Chapter 8 - Metabolic Pathways Flashcards
What is the most common enzyme that makes use of glucose when it enters the cell?
hexokinase
What is a kinase?
an enzyme that involves the transfer of a terminal phosphate group of an ATP unit to some other compound
In glycolysis, what happens to glucose (Step 1)?
Step 1 (first investment step): glucose is converted to glucose-6-phosphate with the help of hexokinase which transfers a phosphate from ATP to the C6 position.
What is the significance of phophorylating glucose once it is inside the cell?
Adding a negative charge from the phosphate group traps glucose in the cell. It cannot pass through the cell membrane.
In glycolysis, what happens to glucose-6-phosphate?
Step 2: glucose-6-phosphate is isomerized into fructose-6-phosphate by the enzyme phosphoglucose isomerase.
*enediol intermediate
In glycolysis, what happens to fructose-6-phosphate?
Step 3 (second investment step): fructose-6-phosphate is converted to fructose-1,6-diphosphate by a transferase, phosphofructokinase, which transfers a phosphate from ATP to the C1 position.
In glycolysis, what happens to fructose-1,6-diphosphate?
Step 4: fructose-1,6-diphosphate is cleaved by a lyase, aldolase between C3 and C4 to form dihydroxyacetonephosphate (DHAP) and glyceraldehyde 3-phosphate (G3P).
*Reverse aldol condensation
In glycolysis, what happens to dihydroxyacetonephosphate (DHAP)?
Step 5: dihydroxyacetonephosphate (DHAP) is isomerized into glyceraldehyde-3-phosphate (G3P) by triose phosphate isomerase.
Describe Phase I of glycolysis (final products, what has been used)
Glucose is converted into two triose phosphates (G3P). There has been no oxidation/reduction. 2 ATP have been used.
In glycolysis, what happens to glyceraldehyde-3-phosphate (G3P)?
Step 6: glyceraldehyde-3-phosphate (G3P) is converted to 1,3-diphosphoglycerate (1,3-DPG) by glyceraldehyde-3-phosphate dehydrogenase, which uses NAD+ to oxidize the C1 position and adds a phosphate from Pi.
In glycolysis, what happens to 1,3-diphosphoglycerate?
Step 7: 1,3-diphosphoglycerate is converted to 3-phosphoglycerate by phosphoglycerate kinase, which transfers a phosphate to ADP to form ATP.
In glycolysis, what happens to 3-phosphoglycerate?
Step 8: 3-phosphoglycerate is converted to 2-phosphoglycerate by phosphoglyceromutase, which exchanges the current phosphate for a phosphate on the enzyme.
In glycolysis, what happens to 2-phosphoglycerate? What is a side reaction?
Step 9: 2-phosphoglycerate is converted to phosphoenolpyruvate (PEP) by enolase.
*2-phosphoglycerate can also be converted to 2,3-bisphosphoglycerate (2,3-BPG) by 2,3-BPG phosphatase.
In glycolysis, what happens to phosphoenolpyruvate (PEP)?
Step 10: phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase, which transfers a phosphate group to ADP to form ATP.
In which ways can NAD+/FAD be regenerated after glycolysis?
Anaerobic conditions: pyruvate can be converted to lactate by lactace dehydrogenase, which uses NADH to reduce pyruvate, forming NAD+.
Yeasts (alcoholic fermentation): pyruvate can be converted to acetaldehyde by the lyase, pyruvate decarboxylase and then to ethanol by alcohol dehydrogenase, which uses NADH to reduce acetaldehyde, forming NAD+.
*Aerobic conditions: pyruvate is oxidized to carbon dioxide through the Krebs cycle, producing more NADH and FADH2. Those lost electrons are eventually shuttled to oxygen on the electron transport chain, regenerating NAD+ and FAD.
What is the most important regulatory step in glycolysis? What are 3 examples of inhibition at this step?
Regulation is important at step 3. Phosphofructokinase is inhibited by high levels of ATP, H+ (from formation of lactate), and citrate (Krebs cycle). These signifiy that glucose is being used well, and shouldn’t be wasted.
What hydrolytic enzymes break down disaccharides in the small intestine?
maltase, sucrase, and lactase (sometimes)
How can monosaccharides other than glucose be used for glycolysis?
They must be converted to an intermediate in the glycolytic pathway.
Where does glycolysis occur in the cell?
cytosol
Where does the Krebs/citric acid cycle occur in the cell?
mitochondrial matrix
What is the first major reaction pyruvate undergoes in its journey to the Krebs cycle?
Pyruvate is decarboxylated by a pyruvate dehydrogenase complex (3 enzymes) to form acetyl-coenzyme A and carbon dioxide. This step is accompanied by NAD+ which reduces to NADH.
How is acetyl coenzyme A introduced to the Krebs cycle?
It is undergoes an aldol condensation and hydrolysis with oxaloacetic acid to form citrate and releases coenzyme A. The lyase, citrate synthetase carries out this reaction.
What is the unique functional group in acetyl-coenzyme A and succinyl-coenzyme A?
They have a high energy thioester bond.
What is a lyase?
an enzyme that catalyzes the breaking of bonds by means other than hydrolysis and oxidation, often forming a new double bond or ring structure
In the Krebs cycle, what happens to citrate?
Citrate loses its hydroxyl group with the help of aconitase, forming a tertiarty carbonium ion intermediate. An elimination reaction makes cis-Aconitate than can then be hydrolyzed with the help of aconitase to form isocitrate.
In the Krebs cycle, what happens to isocitrate?
Isocitrate is oxidized by NAD+ with isocitrate dehydrogenase to form a β-keto acid that is very unstable, with the release of NADH. It decarboxylates, forming α-ketoglutarate (α-KG) and releases carbon dioxide.
In the Krebs cycle, what happens to α-ketoglutarate?
α-ketoglutarate will be oxidized by NAD+ with the help of an α-Ketoglutarate Dehydrogenase Complex, forming succinyl-coenzyme A, with the release of NADH and carbon dioxide.
In the Krebs cycle, what happens to succinyl-coenzyme A?
Succinyl-coenzyme A is converted to succinate by a ligase, succinyl-coA synthetase, which uses the water produced from the synthesis of GTP from GDP and Pi to hydrolyze the thioester bond. GTP and coenzyme A are released.
What is a ligase?
an enzyme that puts two molecules together using a high energy phosphate bond
In the Krebs cycle, what happens to succinate?
Succinate is oxidized to fumerate by FAD, with the help of succinate dehydrogenase.
In metabolism, NAD normally converts what to what?
It normally oxidized alcohols to ketones/aldehydes.
In metabolism, FAD normally converts what to what?
It typically oxidizes alkanes to alkenes.
In the Krebs cycle, what happens to fumarate?
Fumarate reacts with water to produce malate, with the help of a lyase, fumarase.
In the Krebs cycle, what happens to malate?
Malate is oxidized to oxaloacetic acid by NAD+ with the help of malate dehydrogenase.
In the Krebs cycle, what happens to oxaloacetic acid?
Oxaloacetic acid undergoes an aldol condensation and hydrolysis with acetyl-coenzyme A to form citrate, with the help of a lyase, citrate synthetase. Coenzyme A is released.
What is the “potential energy” generated in the Krebs cycle?
Many reduced coenzymes (FADH2 and NADH) have been made, which can later be oxidized by oxygen to liberate a lot of energy.
Is the Krebs cycle catabolic or anabolic? Why?
It is catabolic because acetyl coenzyme A is broken down to release 2 of its carbons in the form of carbon dioxide.
Describe the thermodynamics of the Krebs cycle
It has a favorable, negative ΔGº because carbon dioxide is released as a gas. It is very difficult to harness that for the reverse process.