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Questions and Answers
Which glucose transporter is responsible for transporting glucose across the blood-brain barrier?
Which glucose transporter is responsible for transporting glucose across the blood-brain barrier?
What is the primary function of GLUT-5?
What is the primary function of GLUT-5?
How does GLUT-2 function when blood glucose levels are low?
How does GLUT-2 function when blood glucose levels are low?
What characterizes facilitated diffusion in glucose transport?
What characterizes facilitated diffusion in glucose transport?
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Which glucose transporter is insulin dependent?
Which glucose transporter is insulin dependent?
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What happens during the energy-generation phase of glycolysis?
What happens during the energy-generation phase of glycolysis?
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Which of the following statements about sodium-dependent glucose transport is true?
Which of the following statements about sodium-dependent glucose transport is true?
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Why do phosphorylated sugars not easily penetrate membranes?
Why do phosphorylated sugars not easily penetrate membranes?
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What is the main function of catabolic pathways?
What is the main function of catabolic pathways?
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Which statement accurately describes the difference between catabolism and anabolism?
Which statement accurately describes the difference between catabolism and anabolism?
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What is the end product of anaerobic glycolysis?
What is the end product of anaerobic glycolysis?
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Which metabolic feature is often needed for anabolic reactions?
Which metabolic feature is often needed for anabolic reactions?
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What role does glycolysis play in glucose metabolism?
What role does glycolysis play in glucose metabolism?
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What is an essential consequence of a blockage in metabolic pathways?
What is an essential consequence of a blockage in metabolic pathways?
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Which process describes aerobic glycolysis?
Which process describes aerobic glycolysis?
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What term describes the pathways that synthesize complex molecules from simpler ones?
What term describes the pathways that synthesize complex molecules from simpler ones?
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What is the primary role of glyceraldehyde 3-phosphate dehydrogenase in glycolysis?
What is the primary role of glyceraldehyde 3-phosphate dehydrogenase in glycolysis?
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What condition results from pentavalent arsenic poisoning in terms of glycolysis?
What condition results from pentavalent arsenic poisoning in terms of glycolysis?
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What activates pyruvate kinase in glycolysis?
What activates pyruvate kinase in glycolysis?
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What is the major fate of pyruvate in poorly vascularized tissues?
What is the major fate of pyruvate in poorly vascularized tissues?
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Why do individuals heterozygous for PK deficiency have resistance to severe malaria?
Why do individuals heterozygous for PK deficiency have resistance to severe malaria?
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What mechanism maintains glycolysis in the cell when NAD+ levels are low?
What mechanism maintains glycolysis in the cell when NAD+ levels are low?
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What is the final product of anaerobic glycolysis in eukaryotes?
What is the final product of anaerobic glycolysis in eukaryotes?
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What condition may result from an elevated concentration of lactate in plasma?
What condition may result from an elevated concentration of lactate in plasma?
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What is the primary role of hexokinase in glycolysis?
What is the primary role of hexokinase in glycolysis?
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How does hexokinase IV (glucokinase) differ from hexokinase 1-III?
How does hexokinase IV (glucokinase) differ from hexokinase 1-III?
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What regulates the activity of glucokinase in the liver?
What regulates the activity of glucokinase in the liver?
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What is the primary function of phosphofructokinase-1 (PFK-1) in glycolysis?
What is the primary function of phosphofructokinase-1 (PFK-1) in glycolysis?
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What is the effect of high levels of ATP on phosphofructokinase-1 activity?
What is the effect of high levels of ATP on phosphofructokinase-1 activity?
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Which of the following statements about the isomerization of glucose 6-phosphate is true?
Which of the following statements about the isomerization of glucose 6-phosphate is true?
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What immediate products result from the cleavage of fructose 1,6-bisphosphate by aldolase?
What immediate products result from the cleavage of fructose 1,6-bisphosphate by aldolase?
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What is the role of fructose 2,6-bisphosphate in the regulation of glycolysis?
What is the role of fructose 2,6-bisphosphate in the regulation of glycolysis?
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What is the energy yield from anaerobic glycolysis per molecule of glucose?
What is the energy yield from anaerobic glycolysis per molecule of glucose?
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Which enzyme regulation is directly influenced by insulin in glycolysis?
Which enzyme regulation is directly influenced by insulin in glycolysis?
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What is one of the three major types of regulation in glycolysis?
What is one of the three major types of regulation in glycolysis?
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Which component is not involved in the regulation of glycolysis?
Which component is not involved in the regulation of glycolysis?
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Under what condition is anaerobic glycolysis particularly useful?
Under what condition is anaerobic glycolysis particularly useful?
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Which of the following statements about aerobic and anaerobic glycolysis is correct?
Which of the following statements about aerobic and anaerobic glycolysis is correct?
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What is the primary role of glucose transporters in cells?
What is the primary role of glucose transporters in cells?
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Which of the following best explains why aerobic glycolysis is considered more efficient than anaerobic?
Which of the following best explains why aerobic glycolysis is considered more efficient than anaerobic?
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Study Notes
Introduction to Metabolism & Glycolysis
- Metabolism is the collection of enzymatic reactions occurring in pathways.
- Enzmatic reactions are not isolated; they occur in pathways with each product becoming a substrate for the next reaction, acting like an assembly line.
- Different pathways intersect; collectively, these reactions are called metabolism.
- Catabolic pathways break down complex molecules into simpler ones.
- Anabolic pathways synthesize complex molecules from simpler ones.
- Nutrients (carbohydrates, fats, proteins) are the energy sources for metabolism.
- Complex molecules (proteins, polysaccharides, lipids, nucleic acids) are broken down to precursor molecules (amino acids, sugars, fatty acids, nitrogenous bases).
Metabolic Map
- Each pathway in metabolism is composed of multienzyme sequences.
- Each enzyme may have catalytic or regulatory features.
- Blockages in metabolic pathways can cause disorders.
Catabolic Pathways
- Functions of catabolic pathways:
- To capture ATP from energy-rich molecules.
- To convert molecules into building blocks for other components.
Stages of Catabolism
- Stage 1: Hydrolysis of complex molecules into component building blocks (proteins, carbohydrates, & fats).
- Stage 2: Conversion of building blocks into acetyl-CoA (or simple intermediates).
- Stage 3: Oxidation of acetyl-CoA and oxidative phosphorylation.
Anabolic Pathways
- Combine simple components into complex ones. For example, amino acids combine to form proteins.
- Require energy (endergonic) – often ATP, where the ATP is converted into ADP and Pi
- Often requires reducing power NADPH.
- Catabolism is a convergent process, anabolism is a divergent process.
Regulation of Metabolism
- Intracellular communication
- Intercellular communication
- Second messenger systems
- Adenylyl cyclase
- GTP-dependent regulatory proteins
- Protein kinases
- Dephosphorylation of proteins
- Hydrolysis of cAMP
- Direct contact
- Signaling cell
- Target cells
Overview of Glycolysis
- All tissues use glycolysis.
- Functions:
- Oxidize glucose to provide energy in the form of ATP.
- Provides intermediates for other metabolic pathways.
- Glycolysis is at the hub of CHO metabolism.
- Virtually all sugars are converted into glucose prior to entering glycolysis.
Aerobic and Anaerobic Glycolysis
- Aerobic glycolysis occurs in cells with mitochondria and a sufficient oxygen supply and produces pyruvate as its end product.
- Anaerobic glycolysis occurs in the absence of oxygen and converts pyruvate to lactate by oxidizing NADH to NAD+. It occurs in tissues lacking mitochondria (e.g., red blood cells) and during anoxia.
Transport of Glucose into Cells
- Facilitated diffusion (sodium-independent) is mediated by a family of glucose transporters (GLUTs) in the cell membrane (GLUT1-GLUT14).
- GLUTs have tissue specificity determined by gene expression.
- Examples of GLUTs include GLUT-1(erythrocytes, blood barrier), GLUT-2 (liver, kidney, β-cells), GLUT-3 (neurons), GLUT-4 (muscle & adipose, insulin dependent), and GLUT-5 (fructose transporter in small intestine & testes).
Sodium-Monosaccharide Cotransport
- Energy-requiring process (against concentration gradient):
- Transporter-mediated process where glucose movement is coupled to the sodium (Na+) concentration gradient.
- Called sodium-dependent glucose transporter (SGLT).
- Occurs in epithelial cells of the intestine, renal tubules, & choroid plexus.
Glucose Transport in Intestinal Epithelial Cells
- Glucose movement occurs through the different compartments of the cell.
- Active transport of Na+ coupled to glucose
- Facilitated diffusion of glucose out of the cell
Reactions of Glycolysis
- Phase 1: Energy investment phase (first 5 reactions)
- Phosphorylated intermediates formed using ATP molecules
- Phase 2: Energy generation phase (subsequent reactions)
- Net of 2 ATP formed during the substrate-level phosphorylation step.
Phosphorylation of Glucose
- Phosphorylated sugars cannot easily penetrate cellular membranes.
- Phosphorylation of glucose traps it inside the cell.
- Glucose-6-phosphate is the first step in glycolysis which is irreversible.
- Hexokinase and glucokinase are two enzymes that catalyze the phosphorylation of glucose.
- Hexokinase has broad substrate specificity, low Km, and is inhibited by its product.
- Glucokinase is found in the liver & β-cells of the pancreas. It is a glucose sensor that regulates insulin secretion.
Regulation of Glucokinase Activity by Glucokinase Regulatory Protein
- GKRP regulates the activity of glucokinase.
- In the presence of fructose-6-phosphate, GKRP binds tightly to glucokinase and inactivates it.
- When glucose concentrations increase, glucokinase is released from GKRP, permitting phosphorylation of glucose.
- Glucokinase functions as a glucose sensor in glucose homeostasis.
Isomerization of Glucose 6-Phosphate
- Catalyzed by phosphoglucose isomerase.
- Reaction is reversible
- Not a rate-limiting or regulated step
Phosphorylation of Fructose 6-phosphate
- Catalyzed by phosphofructokinase-1 (PFK-1).
- Important control point in glycolysis.
- Regulation by energy levels within the cell (inhibited by high ATP & citrate, activated by high AMP).
- Regulation by fructose 2,6-bisphosphate (potent activator of PFK-1, can override ATP inhibition).
Cleavage of Fructose 1,6-bisphosphate
- Aldolase cleaves fructose 1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate.
- Reaction is reversible and not regulated
Isomerization of Dihydroxyacetone Phosphate (DHAP)
- Triose phosphate isomerase interconverts DHAP and glyceraldehyde 3-phosphate.
Oxidation of Glyceraldehyde 3-phosphate
- First oxidation-reduction reaction in glycolysis, catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GPDH).
- NAD+ is regenerated in the cell for glycolysis through either lactate production (anaerobic glycolysis) or by respiration (aerobic glycolysis).
Synthesis of 3-phosphoglycerate, ATP Production, and Shift of Phosphate Group
- Steps in glycolysis producing ATP & phosphorylated intermediates
Dehydration of 2-phosphoglycerate
- Processes to form phosphoenolpyruvate
Formation of Pyruvate
- Catalyzed by pyruvate kinase (PK), the third irreversible step in glycolysis.
- Feedforward regulation by fructose-1,6-bisphosphate.
- Regulation by phosphorylation - the protein kinase leads to inactivation. Dephosphorylation reactivates it.
- PK deficiency relates to RBC maturation and lack of mitochondrial function.
Reduction of Pyruvate to Lactate
- Lactate dehydrogenase (LDH) catalzyes the conversion of pyruvate to lactate by reducing NAD+ to NADH
Energy Yield from Glycolysis
- Anaerobic glycolysis: 2 molecules of ATP/glucose; no net change in NADH.
- Aerobic glycolysis: 2 molecules of ATP/glucose; 2 molecules of NADH.
Hormonal Regulation of Glycolysis
- Insulin and glucagon reciprocally regulate glycolysis at 3 major control points.
- The regulatory enzymes involved are transcriptionally upregulated (insulin) or downregulated (glucagon).
- Hormonal regulation is coupled with the quick allosteric inhibition and activation, and covalent (phosphorylation/dephosphorylation) regulation.
Summary
- Key elements of glycolysis: 3 irreversible reaction steps, importance of ATP and NAD+.
Why is CHO Metabolism of Interest to You?
- Changes in cancer cells:
- Cancer cells often preferentially use anaerobic glycolysis (Warburg effect)
- Changes in glucose metabolism are implicated.
Changes in Glucose Metabolism in Cancer Cells
- Detailed molecular mechanisms involved in the change in glucose metabolism in cancer cells.
Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis
- Summary of article about fructose metabolism in colon cancer.
What You Should Know at the End of This Lecture
- Summary of key points for glycolysis in metabolism and related topics.
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Description
This quiz explores various aspects of glucose transporters and their functions, including GLUT-2, GLUT-5, and facilitated diffusion. It also examines key metabolic pathways like glycolysis, catabolism, and anabolism. Test your knowledge on how these processes contribute to glucose metabolism and energy production.