Test 3 biochemrename
evan406's version from 2016-04-22 03:06
|Glycogen||glucose units linked by (α1→4) glycosidic bonds. |
α linkages cause bends in the chain making helical structures
cannot form long fibers, is highly branched and, very water-soluble.
storage fuel in animals.
abundance of free, nonreducing ends, can be hydrolyzed to release glucose 1-phosphate, available for oxidation and energy production.
|cellulose||glucose units linked by (β1→4) glycosidic bonds. |
β linkages force polymer chain into an extended conformation.
Parallel series of extended chains aggregate into long, tough, insoluble fibers.
Cellulose serves as a structural material in plants
|Glycosaminoglycans||long unbranched polysaccharides consisting of a repeating disaccharide unit. |
repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine.
chains may be covalently linked to a protein to form proteoglycans.
chains are sulfonated and highly charged.
|Describe in detail how the sugar code is used to direct white blood cells to sites of inflammation.||Leukocytes roll along the vascular wall. This rolling movement is mediated by reversible adhesive interactions via selectins (glycoproteins) and selectin receptors (lectins). |
L-selectins are present on the leukocyte and are important for the rolling. P-selectins are present on the endothelial cell.
P-selectins are transported to the cell membrane after exposure to inflammatory signal molecules. P-selectins bind stronger to the leukocyte, causing the leukocyte to slow down and to enter the wall.
Inflamed tissues have increased amounts of sialylated and fucosylated epitopes on the cell surface, often in sulphated form. L-selectins present on the white blood cells bind to these sugar units.
|What is the sugar code and explain how it is involved in protein targeting||Cells use specific oligosaccharides to encode important information about intracellular targeting of proteins, cell-cell interaction, tissue development and extracellular signals. Lectins play an important role by recognizing and binding to the different oligosaccharides.|
The sugar code plays an important role in the targeting of for example hydrolase:
- The hydrolase protein contains a signal sequence that is recognized by the SRP particle and as a result the enzyme is guided into the ER during synthesis
- In the ER the lysozyme is glycosylated
- Lysosomal enzymes contain a signal patch that is recognized by an enzyme that phophorylates a mannose residue at the terminus of an oligosaccharide chain
- This residue is recognized by a special receptor (or lectin)
- When a section of the Golgi complex containing this receptor buds off to form a transport vesicle, proteins containing mannose phosphate residues are dragged into the forming bud by interaction of their mannose phosphates with the receptor; the vesicle then moves to and fuses with a lysosome, depositing its cargo therein.
|Synthesis of glycogen||Glycogen synthesis start with the activation of glucose to UDP-glucose, catalyzed by UDP-glucose pyrophosphorylase.|
Glycogen synthase uses UDP-glucose as a substrate and adds the glucose units to the growing glycogen chains.
Branches are introduced by the enzyme amylo(1,4→1,6)-transglycosylase (branching enzyme).
The enzyme transfers a six- or seven-residue segments of a growing glycogen chain to the C-6 hydroxyl group of a glucose residue on the same or a nearby chain.
|breakdown of glycogen||Glycogen breakdown starts with the enzyme glycogen phosphorylase which cleaves glucose from the nonreducing ends of glycogen molecules and forms glucose-1- phosphate. |
It can only do that with the long chain and leaves limit dextrans behind that have to be broken down by the debranching enzyme.
In the first step a trisaccharide group from a limit branch is transferred to the end of a nearby branch. (oligo(α1,4→α1,4) glucanotransferase activity)
The remaining single glucose unit from the branch is subsequently cut off (α(1→6) glucosidase activity).
The glucose-1-phosphate produced is converted into glucose-6-phosphate by phosphoglucomutase.
|What are anabolic and catabolic pathways. Explain their differences and their roles in detail.||Catabolism is the degradative phase of metabolism in which organic molecules are converted into smaller, simpler end products. Catabolic pathways release energy.|
In anabolism small, simple precursors are built up into larger and more complex molecules. Anabolic reactions require an input of energy.
|Normally it takes energy to break a covalent bond. The hydrolysis of ATP, however, has a large negative ΔG°’ value. List and explain the five reasons why this is the case.||1) The charge separation that results from hydrolysis relieves electrostatic repulsion among the four negative charges on ATP. |
2) The product Pi is stabilized by formation of a resonance hybrid
3) The product ADP2- immediately ionizes, releasing a proton into a medium of very low [H+] increasing the entropy of the solution
4) The ΔG’° value is highly dependent on concentration of ATP, ADP, Pi, and Mg2+. Deviation from standard condition causes the value of ΔG’° to be more negative.
5) A greater degree of solvation of the products Pi and ADP relative to ATP further stabilizes the products relative to the reactants.
|Indicate the steps that are different in glycolysis and gluconeogenesis. Explain why only these steps are different and not any of the other steps.||Three steps of the glycolytic pathway are different:|
1) conversion of glucose into glucose 6-phosphate
2) conversion of fructose 6-phosphate into fructose 1,6-bisphosphate
3) conversion of phosphoenolpyruvate into pyruvate
Glycolysis is exergonic mainly due to these three irreversible steps.
In gluconeogenesis these three steps have to be catalyzed by other enzymes.
In glycolysis an ATP is consumed in step 1 and in step 2. To make the reverse process energetically favorable the reaction are uncouple from ATP synthesis and a single Pi is released instead.
In step 3 in glycolysis an ATP is produced. To make the reverse step possible an ATP and a GTP are hydrolysed to put in additional energy and make the step energetically favorable in the opposite direction.
|What is the physiological rationale behind coordinated activation of gluconeogenesis and glycogen breakdown in the liver, vs. coordination of glycolysis and glycogen breakdown in muscle?||The rational is to get glucose to the muscles for the production of ATP in glycolysis, the TCA cycle, and oxidative phosphorylation. |
In the liver glucose is produced via gluconeogenesis and the glycogen storage is broken down to form glucose. This enters the blood stream and is taken up by the muscles. There the glucose is released from glycogen too. All this glucose enters glucolysis.
|What are the hormones and enzymes central to gluconeogenesis and glycolysis?||Both Glucagon and Epinephrine are the start signals. Binding to the cell receptors causes a cAMP dependent signaling cascade resulting in phophorylation PFK-2/F-2,6-BPase. The liver PFK-2 is inhibited, while the F-2,6- BPase is activated. This result in the removal of fructose-2,6-bisphosphate. This causes and inactivation of PFK-1 and inhibition of glycolysis and activation of F-1,6-BPase and activation of gluconeogenesis.|
The muscle PFK-2 is activated while the F-2,6-BPase is inhibited by the phosphorylation. There will be an increase in the concentration of fructose-2,6- bisphosphate. This causes and activation of PFK-1 and activation of glycolysis and inactivation of F-1,6-BPase and inhibition of gluconeogenesis.
(+)catalization and (-)inhibition of regulatory steps in glycolysis/gluconegenesis
|phosphofructokinase||+ fructose-2,6-bisphosphate/AMP |
|pyruvate kinase||+ fructose-1,6-BP|
- acetyl CoA/ATP/alanine
- cAMP dept. regulation
|pyruvate carboxylase||+ acetyl-CoA|
|fructose-1,6-bisphosphatase:||- fructose-2,6-BP/AMP |
|glycogen synthase:||+ insulin|
|glycogen phosphorylase||+ cAMP dept. regulation/ phosphorylation/glucagon/epinephrine |
|glucose-6-phosphate dehydrogenase||- NADPH|
|Allosteric inhibition, for example the effect of ATP on phosphofructokinase-1, has a different effect on the Michaelis-Menten plot than for example a reversible inhibitor. Explain how these two effects can be distinguished in a kinetic experiment.||Regular, reversible inhibitors will not change the hyperbolic character of the curve.|
With an allosteric inhibitor, however, the hyperbolic curve becomes a sigmoid.
|The figure shows an overview of the different pathways glucose is involved in. Indicate in the figure which of these steps are regulated (9 total), give the enzyme names that catalyze these step and indicate the compounds that are involved in the regulation|
 pyruvate kinase:
- acetyl CoA/ATP/alanine
- cAMP dept. regulation
 pyruvate carboxylase:
 glycogen synthase:
 glycogen phosphorylase:
+ CAMP dept. regulation/ phosphorylation/glucagon/epinephrine
 glucose-6-phosphate dehydrogenase:
|Explain how NADH is recycled to NAD+ under aerobic conditions and under anaerobic conditions. Why is it important to recycle NADH produced during glycolysis to NAD+?||Cells contain a limited supply of NAD+ and NADH. The oxidation of glyceraldehyde 3- phosphate requires NAD+ as an electron acceptor—it converts NAD+ to NADH. Unless this NADH is recycled to NAD+, oxidative metabolism in this cell will cease for lack of an electron acceptor. Under aerobic conditions, NADH passes electrons to O2; under anaerobic conditions, NADH reduces pyruvate to lactate, and is thereby recycled to NAD+.|
|The enzyme pyruvate decarboxylase plays an important role in fermentation. Draw the first two steps in the reaction mechanism and explain the role of the cofactor thiamine pyrophosphate.||A C-C bond is broken and a carbanion is formed that is highly unstable. The initial binding of TPP to the substrate provides can alternative pathway where the electron density that is formed is stabilized.|
1) Nucleophilic attack by the ylid form of TPP on the carbonyl carbon of pyruvate to form a covalent adduct
2) Departure of CO2 to generate a resonance-stabilized carbanion adduct in which the thiazolium
|Explain the role and the importance of the Shiff base formation in the aldolase reaction. Your answer should include drawing the first couple of steps of the reaction mechanism that lead up to the formation of the Schiff base and the resulting stabilization of the reaction intermediates.||Heterolytic breakage of the C-C bond causes the formation of a carbanion. This has to be stabilized. The formation of the Shiff base allows the movement of the formed electron density towards the nitrogen atom that function as an electron sink.|
|Describe in detail how the bifunctional enzyme phosphofructokinase-2/fructose-2,6- bisphophatase and the product fructose-2,6-bisphosphate regulate glycolysis and gluconeogenesis.||- Fructose-6-phosphate activates PFK-2 and inhibits F-2,6-BPase|
- The production of F-2,6-BP stimulates glycolysis by allosteric activation of PFK-1 and inhibits gluconeogenesis by allosteric inhibition of F-2,6-BPase
- Phosphorylation by cAMP-dependent protein kinase inhibits PFK-2 activity and stimulates F-2,6-BPase activity
|Describe the process by which "old" serum glycoproteins are removed from the mammalian circulatory system.||Newly synthesized serum glycoproteins bear oligosaccharide chains that end in sialic acid. |
the sialic acid is removed with time.
Glycoproteins that lack the terminal sialic acid are recognized by receptors in the liver, internalized, and destroyed.
|What is gluconeogenesis, and what useful purposes does it serve in people?||Gluconeogenesis is the biosynthesis of glucose from simpler, noncarbohydrate precursors such as oxaloacetate or pyruvate. During periods of fasting, when carbohydrate reserves have been exhausted, gluconeogenesis provides glucose for metabolism in tissues (brain, erythrocytes) that derive their energy primarily from glucose metabolism.|