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Questions and Answers
What percentage of all genes encode regulatory proteins?
What percentage of all genes encode regulatory proteins?
Which type of proteins makes up a significant portion of regulatory proteins in the cell?
Which type of proteins makes up a significant portion of regulatory proteins in the cell?
How many different protein kinases are identified in the typical cell?
How many different protein kinases are identified in the typical cell?
What capacity does a typical cell have in terms of protein synthesis?
What capacity does a typical cell have in terms of protein synthesis?
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Which statement about metabolites is correct?
Which statement about metabolites is correct?
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What is one of the roles of metabolic compartmentation in eukaryotic cells?
What is one of the roles of metabolic compartmentation in eukaryotic cells?
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Which isozyme is specifically mentioned as differing in kinetic or regulatory properties?
Which isozyme is specifically mentioned as differing in kinetic or regulatory properties?
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How can the glycolytic enzyme pyruvate kinase (PK) affect gene expression?
How can the glycolytic enzyme pyruvate kinase (PK) affect gene expression?
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What distinguishes isozymes from one another?
What distinguishes isozymes from one another?
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Which enzyme acts as an RNA-binding protein in the absence of its glycolytic substrate?
Which enzyme acts as an RNA-binding protein in the absence of its glycolytic substrate?
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What is the primary output of interlocking metabolic processes within a cell?
What is the primary output of interlocking metabolic processes within a cell?
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Which factor most directly influences enzyme activity at the subcellular level?
Which factor most directly influences enzyme activity at the subcellular level?
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What is a key change in enzyme activity that can result from hormonal influence?
What is a key change in enzyme activity that can result from hormonal influence?
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How does a change in diet from high carbohydrate to high fat affect liver function?
How does a change in diet from high carbohydrate to high fat affect liver function?
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How many general types of insulin response elements do humans possess?
How many general types of insulin response elements do humans possess?
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What is considered the top priority for maintaining cellular function?
What is considered the top priority for maintaining cellular function?
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What is the target concentration of ATP that cells strive to maintain?
What is the target concentration of ATP that cells strive to maintain?
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Which of the following methods does NOT influence the activity of enzymes in the cell?
Which of the following methods does NOT influence the activity of enzymes in the cell?
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What is the role of AMP-activated protein kinase (AMPK) in cellular metabolism?
What is the role of AMP-activated protein kinase (AMPK) in cellular metabolism?
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What is a significant indicator of a cell's energy status?
What is a significant indicator of a cell's energy status?
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What would likely happen if the concentration of ATP in a cell drops significantly?
What would likely happen if the concentration of ATP in a cell drops significantly?
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Which factors can activate AMP-activated protein kinase (AMPK)?
Which factors can activate AMP-activated protein kinase (AMPK)?
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How do regulatory mechanisms prevent simultaneous operation of glycolysis and gluconeogenesis?
How do regulatory mechanisms prevent simultaneous operation of glycolysis and gluconeogenesis?
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What is the effect of covalent modification on enzyme activity?
What is the effect of covalent modification on enzyme activity?
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What is one of the functions of allosteric regulation in metabolic pathways?
What is one of the functions of allosteric regulation in metabolic pathways?
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What is mainly reflected in the distribution of different isozymes of an enzyme?
What is mainly reflected in the distribution of different isozymes of an enzyme?
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Which cofactor ratios are crucial for the functioning of specific reactions within the cell?
Which cofactor ratios are crucial for the functioning of specific reactions within the cell?
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What is one potential consequence of accumulating products in a biosynthetic pathway?
What is one potential consequence of accumulating products in a biosynthetic pathway?
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Flashcards
Metabolic Regulation
Metabolic Regulation
The control of metabolic processes within a cell.
Thousands of Reactions
Thousands of Reactions
Cells catalyze many different biochemical processes.
Shared Metabolites
Shared Metabolites
Metabolic pathways share some intermediate molecules.
Regulatory Proteins
Regulatory Proteins
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Protein Kinases
Protein Kinases
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Enzyme Activity Regulation
Enzyme Activity Regulation
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Enzyme Regulation Mechanisms
Enzyme Regulation Mechanisms
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Hormone Response
Hormone Response
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Allosteric Control
Allosteric Control
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Covalent Modification
Covalent Modification
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Insulin's Role in Gene Regulation
Insulin's Role in Gene Regulation
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ATP Maintenance
ATP Maintenance
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Complexity of Gene Regulation
Complexity of Gene Regulation
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Isozymes
Isozymes
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Compartmentation
Compartmentation
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Hexokinase Isozymes
Hexokinase Isozymes
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Metabolic Enzymes & Location
Metabolic Enzymes & Location
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Non-metabolic Functions
Non-metabolic Functions
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AMP-activated protein kinase (AMPK)
AMP-activated protein kinase (AMPK)
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ATP/ADP ratio
ATP/ADP ratio
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AMP
AMP
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Adenylate Kinase
Adenylate Kinase
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Futile cycle
Futile cycle
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Allosteric regulation
Allosteric regulation
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Glycolysis vs. Gluconeogenesis
Glycolysis vs. Gluconeogenesis
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Study Notes
Metabolic Regulation
- Metabolic pathways involve thousands of different reactions catalyzed by 30,000 proteins in a typical cell.
- Metabolites are shared by one or more pathways.
- Approximately 12% of all genes encode regulatory proteins (4,000 genes).
- Receptors, regulators of gene expression, and 500 different protein kinases are involved in metabolic regulation.
- Interlocking metabolic processes are regulated simultaneously in cells.
- The right product, concentration, and time are essential for proper regulation.
Metabolism - the feat!
- Cells regulate interlocking metabolic processes simultaneously, despite external changes.
- Cells generate no leftovers during metabolic processes.
- Time scale for response to hormone or growth factors is hours; catalytic activity changes can happen in seconds to hours.
Factors affecting enzyme activity
- Extracellular signals, transcription factors, mRNA degradation, mRNA translation on ribosomes, protein degradation, and enzyme sequestration in subcellular organelles (e.g. endoplasmic reticulum) affect enzyme activity.
- Enzymes combine with regulatory proteins, undergo phosphorylation/dephosphorylation and bind to ligands affecting enzyme activity.
Alteration of enzyme activity
- Enzyme activity can change in response to hormones or growth factors.
- Rates of synthesis and degradation (time scale: hours to days) impact enzyme activity.
- Allosteric control (seconds to hours) and covalent modification (seconds to hours) modify catalytic activity.
Time Scales of Regulatory Mechanisms
- Availability of substrates: minutes
- Allosteric activation/inhibition of enzymes: minutes
- Covalent modification of enzymes: minutes to hours
- Synthesis of new enzyme molecules: hours to days
Insulin Regulated Genes
- Insulin regulates expression of various genes involved in pathways like glycolysis, gluconeogenesis, pentose phosphate pathway, and fatty acid synthesis.
- Increased expression of genes such as Hexokinase II, Phosphofructokinase-1, and Glucose-6-phosphate dehydrogenase is observed in response to insulin.
Insulin Regulation
- More than 150 genes are regulated by insulin.
- Insulin response elements (REs/IREs), involving specific transcription factors, mediate insulin's effect on gene expression.
Regulatory Input Into Genes
- The regulatory input into genes is complex, involving multiple transcription factors and response elements (e.g., HNF-4α, SREBP-1, PPARγ2, FOXO1, CREB, etc.) for specific genes.
ATP Maintenance
- Maintaining a constant supply and concentration of ATP (5-10 mM) is crucial for cell function.
- The ratio of ATP/ADP, NADH/NAD+, and NADPH/NADP+ are pivotal for reactions using these cofactors.
- AMP is a sensitive indicator of the cell's energy status, and AMP levels less than 0.1 mM indicate low energy within the cell
Adenine Nucleotides and Metabolic Regulation
- Many ATP-using enzymes have Km values between 0.1–1 mM.
- ATP concentration in a typical cell is ~5 mM.
- A drop in intracellular ATP concentration impacts numerous cellular reactions.
AMP-activated Protein Kinase (AMPK)
- Many regulatory processes are linked to AMP regulation, with AMPK playing a key role.
AMPK Signaling Pathway
- AMPK is activated by elevated AMP and/or decreased ATP.
- AMPK regulates metabolism through phosphorylation of target proteins, shifting metabolism from energy-consuming to energy-generating reactions.
General Regulatory Mechanisms
- Glycolysis and gluconeogenesis, operating in opposite directions, must be regulated to prevent futile cycles.
- Metabolites are partitioned among pathways (e.g., glycolysis and pentose phosphate pathway).
- Cells utilize fuel (e.g., glucose, fatty acids, glycogen, amino acids) best suited for immediate needs.
- Biosynthetic pathways are shut down when product accumulates.
Coordinated Regulation of Pathways (Glycolysis and gluconeogenesis)
- In futile cycles, both glycolysis and gluconeogenesis operate simultaneously consuming ATP without net reactions.
- Cells coordinate regulations of these two processes to avoid wasteful cycles.
Allosteric Regulation
- Allosteric regulation is very rapid (milliseconds).
- Allosteric regulation is triggered locally by changes in metabolite concentrations (substrate, product, or cofactors).
Covalent Modification
- Common mechanisms involve phosphorylation and dephosphorylation catalyzed by kinases and phosphatases.
- Phosphorylation alters enzyme activity through electrostatic changes, inhibitor movement, protein interactions and conformational changes.
Isoenzymes
- Isoenzymes (different forms of an enzyme) exhibit differing kinetic or regulatory proprieties, cofactor usage, subcellular distribution, and amino acid sequences.
- Isoenzyme variations are regulated by development stages, tissue location, metabolic patterns, and response to allosteric modifications.
- Examples include hexokinase and lactate dehydrogenase (LDH).
Compartmentation
- Physical separation of metabolic processes (e.g., fatty acid synthesis and degradation) within different cellular compartments is crucial.
- Compartmentation increases metabolite concentrations.
- Compartmentation reduces diffusion barriers allowing different environments(e.g pH and potential gradients for oxidative phosphorylation), assists metabolic control.
Location-Dependent Functions of Metabolic Enzymes
- Metabolic enzymes can fulfill non-metabolic functions based on their subcellular location (e.g. regulating gene expression, histone acetylation, substrate localization).
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Description
Test your knowledge on the roles of regulatory proteins in cellular processes. This quiz covers essential questions about gene regulation, protein kinases, and protein synthesis capacity. Ideal for biology students seeking to deepen their understanding of cellular mechanisms.