Introduction Metabolism is the sum of all the processes by which biomolecules are broken down and resynthesized to form a complex, in a highly regulated network of interdependent enzymatic reactions. Regulation of metabolism is one of the most remarkable features of living organisms, with each and every enzyme catalysed reaction in the cell undergoing some form of regulation. Inside a cell, no 'discrete' pathways take place, rather all the pathways are inextricably intertwined with each other. Since these metabolic pathways are integrated, it is essential that each pathway is able to sense the status of the other pathways to maintain optimal functioning in an organism. Regulation of metabolism is a multidimensional process operating at varied levels with the help of key regulating molecules and hence enzymes. In this chapter we will discuss the basic essential central themes of interconnected metabolism, role of acetyl CoA, levels of regulation of enzyme activity at transcriptional and functional levels.
Integrated metabolism The basic central themes in highly integrated metabolism are as follows:
1. ATP is universal energy currency: ATP serves as energy source for different processes due to its high phosphoryl transfer potential. The hydrolysis of a sufficient number of ATP molecules helps in making a thermodynamically unfavourable reaction sequence into a favourable one.
2. ATP is oxidation product of fuel molecules like glucose, fatty acids and amino acids: Acetyl CoA is a common intermediate formed as a result of oxidation of these fuel molecules. Acetyl CoA is further oxidized to CO 2 with the formation of NADH and FADH2. These are electron carrier molecules, which further help synthesize ATP by electron transfer chain localized in mitochondria.
3. In reductive biosynthesis, NADPH is major electron donor: Reductive power is needed to synthesize relatively more reduced products as compared to the precursors. So, the high potential electrons required for the same are provided by NADPH.
4. Common set of building blocks for construction of biomolecules: Only a small number of precursors are involved in the biosynthesis of diverse biomolecules. Same metabolic pathways are involved in the generation of ATP and NADPH, and biosynthesis of complex molecules. So, central metabolic pathways share both anabolic and catabolic roles.
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Regulation of Metabolism
5. Distinct biosynthetic and degradative pathways: The pathways for synthesis and breakdown are always distinct so as to make sure that the reaction sequence is thermodynamically favourable at all times. This enhances the effectiveness of metabolic control.
Key junction: Acetyl CoA Acetyl CoA provides one of the crucial key junctions which govern the flow of molecules in metabolic pathways. Acetyl CoA is a central metabolite in linking catabolism and anabolism through varied physiological processes. It can react "reversibly" in the degradation or synthesis of lipids, carbohydrates and amino acids in plants. Acetyl CoA requiring metabolism occurs in different cell compartments and since membranes are impermeable to this molecule, it is either synthesized within each
subcellular
compartment depending upon requirement, or is imported with the help of specific transporters. Major sources of this two-carbon unit molecules are the oxidative decarboxylation of pyruvate and the β-oxidation of fatty acids. Ketogenic amino acids can also lead to the formation of acetyl Co-A.
Figure: Flowchart depicting central role of acetyl CoA in varied metabolic pathways Source: In-house, ILLL Four possible fates of acetyl CoA are as follows: a) Complete oxidation of acetyl unit into CO2 by citric acid cycle b) Formation of 3-hydroxy-3-methylglutaryl CoA from three molecules of acetyl CoA Institute of Lifelong Learning, University of Delhi
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Regulation of Metabolism c) Export to the cytoplasm in the form of citrate for fatty acid biosynthesis d) Formation of glucose via gluconeogenesis Thus, acetyl CoA forms a major regulatory junction for varied pathways inside a cell and controls metabolic fluxes of molecules depending upon requirement of the cell to maintain homeostasis.
Regulation of Metabolic Pathways Activities of various enzymes mainly determine the flow of metabolites along a metabolic pathway. For the regulation of a pathway, change in the activity of the enzyme that catalyses the slowest step in the reaction sequence is required. These key enzymes in the metabolic pathways are the junctions, on which the regulatory mechanisms operate. Varied levels at which enzyme activity is independently regulated are as follows:
1. Genetic control Biosynthesis of an enzyme protein is influenced at the genetic level: a) Transcriptional control: It occurs by interventions in the synthesis of the
corresponding
mRNA
of
the
enzyme.
Regulatory
proteins
(transcription factors) are involved in the mediation of this control as they act directly on DNA. These regulatory proteins have their binding sites (control elements) localized in the regulatory segment on DNA, called promoter region. These regulatory proteins are further affected by metabolites or hormones.
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Regulation of Metabolism
Figure: Binding of an activator or a repressor protein modulating the transcription of a gene in a positive or a negative manner. Txn: transcription Source: http://employees.csbsju.edu/hjakubowski/classes/ch331/bind/olbindtransciption.html An increased synthesis of a protein due to alteration at transcription level is called induction and similarly, reduced or suppressed synthesis is called repression. Depending upon the result of transcriptional regulation, these regulatory proteins may be referred to as a repressor or an inducer. The effects caused by transcription factors are usually reversible, being controlled by ligands or by interconversion. b) Translational control: Regulation of enzyme activity and titre occurs even at translational level. Stability of messenger RNAs and resistance of mRNAs against degradation by cellular ribonucleases varies. Rates of synthesis and degradation of a given mRNA decide the amount of the same mRNA in the cell. Further the rate of translation of mRNA by ribosomes is regulated by several factors. Even after synthesis, lifetime of a protein molecule is finite,
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Regulation of Metabolism ranging from few minutes to many days. This rate of protein degradation is specific to the type of protein and is dependent on cell conditions.
Figure: Translational control also plays a crucial role in metabolic regulation Source: http://en.wikipedia.org/wiki/Regulation_of_gene_expression
2. Interconversion (Covalent modifications) In this case, enzyme is present at its site of effect but is initially still inactive. Depending upon requirement of the cell, it can be converted into catalytically active form after signalling and mediation from second messenger through an activation enzyme. Furthermore, if the enzyme is no longer required, it can be returned to its inactive resting state by an inactivating enzyme. Interconversion usually involves an ATP-dependent phosphorylation of the enzyme protein. This phosphorylation is carried out by a protein kinase and its reversal dephosphorylation is carried out by a protein phosphatase. Generally, the phosphorylated form of the key enzyme is the more active form but it can be vice-versa too. These covalent modifications of enzyme proteins usually last longer (from seconds to minutes) as compared to reversible allosteric interactions (from milliseconds to seconds).
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Regulation of Metabolism
Figure: Protein kinases catalyse the transfer of a phosphate group onto a specific amino acid chain of substrate and phosphatases remove the phosphate group so that the protein returns to its basal state. Source: Ms Vinee Khanna
3. Allosteric control Many enzymes are regulated by allosteric control by effectors that are often substrates, products, or coenzymes of the pathway. They do not bind at the active centre of the enzyme, but at another site called allosteric site and modulate enzyme activity. Allosteric activators are effectors that enhance the protein's activity and allosteric inhibitors decrease the protein's activity. Allosteric activators enhance the attraction between substrate molecules and other binding sites whereas allosteric inhibitors decrease the affinity for substrate at other active sites.
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Regulation of Metabolism
Figure: Allosteric activators bind to allosteric site and enhance the rate of catalysis whereas allosteric inhibitors binding to allosteric site and decrease the rate of catalysis. Source: http://cnx.org/contents/3270ba1a-e262-481e-9902-61ef811251d5@6/Enzymes
Figure: The regulation pathway of Phosphoenolpyruvate (PEP) carboxylase Source: http://en.wikipedia.org/wiki/Phosphoenolpyruvate_carboxylase
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Regulation of Metabolism
4. Modulation by ligands The key enzymes can be regulated by ligands (substrates, products, coenzymes or other effectors). Precursor availability regulates the flow through a metabolic pathway. The increased activity of metabolic pathways that form a precursor increases the availability of the precursor and also the increased activity of metabolic pathways that consume the precursor, leads to decreased availability of precursor. The availability of the precursor can also be restricted by its subcellular localization. Limiting effect can also be due to coenzyme availability. The speed of a second pathway which is involved in regeneration of the coenzyme can limit the speed of first one. For example, availability of NAD+ being regenerated by respiratory electron transport chain, regulates both glycolysis and citric acid cycle. Immediate reaction products or end products of the reaction or metabolites of entirely different pathways can regulate enzyme activity in a pathway in varied ways. When the end products of a reaction are involved in regulation, it is called "feed-back" inhibition. Also precursors of a reaction chain are capable of stimulating their own utilization through activation of enzyme activity.
Figure: The end product of reaction sequence acts as inhibitor by binding to allosteric site and regulates enzyme activity Source: http://cnx.org/contents/3270ba1a-e262-481e-9902-61ef811251d5@6
5. Compartmentalization The presence of cell compartments in eukaryotes markedly affects the metabolic pattern. The fate of certain molecules is dependent on their location. For example, when energy is required, fatty acids are imported into mitochondria for their degradation. Institute of Lifelong Learning, University of Delhi
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Regulation of Metabolism
Figure: Schematic illustration showing the intracellular compartmentalization of some of the major metabolic pathways Source: Dr Manju A. Lal
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Regulation of Metabolism
Figure: Pathways showing basic regulation mechanisms of metabolism in a cell. Source: Institute of Lifelong Learning, University of Delhi
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Regulation of Metabolism
Control sites of major metabolic pathways The principal control sites of major pathways of metabolism are as follows: 1) Glycolysis This pathway localized in cytoplasm leads to the conversion of one molecule of glucose into two molecules of pyruvate along with the generation of two molecules each of ATP and NADH. For glycolysis to proceed, NAD + consumed in the reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase must be regenerated. Phosphofructokinase is the most important control site for this pathway. Higher levels of ATP inhibit phosphofructokinase and this inhibitory effect is enhanced by citrate and reversed by AMP.
Figure: Phosphofructokinase (PFK) is one of the primary control step in glycolysis. This enzyme is activated by AMP and fructose-2,6-bisphosphate, and inhibited by ATP and citrate. Source: http://plantphys.info/plant_physiology/enzymekinetics.shtml
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Regulation of Metabolism 2) Citric acid cycle and oxidative phosphorylation This common pathway for the oxidation of carbohydrates, fatty acids and amino acids, takes place in mitochondria, with acetyl CoA being the common entry point for most molecules. Complete oxidation of an acetyl unit by this cycle generates one molecule of GTP and four pairs of electrons in the form of three molecules of NADH and one molecule of FADH2. These electrons enter electron transport chain and lead to the synthesis of nine molecules of ATP. The electron donors are oxidized and then recycled back into the cycle if ADP is simultaneously phosphorylated to ATP. This is respiratory control and ensures that the rate of citric acid cycle is in accordance with the need for ATP. If ATP is present in abundance, the activities of two enzymes in the cycle- isocitrate dehydrogenase and α-ketoglutarate dehydrogenase are diminished.
Figure: Excess ATP diminishes the activities of isocitrate dehydrogenase and αketoglutarate dehydrogenase, which act as control points of citric acid cycle. Source:
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Regulation of Metabolism 3) Pentose phosphate pathway This pathway takes place in cytosol in two stages. In the first stage, oxidative decarboxylation of glucose-6-phosphate occurs, leading to the synthesis of two NADPH molecules for the reductive biosynthesis and the formation of ribose 5phosphate for the synthesis of nucleotides. Dehydrogenation of glucose 6phosphate is the control point of this pathway, which is controlled by the level of NADP+, an electron acceptor.
Figure: Availability of the substrate glucose-6-phosphate and NADP+ acts as important regulation factor for the pentose phosphate pathway. Source:
http://biocadmin.otago.ac.nz/fmi/xsl/bioc2/learnbitslecture.xsl?-
db=BIOC2web.fp7&-lay=Lectures&-recid=5157&-find 4) Gluconeogenesis Glucose can be synthesized from non-carbohydrate precursors such as amino acids, and the major entry point for such synthesis is pyruvate, which is carboxylated to oxaloacetate in mitochondria. Gluconeogenesis and glycolysis are usually reciprocally regulated so that one of them is minimally active and the other one is highly active. For e.g., fructose 1,6-bisphosphate, an essential enzyme in gluconeogenesis, is inhibited by AMP and activated by citrate whereas these molecules have opposite effects on phosphofructokinase, the control point of glycolysis.
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Regulation of Metabolism
Figure: Fructose-1,2-bisphosphatase acts as the control point of gluconeogenesis as it reverses the reaction catalysed by phosphofructokinase. Source:http://biocadmin.otago.ac.nz/fmi/xsl/bioc2/learnbitslecture.xsl?db=BIOC2web.fp7&-lay=Lectures&-recid=5157&-find
5) Fatty acid synthesis and degradation Synthesis of fatty acids in the cytosol occurs by the addition of two-carbon units to a growing chain on an acyl carrier protein. The citrate in the cytosol stimulates acetyl CoA carboxylase, an important enzyme in the pathway. Abundance of ATP and acetyl CoA enhances the level of citrate and thereby accelerates the rate of synthesis of fatty acids. The rate of degradation of fatty acids is coupled to the need for ATP. Fatty acid degradation is inhibited by malonyl CoA, the precursor for fatty acid synthesis, by preventing the translocation of fatty acids into mitochondria.
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Regulation of Metabolism
Figure: The enzyme acetyl CoA carboxylase if the primary control factor of fatty acid synthesis Source: http://biocadmin.otago.ac.nz/fmi/xsl/bioc2/learnbitslecture.xsl?db=BIOC2web.fp7&-lay=Lectures&-recid=5157&-find
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Regulation of Metabolism
Figure: A combination of various pathways in a photosynthetic cell. The carbon molecule is converted to starch and sucrose via intermediate pathways as shown. BE, branching enzyme; cBAM, pBAM, cytosolic and plastidial beta-amylase; CBB; Calvin–Benson– Bassham; CS, cellulose synthase; DB, debranching enzyme; DHAP; dihydroxyacetone phosphate; Fru, fructose; cFBPase, pFBPase, cytosolic and plastidial Fructose-1,6-bisphosphate phosphatase; FK, fructokinase; FT, fructosyl-transferase; Glu, glucose; G6P, glucose-6P; G1P, glucose-1P; GT, glucose transporter; GWD, glucan water dikinase; cHxk, mHxk, nHxk, pHxk, cytosolic, mitochondrial, nuclear, and plastidial hexokinase; cInv, cwInv, pInv, vInv, cytosolic, cell wall, plastidial, and vacuolar invertase; Malt, maltose; Mex1, maltose exporter; Pi, inorganic phosphate; PPi, pyrophosphate; Pyr, pyruvate; S6P, sucrose-6-P; SBPase, sedoheptulose-1,7bisphosphate phosphatase; SPP, sucrose-6-P phosphatase; SPS, sucrose-6-P synthase; SS, starch synthase; SUS, sucrose synthase; SUT, sucrose transporter; Tre, trehalose; T6P,
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Regulation of Metabolism
Trehalose-6-phosphate; TCA, tricarboxylic acid cycle; TPP, trehalose-6-p phosphatase; TPT, triose-P translocator; VDAC, voltage dependant anion channel. Source: http://journal.frontiersin.org/Journal/10.3389/fpls.2012.00306/full
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Regulation of Metabolism
Summary Metabolic pathways are enzyme-catalysed reactions in a sequential order, taking place in different cellular locations. The regulation of activities of enzymes which catalyse ratedetermining steps in metabolic pathways, help in controlling the flux of metabolites. All primary metabolic pathways are interlinked and hence share common metabolite pool of the cell. Acetyl CoA is an important key junction which links several anabolic and catabolic processes. Cells can regulate their metabolism by numerous mechanisms which range over a time scale of less than a millisecond to few days. This regulation is carried out by either changing the number of molecules of a specific enzyme or by changing the activity of existing enzyme. Regulation can be carried out at both genetic and functional level by altering the rate of transcription or translation, or by covalent modifications of enzyme molecule or by modulating the ligands or by specialized compartmentalization of the key enzymes, or by controlling the binding of effectors at allosteric site. These regulatory mechanisms can have either a positive or negative effect on the rate of enzyme-catalysed reactions in a metabolic pathway.
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Regulation of Metabolism
Exercises 1. State whether the following are true or false and justify your answer i.
Phosphatases are involved in catalytic transfer of a phosphate group onto an amino acid of a protein.
ii.
ATP is the major electron donor in the reductive biosynthesis pathways in a cell.
iii.
Allosteric activators enhance attraction between substrates and binding regions on enzymes.
iv.
Regulation cause by transcription factors is usually irreversible.
v.
Only enzyme-specific substrates bind to allosteric site of that enzyme. Ans. i. False, ii. False, iii. True, iv. False v. False
2. Fill in the blanks i.
Regulatory proteins bind to specific regions called __________, which are regulatory regions of DNA.
ii.
________ cause enzymatic degradation of messenger RNAs in the cytosol
iii.
Regulation of metabolism can take place at both the levels, ______ and ______.
iv.
__________
is
crucial
junction
in
linking
varied
anabolic
and
catabolic
physiological processes. v.
___________ pathway involves oxidation of carbohydrates, fatty acids and amino acids.
vi.
Pentose phosphate pathway takes place in two stages which take place in _________.
Ans. i. promoters, ii. ribonucleases iii. genetic and functional iv. Acetyl CoA, v. Citric acid cycle, vi. cytosol 3. Multiple choice questions i.
The mechanism of regulation by which end products control the rate of reactions of a pathway is called: a. Product inhibition b Feedback inhibition
c. Compartmentalization d. Genetic control
Correct answer: b
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Regulation of Metabolism Feedback for answer: a. There is no such mechanism, called product inhibition. b. Feedback inhibition refers to inhibition of an enzyme which catalyses the
production
of particular substance in the cell when that substance has accumulated to a certain level. c. Compartmentalization refers to spatial separation of various metabolic pathways or part of pathways in various organelles with a cell. d. Genetic control operates at transcriptional and translational level to regulate the overall titre of a protein
ii.
ATP is universal energy currency due to a. Its high phosphoryl transfer potential b. Its high abundance in the cell c. Its ubiquitous presence in the cell d. Its involvement in numerous metabolic reactions Correct answer: a Feedback for answer:
a. ATP serves as energy source for different processes due to its high phosphoryl transfer potential. b. Abundance of ATP depends upon the metabolic state of a cell. c. ATP is ubiquitously present in the cells but that does not justify its status as energy currency. d. ATP is involved in numerous metabolic reactions but that does not justify its status as energy currency.
iii. Following pathways are reversibly regulated: a. Citric acid cycle and glycolysis b. Gluconeogenesis and glycolysis c. Citric acid cycle and gluconeogenesis d. All of the above
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Regulation of Metabolism Correct answer: c Feedback for answer: a. Citric acid cycle and glycolysis are not reversible in nature. b. Gluconeogenesis and glycolysis are not reversibly regulated. c. Citric acid cycle and gluconeogenesis are reversibly regulated d. Option a and b are incorrect. iv. Regulation of metabolism at genetic involves: a. Transcriptional control only b. Translational control only c. Transcriptional and translational control d. None of the above Correct answer: c Feedback for answer: a. Genetic level regulation involves translational control as well. b. Genetic level regulation involves transcriptional control as well. c. Genetic level regulation involves both transcriptional and translational control. d. Option c is correct.
v. Fatty acid degradation is inhibited by a. ATP
c. Malonyl CoA
b. Acetyl CoA
d. NADPH
Correct answer: c Feedback for answer: a. ATP enhances the level of citrate and thus increases the rate of synthesis of fatty acids. b. Acetyl CoA enhances the level of citrate and thus increases the rate of synthesis of fatty acids. c. Malonyl CoA is the precursor for fatty acid synthesis and prevents degradation of fatty acids. Institute of Lifelong Learning, University of Delhi
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Regulation of Metabolism d. NADPH does not affect fatty acid degradation as such. vi. Which of the following is not a source of acetyl CoA? a. Glucogenic amino acids b. Oxidative decarboxylation of pyruvate c. β-oxidation of fatty acids d. Ketogenic amino acids Correct answer: a Feedback for answer: a. Glucogenic amino
acids degradation
results in
formation of various carbon
compounds. b. Oxidative decarboxylation of pyruvate results in formation of acetyl CoA. c. β-oxidation of fatty acids results in production of acetyl CoA. d. Ketogenic amino acids degradation results in formation of acetyl CoA. vii. The effects caused by transcription factors are reversibly controlled by: a. Promoters
c. Allosteric control
b. Ligands and interconversion
d. None of the above
Correct answer: b Feedback for answer: a. Promoters are segments of DNA which usually occurs upstream from a gene coding region. They act as a control element in the transcription of that gene. b. Ligands and interconversion help in reversible regulation of effects of transcription factors. c. Allosteric control generally modulates enzyme activity by binding of effectors to allosteric site. d. Option b is correct. viii. A thermodynamically unfavourable reaction sequence can be converted to a favourable one by: a. Hydrolysis of sufficient number of ATP molecules b. Providing high potential electrons by NADPH c. Allosteric modulation d. All of the above Institute of Lifelong Learning, University of Delhi
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Regulation of Metabolism
Correct answer: a Feedback for answer: a. Hydrolysis of sufficient number of ATP molecules releases enough energy for conversion of a thermodynamically unfavourable reaction sequence to a favourable one. b. High potential electrons are not able to provide energy to cause conversion of thermodynamically unfavourable reaction sequence to a favourable one. c. Allosteric modulation alters an enzyme's activity. d. Option b and c are incorrect.
ix. Oxidation of acetyl CoA leads to the production of CO2 along with: a. Only ATP
c. ATP and NADH
b. FADH2 and ATP
d. NADH and FADH2
Correct answer: d Feedback for answer: a. ATP is not formed on oxidation of acetyl CoA leading to the production of CO 2. b. ATP is not formed on oxidation of acetyl CoA leading to the production of CO2.. c. ATP is not formed on oxidation of acetyl CoA leading to the production of CO2.. d. NADH and FADH2 are formed on oxidation of acetyl CoA leading to the production of CO2.. x. Which of the following is not a possible fate of acetyl CoA? a. Complete oxidation of acetyl unit into CO2 by citric acid cycle b. Export to plastids in the form of citrate c. Formation of 3-hydroxy-3-methylglutaryl CoA from three molecules of acetyl CoA d. Formation of glucose via gluconeogenesis Correct answer: b
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Regulation of Metabolism Feedback for answer: a. Acetyl CoA can be completely oxidized into CO2 by citric acid cycle. b. Acetyl CoA is not exported to plastids in the form of citrate. c. 3-hydroxy-3-methylglutaryl CoA is formed from three molecules of acetyl CoA. d. Acetyl CoA can lead to formation of glucose via gluconeogenesis
4. Match the following
Column A
Column B
Feedback inhibition
Energy currency
Acetyl CoA
Product accumulation
Kinases
Phosphorylation
ATP
Ketogenic amino acids
Ans: 1 (b), 2 (d), 3 (c), 4 (a). 5. Short answer type questions i. Distinguish between a. Allosteric activators and allosteric inhibitors b. Kinases and phosphatases c. Inducer and repressor ii. Describe the control points of major metabolic pathways in a cell. iii. Write a short note on the role of acetyl CoA in integrated metabolism in a cell. iv. Write short note on a. Allosteric site b. Covalent modifications c. Feedback inhibition vi.
Describe various schemes that enumerate upon the fact that metabolic pathways in a cell are closely integrated.
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Regulation of Metabolism
Glossary Active centre: The region of an enzyme molecule in which the reactive groups are juxtaposed and the chemical reaction takes place. It is also called active site. Allosteric site: It is a site on a multi-subunit enzyme where a molecule that is not a substrate may bind and induce a reversible conformational change resulting in alteration of catalytic properties of enzyme. Anabolism: It is the constructive phase of metabolism in which simple substances are converted into more complex compounds of living matter. Catabolism: It is the degradative phase of metabolism in which complex molecules are broken into simple ones. Dephosphorylation : It is the removal of a phosphate group from an organic compound by chemically or enzymatically. Feedback inhibition: It refers to inhibition of an enzyme which catalyses the production of particular substance in the cell when that substance has accumulated to a certain level. Gluconeogenesis: It is a metabolic pathway in which non-carbohydrate carbon substrates, such as pyruvate, lactate, glycerol, glucogenic amino acids and fatty acids, are converted to glucose Glycolysis: A metabolic process in which glucose and other sugars are converted into pyruvate with the release of energy in the form of ATP. Homeostasis: It is a relatively stable state of equilibrium that allows the maintenance and regulation of the stability and constancy of a cell or tissue or organ to function properly, by adjusting the physiological processes. Hydrolysis: It is a type of decomposition reaction in which chemical breakdown of a compound takes place due to reaction with water. Inducer: A factor that increases the metabolic activity of an enzyme either by enhancing the expression of the gene coding the enzyme or by binding to the enzyme and activating it. Ketogenic amino acid: An amino acid that can be degraded directly into acetyl CoA by the process of ketogenesis. Kinase: Any group of enzymes that catalyse the transfer of a phosphate group to bring about phosphorylation of a molecule. Ligand: An ion or an molecule or a molecular group that forms a larger complex by binding to another chemical entity. Metabolic flux: It is rate of turnover of molecules in a metabolic pathway under the regulation of enzymes involved in the pathway. Metabolite pool: It is a collective term which includes all of the substances involved in the metabolic process in a biological system.
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Regulation of Metabolism Metabolism: It is sum of all the processes by which biomolecules are broken down and resynthesized to form a complex, in a highly regulated network of interdependent enzymatic reactions. Oxidation: It is the loss of electrons by a molecule, atom or ion during a reaction leading to an increase in oxidation state. Oxidative Phosphorylation: It is a metabolic pathway taking place in mitochondria in which energy is released by oxidation of metabolites to synthesize the energy-rich molecule ATP. Phosphatase: Any group of enzymes that catalyse the cleavage of inorganic phosphate from ester compounds by the process of hydrolysis. Phosphorylation: It is a biochemical process that involves the addition of a phosphate group to an organic compound. Precursor: A biochemical substance that is transformed into another compound during the course of a chemical reaction. Promoter: It is a segment of DNA which usually occurs upstream from a gene coding region. It acts as a control element in the transcription of that gene. Reduction: It is the gain of electrons by a molecule, atom or ion during a reaction leading to an increase in reduction state. Regulatory proteins: They are proteins which bind to specific regulatory sequences of DNA and result in switching on and off of genes thereby regulating transcription of genes. Repressor: It is a factor that binds to the operator gene and shuts off the expression of the structural genes of an operon. Ribonucleases: It is a type of nuclease that catalyses the breakdown of RNA into smaller compounds by hydrolysis. Also called RNase. Secondary messengers: They are intracellular signalling molecules which act as an messenger after a hormone binds to cell-surface receptors. Transcription: It is the process in a cell by which messenger RNA is synthesized from a DNA template resulting in the transfer of genetic information from the DNA molecule to the messenger RNA. Transcription factors: A diverse family of proteins which generally function in multisubunit protein complexes and control when genes are switched on or off. They may bind directly to promoter regions of DNA or to RNA polymerase molecule. Translation: It is the process in the ribosomes of a cell by which messenger RNA directs the amino acid sequence of a growing peptide during protein synthesis.
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Regulation of Metabolism
References Lehninger Principles of Biochemistry (2008) 5th ed. Nelson D and Cox . W.H. Freeman & Co. Ltd, New York Biochemistry (2002) 5th ed. Berg JM, Tymoczko JL and Stryer L. W.H. Freeman & Co. Ltd, New York Fundamentals of Biochemistry (2008) 3rd ed. Voet D, Judith GV and Pratt CV. John Wiley & Sons, USA Color Atlas of Biochemistry (2005) 2nd ed. Koolman J and Roehm KH. Thieme Sttuttgart, New York
Weblinks http://www.sciencedirect.com/science/article/pii/S136013850400295X http://www.plantphysiol.org/content/152/2/428 http://books.google.co.in/books?id=9VHc1y3WeZgC&pg=PA176&lpg=PA176&dq=regulat ion+of+metabolism+in+plants&source=bl&ots=u4hcqqMWf4&sig=Lh_o_pemlLyd51B_PqeFrhp7rc&hl=en&sa=X&ei=pt9AVM66GMTXmAXFg4KoAQ&ved=0CFoQ6AE wCTgo#v=onepage&q=regulation%20of%20metabolism%20in%20plants&f=false http://journal.frontiersin.org/Journal/10.3389/fpls.2012.00306/full
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