Module 7 - Metabolism Flashcards
Explain the difference between anabolic and catabolic processes.
Catabolism is a set of the metabolic pathway that breaks down the molecule into smaller units releasing energy.
Anabolism is a set of the metabolic pathway that construct molecules from smaller units using energy in the process.
Mention an example of passive transport by an integral membrane protein.
GLUT1 glucose transporter
Describe the model for conformational change allows GLUT 1 to able to translocate glucose across membranes.
The transporter model is made up of 4 amphipathic helices (helix 1, 4, 7, 10) with a central polar region allowing glucose to pass through. GLUT1 exists in 2 conformations (T1 and T2).
The binding of glucose with the T1 structure induces thermal energy that induces a conformational change from T1 to T2. T2 structure opens up the GLUT1, allowing passage of glucose inside the cell, before reverting back to T1.
Rationalize the kinetic properties of GLUT family transporters with their tissue distribution and functional role.
If the Kt is larger than the glucose concentration level, the rate of glucose uptake will be slow and vice versa.
State the Warburg hypothesis and explain how this has influenced chemotherapeutic treatments for cancer.
The hypothesis proposes that most cancer cells produce energy by anaerobic glycolysis rather than oxidative of pyruvate.
Hence, chemotherapeutic treatments for cancer may involve applying glycolysis inhibitors (such as 2-deoxyglucose, a Hexokinase inhibitor).
Compare Gluconeogenesis and Glycolysis highlighting the differences in subcellular location, substrate(s), cofactor(s), product(s) and enzymes used.
The 3 irreversible steps of glycolysis are catalyzed by different enzymes in GNG.
- Conversion of pyruvate to phosphoenolpyruvate (PEP) is catalysed by the mitochondrial pyruvate carboxylase and the cytosolic PEP carboxykinase. Biotin is the cofactor (vitamin B7) used. GTP is used as a source of Pi and leads to the release of GDP and CO2.
- Conversion of fructose-1,6-biphosphate to fructose-6-phosphate catalysed by fructose-1,6-bisphosphatase in the cytosol.
- Conversion of glucose-6-phosphate to glucose is catalysed by G6Pase in the ER lumen of liver and kidney cortex.
Explain why is lactate dehydrogenase important during anaerobic glycolysis.
Lactate dehydrogenase regenerates the NAD+ for the anaerobic glycolysis (oxidation of G3P)
Describe the metabolic fate of lactate produced in the muscle and how this is linked to metabolism in the liver.
Lactate produced in the muscle will be transported through the blood to the liver, where through the process of GNG it is processed back to glucose where it can be stored as glycogen back in the muscle as energy storage. This cycle is called the Cori Cycle.
Describe the structure of glycogen; and why it is stored in the liver and muscle.
Glycogen is a polysaccharide comprised of alpha-D-glucose units linked via alpha-1,4 glyosidic bonds with branching points with an alpha-1,6.
It is a storage form of carbohydrate in the body. In the liver, glycogen can be a source of blood glucose. While in muscle, glycogen can power muscle contraction.
Explain how glycogenolysis and glycogenesis are linked to glycolysis and gluconeogenesis.
Glycogenolysis involves the following enzymes:
- Glycogen phosphorylase: cleavage of glucose from the non-reducing end of the glycogen chain to form G1P
- Debranching enzyme: transfer a block of 3 glucose residues to a nearby non-reducing end & hydrolize the alpha 1->6 linkages to free the glucose
- Phosphoglucomutase: conversion of G1P to G6P (able to be used for GNG and Glycolysis
Glycogenesis involves the following enzymes;
- UDP-GLucose Phosphorylase: produces UDP-glucose from UTP and G1P
- Glycogen Synthase: adds glucose to the glycogen chain from the UDP-glucose
- Glycogen Branching Enzyme: catalyzes the transfer of a block of 6 or 7 glucose residues from the nonreducing end of a glycogen branch having at least 11 glucose residues
- Glycogenin: primer for new chains to assemble form glucose
Rationalize the changes in metabolism that arise due to enzyme deficiencies that cause glycogen storage diseases.
Compare the function of Complex I, II, III and IV from the Electron Transport Chain.
- Complex I: transfer of electrons from NADH to Coenzyme Q (becomes QH2) as well as pumping H+ to intermembrane space (concurrent)
- Complex II: transfer of electron from FADH2 to Coenzyme Q
- Complex III: transfer of electrons from QH2 to Cytochrome C as well as acting as proton pump
- Complex IV: receives electron from Cyt C and oxygen acts as final oxygen receptor forming water, acts as proton pump
Describe how the Electron Transport Chain is linked to the Krebs Cycle.
Complex II is also known as succinate dehydrogenate which facilitates the conversion of succinate to fumarate, which produces FADH2, which is an electron carrier used in the ETC.
Explain the Chemiosmotic Model.
Oxidative phosphorylation is defined as the process of transforming redox energy formed under aerobic conditions during Glycolysis and the Citric Acid Cycle (i.e. NADH and FADH2) into chemical energy in the form of ATP.
In effect, redox energy is converted to an electrochemical gradient which drives the unfavourable formation of ATP
Explain the function of ATP Synthase, including a description of the mechanism for synthesizing ATP using the proton gradient generated from the electron transport chain.
F1 component has 3 nonequivalent adenine nucleotide-binding site, one for each of the α/β pair. The sites are either in the:
- β-ATP conformation
- β-ADP conformation (binding of ADP with Pi)
- β-empty
The proton motive force, induced by the H+ being pumped through the F0 component, causes the rotation of the γ subunit. This rotation mediates the continual conformation change of the binding site, producing ATP from ADP and Pi.
Calculate the different number of ATP produced per NADH and FADH2 that enter the electron transport chain.
Describe the structure of the ATP synthase in terms of the subunits that make up the FO and F1 components and whether subunits rotate or a fixed.
ATP synthase is comprised of an FO (stalk) and F1 (head) component.
Fo spans the inner mitochondrial membrane and is comprised of the a, b, and c subunit in mammals which are fixed.
F1 is located on the matrix and is composed of α, ß, y, δ, ε subunits, which are rotatable.
How are phosphate and ADP supplied to the matrix in the formation of ATP?
Reaction 1 of the Preparatory Phase of Glycolysis.
Reaction 2 of the Preparatory Phase of Glycolysis.
Reaction 3 of the Preparatory Phase of Glycolysis.
Reaction 4 of the Preparatory Phase of Glycolysis.
Reaction 5 of the Preparatory Phase of Glycolysis.
Reaction 6 of Glycolysis (Payoff Phase)
Reaction 7 of Glycolysis (Payoff Phase)
Reaction 8 of Glycolysis (Payoff Phase)
Reaction 9 of Glycolysis (Payoff Phase)
Reaction 10 of Glycolysis (Payoff Phase)
Step from Pyruvate to PEP (GNG)
Step from F-1,6-bP to F-6-P (GNG).
Step from G-6-P to Glucose (GNG)
Lactic acid Fermentation
Alcohol Fermentation.
Step from Pyruvate to Acetyl CoA
Reaction 1 of Kreb’s Cycle
Reaction 2 of Kreb’s Cycle
Reaction 3 of Kreb’s Cycle
Reaction 4 of Kreb’s Cycle
Reaction 5 of Kreb’s Cycle
Reaction 6 of Kreb’s Cycle
Reaction 7 of Kreb’s Cycle
Reaction 8 of Kreb’s Cycle
