Chapter 9: Carbohydrate Metabolism I: Glycolysis, Glycogen, Gluconeogenesis, Pentose Phosphate Pathway Flashcards

Question

What is Phosphofructokinase I? What is special about it? What is it inhibited by (3 things) and activated by?

Answer 1

PFK-I is the rate limiting enzyme of glycolysis. The process is also irreversible. PFK-1 is the main control point in glycolysis. PFK-1 phosphorylates fructose 6-P to fructose 1,6 bisP, using ATP. PFK-1 is inhibited by ATP, citrate, glucagon. and activated by AMP: turns off glycolysis when it has sufficient energy in ATP, and turn on glycolysis when it needs energy (high AMP). (High levels of citrate indicate that the cell is producing sufficient energy as citrate is an intermediate of the citric acid cycle).

Answer 2

PFK II is an enzyme in the glycolytic pathway which coverts a small amount of fructose 6-P to fructose 2,6-P, which activates PFK I. Insulin stimulates PFK II. PFK2 is found in the liver. Glucagon, a hormone produced by the pancreas that plays a crucial role in regulating blood sugar levels, inhibits PFK I in hepatocytes.

Answer 3

*Glucagon inhibits PFK I in liver cells by an indirect mechanism involving PFK II and fructose 2,6 bisP, as shown in the image. So. Insulin activates PFK2. PFK2 converts F6P to F26BP, F26BP activates PFK1. *Glucagon inhibits PFK2, lowers F26BP and thereby inhibiting PFK1. Activating PFK1 allows cells to override ATP inhibition of PFK1 so that glycolysis can continue even when cells have plenty of energy. THE REASON THIS HAPPENS IS BECAUSE THE METABOLITES OF GLYCOLYSIS CAN BE FED INTO PRODUCTION OF GLYCOGEN, FATTY ACIDS, AND OTHER STORAGE MOLECUKES RATHER THAN BEING BURNED TO PRODUCE ATP.

Answer 4

Glycolysis, the breakdown of glucose, produces two molecules of pyruvate, two molecules of ATP (with a net gain of 2 ATP), and two molecules of NADH.

Answer 5

Glyceraldehyde 3P dehydrogenase catalyzes and oxidation and addition of an organic P to glyceraldehyde 3P. This is important because it creates a high energy intermediate, 1,3 bisPglycerate and the reduction of NAD+ to NADH. If glycolysis is aerobic, NADH can be utilized in the mitochondrial ETC to provide energy to synthesize ATP via oxidative phosphorylation.

Answer 6

3Pglycerate kinase forms ATP and 3phosphoglycerate by transferring highE P from 1,3bPglycerate to ADP.

Answer 7

The last enzyme in glycolysis. Catalyzes a substrate level phosphorylation of ADP. It produces ATP and pyruvate. It transfers a high every P from phosphenolpyruvate (PEP) to ADP. F1,6bP (from PFK1) activates pyruvate kinase. This is interesting because it is a FEED FORWARD ACTIVATION.

Answer 8

Pyruvate kinase is activated by F1,6bP, feed forward activation.

Answer 9

PFK1: glycolysis, the rate limiting enzyme and is also irreversible. Lactate dehydrogenase: fermentation enzyme, oxidizes NADH to NAD+.

Answer 10

In the absence of oxygen, lactate dehydrogenase will oxidize NADH to NAD+. This replenishes NAD+ in the absence of oxygen. This is then used to allow glycolysis to continue. There is no net loss of carbon because pyruvate and lactate are both 3 carbon molecules. A little more: Without the mitochondria and oxygen, glycolysis would stop when all of the available NAD+ has been reduced to NADH. By reducing pyruvate to lactate, and oxidizing NADH to NAD+ (using lactate dehydrogenase), the problem of not having NAD+ in the absence of oxygen is temporarily solved.

Answer 11

DHAP, dihydroxyacetone phosphate, a precursor to tracylglycerol synthesis. Used in hepatic and adipose tissue. 1,3bPglycerate and phosphoenolpyruvate (PEP) are high E intermediates used to generate ATP by substrate level phosphorylation.

Answer 12

Glucokinase and hexokinase PFK1 Pyruvate Kinase

Answer 13

High 2,3 BPG Low pH High [H+] High pCO2 These all occur during exercise. Exercise is the Right thing to do; the oxygen dissociation curve shifts to the Right during exercise.

Answer 14

Increased respiration Increase oxygen affinity for hemoglobin (initial) Increase rate of glycolysis Increased 2,3 BPG in RBC (over 12-24 hour period) Normalized oxygen affinity for hemoglobin restored by increase levels of 2,3 BPG Increase hemoglobin (over days to weeks)

Answer 15

Anaerobic glycolysis is the only pathway for ATP production in RBC. 2 ATP per glucose. 4 ATP gross but 2 are used in the process.

Answer 16

Bisphosphoglycerate mutate is the enzyme in RBC used for anaerobic glycolysis. Bisphosphoglycerate produces 2,3 BPG from 1,3 BPG. Recall that MUTASES are enzymes that move functional groups from one place on a molecule to another place on a molecule. In this case, the phosphate is moved from the 1 position to the 2 position.

Answer 17

A mutase is an enzyme that moves a functional group on a molecule.

Answer 18

2,3 BPG binds allosterically to the beta chains of hemoglobin A and decreases its affinity for oxygen. This is seen in the oxygen dissociation curve of hemoglobin (HbA). The right shift is sufficient to allow unloading of oxygen at tissues, but still allows 100 saturation in the lungs.

Answer 19

An abnormal increase in erythrocyte 2,3 BPG might shift the oxygen dissociation curve far enough to the right that HbA is not fully saturated in the lungs.

Answer 20

Hexokinase phosphorylates glucose to G6P, trapping glucose in the cell. It is inhibited by G6P and is irreversible.

Answer 21

Glucokinase phosphorylates glucose to G6P and traps glucose in the LIVER and PANCREAS cells. Glucokinase works with GLUT2 as part of the glucose sensor in beta islets cells. In liver cells, it is induced by insulin. It is irreversible.

Answer 22

PFK1 catalyzes the rate limiting step of glycolysis and is irreversible. PFK1 phosphorylates F6P to F16bP using ATP. PFK1 is inhibited ATP, citrate, and glucagon. PFK1 is activated by AMP, F2,6bP, and insulin.

Answer 23

Glyceraldehyde 3P dehydrogenase generates NADH while phosphorylating glyceraldehyde 3P to glyceraldehyde 1,3 bPglycerate. Glyceraldehyde 3P is reversible.

Answer 24

3P glycerate kinase performs a substrate level phosphorylation. 3P glycerate kinase transfers a P from 1,3bPglycerate to ADP, forming ATP and 3Pglycerate. It is reversible.

Answer 25

Pyruvate kinase performs a substrate level phosphorylation. Pyruvate kinase transfers a P from phosphoenolpyruvate (PEP) to ADP, forming ATP and Pyruvate. Pyruvate kinase is activated by F1,6bP. Pyruvate kinase is irreversible.

Answer 26

Fermentation must occur to oxidize NADH to NAD+, which is in limited supply in cells. Fermentation generates no ATP or energy carriers, it merely regenerates the coenzymes needed for glycolysis.

Answer 27

The binding of 2,3BPG decreases oxygen affinity for oxygen. Fetal hemoglobin must be able to take oxygen from maternal hemoglobin at the placental interface. Therefor it would be disadvantageous to lower fetal hemoglobins affinity for oxygen.

Answer 28

Galactose and fructose can contribute to ATP production by feeding into glycolysis or other metabolic processes.

Answer 29

A big source of galactose in the diet is the disaccharide lactose, present in milk. Lactose is hydrolyzed to galactose and glucose by lactase (a brush border enzyme of the duodenum). Galactose reaches the liver through the hepatic portal vein. Galactose is phosphorated by galactokinase, trapping it in the cell similar to what happens to glucose when it is phosphorylated. Galactose one phosphate is converted to glucose one phosphate by galactose one phosphate uridyltranferase, an epimerase.

Answer 30

Lactose is a disaccharide of galactose and glucose. Lactase hydrolyzes lactose to galactose and glucose. Lactase is a brush border enzyme found in the duodenum.

Answer 31

Galactokinase: phosphorylates galactose, trapping it in the cell. Galactose 1P uridyltranserase: an epimerase that converts galactose1P to glucose1P.

Answer 32

Fructose is found in honey and fruit. Sucrose is a disaccharide, composed of fructose and glucose, that is found in honey and fruit. Sucrose is hydrolyzed by the duodenal brush border enzyme sucrase, resulting in glucose and fructose. Glucose and fructose are absorbed into the hepatic portal vein. The liver phosphorylates fructose using fructokinase, trapping it in the cell. The resulting fructose1P is cleaved into glyceraldehyde and dihydroxyacetoneP (DHAP) by aldolase B.

Answer 33

Glactokinase phosphorylates galactose and traps it in the cell. Galactose 1 phosphate uridyltransferase produces glucose1P, a glycolic intermediate, linking the metabolic pathways.

Answer 34

Frictokinase phosphorylates fructose to fructose 1P, trapping it in the cell. Aldolase B cleaves fructose 1P into glyceraldehyde (can be phosphorylated to glyceraldehyde 3P) and DHAP (dihydroxyacetone phosphate). Both products are glycolytic intermediates.

Answer 35

Acetyl coA is a coenzyme made from pyruvate (product of aerobic glycolysis) which is a precursor for the citric acid cycle and fatty acid synthesis. Acetyl coA will go to the citric acid cycle if ATP is needed. Acetyl coA will go synthesize fatty acids if there is sufficient ATP.

Answer 36

Pyruvate dehydrogenase is found in mitochondrial matrix. Pyruvate dehydrogenase in the liver is activated by insulin. This makes sense because high insulin means well fed and the liver should not only burn glucose, but it could shift the fatty acid equilibrium toward production and storage. The pyruvate dehydrogenase complex is not reversible. It cannot be used to convert acetyl coA back to pyruvate or glucose.

Answer 37

The pyruvate dehydrogenase complex is not reversible. It cannot be used to convert acetyl coA back to pyruvate or glucose.

Answer 38

Conversion to acetyl CoA by PDH (pyruvate dehydrogenase complex) Conversion to lactate by lactate dehydrogenase (NAD+ and NADH) Conversion to oxaloacetate by pyruvate carboxylase.

Answer 39

Thiamine pyrophosphate Lipoid acid CoA FAD NAD+

Answer 40

Pyruvate dehydrogenase is inhibited by its product: acetyl CoA. The buildup of acetyl CoA causes a shift in metabolism: pyruvate is no longer converted to acetyl CoA but rather into oxaloacetate (to enter gluconeogenesis).

Answer 41

Reactants: pyruvate, NAD+, CoA Products: Acetyl CoA, NADH, and CO2

Answer 42

Acetyl CoA inhibits the PDH complex. As a product of the enzyme complex, a buildup of acetyl CoA from either the citric acid cycle or fatty acid oxidation signals that the cell is energetically satisfied and that the production of acetyl CoA should be slowed or stopped. Pyruvate can then be used to form other products, such as oxaloacetate for use in gluconeogenesis.

Answer 43

Glycogen is a branched polymer of glucose and is used to store glucose.

Answer 44

Glycogen in the liver is broken down to maintain constant levels of glucose in the blood. Glycogen in muscles is broken down to provide glucose during exercise.

Answer 45

In the cytoplasm of liver and skeletal muscle cells. Stored as granules.

Answer 46

Glycogen is stored in the cytoplasm as granules. Each granule has a central protein core with polyglucose chains radiating outward to form a sphere.

Answer 47

Branched chains: density is highest at the periphery of the granule allowing more rapid release of glucose on demand. Linear chains: higher density of glucose near the core of the granule.

Answer 48

Glycogenesis is the synthesis of glycogen granules. The core protein of a glycogen granule is called glycogenin. Glucose 6P to glucose 1P to UDP glucose to glycogen.

Answer 49

Glycogen synthase is the rate limiting enzyme of glycogen synthesis. Glycogen synthase forms the alpha 1,4 glycosidic bonds found in linear chains of glucose of the granule. Glycogen synthase is stimulated by glucose 6P and insulin. Glycogen synthase is inhibited by epinephrine and glucagon.

Answer 50

Branching enzyme introduces branching of a glycogen molecule by introducing alpha 1,6 linked branches into the granule as it grows.

Answer 51

Glycogenolysis is breaking down glycogen. The main enzyme of glycogenolysis is glycogen phosphorylase. Glycogen phosphorylase breaks alpha 1,4 glucosidic bonds, releasing glucose 1P from the periphery of a granule.

Answer 52

Phosphorylase breaks binds using inorganic phosphate. Hydrolase breaks binds using water.

Answer 53

Glycogen phosphorylase breaks alpha 1,4 glucosidic bonds, releasing glucose 1P from the periphery of a granule. Glycogen phosphorylase is activated by glucagon in the liver. Glycogen phosphorylase is activated by AMP and epinephrine in the muscle, which signals that the muscle needs more glucose. Inhibited by ATP.

Answer 54

Debranching enzyme is a complex of two enzymes thus deconstructs the branches of glycogen. The linear binds are alpha 1-4, the branching are alpha 1,6. These areas require different enzymes to phosohrylase and hydrolyze.

Answer 55

Isoforms are slightly different versions of the same protein. In the case of glycogen enzymes, there are ten different isoforms of the enzymes in the liver and muscle. Deficiencies are termed glycogen storage diseases because all are characterized by accumulation or lack of glycogen in one or more tissues.

Answer 56

Glycogen is made up of a core protein of glycogenin with linear chains of glucose emanating out from the center connected by alpha 1,4 glucosidic linkage. Branched chains require alpha 1,6 glucosidic linkage.

Answer 57

Glycogen synthase attached the glucose molecule from UDP-glucose to the growing glycogen chain, forming an alpha 1,4 link. Branching enzyme creates a branch by breaking an alpha 1,4 link in the growing chain and moving a block of oligoglucose to another location in the glycogen granule. The oligoglucose is then attached with an alpha 1,6 link.

Answer 58

Glycogen phosphorylase removes a glucose molecule from glycogen using a phosphate, breaking the alpha 1,4 link and creating a glucose 1P. Debranching enzyme moves all of the glucose from a branch to a longer glycogen chain by breaking an alpha 1,4 link and forming a new alpha 1,4 link to the longer chain. The branch point is left behind, which is removed by breaking the alpha 1,6 link to form a free molecule of glucose.

Answer 59

The liver in the blood during fasting through either glycogenolysis or gluconeogenesis. The kidney also does this to a lesser extent. Gluconeogenesis is promoted by glucagon and epinephrine, which act to raise blood sugar levels. Gluconeogenesis is inhibited by insulin, which acts to lower blood sugar level levels. Glycerol 3P (from stored fats, or triglycerides, in adipose tissues) Lactate (from anaerobic glycolysis) Glucogenic amino acids (from muscle proteins).

Answer 60

During fasting, glycogen reserves dropped dramatically in the first 12 hours. During which time gluconeogenesis increases. After 24 hours, gluconeogenesis represents the sole source of glucose.

Answer 61

All AA expect luecine and lysine (which are ketogenic) can be converted into intermediates that feed into gluconeogenesis. The other one lol are ketogenic (leucine and lysine) and can be converted into ketone bodies which can be used as alternate fuel during periods of prolonged starvation.

Answer 62

Ketogenic AA (leucine and lysine) and can be converted into ketone bodies which can be used as alternate fuel during periods of prolonged starvation. The other ones are glucogenic AA (all except leucine and lysine) which can be converted to intermediates that feed into gluconeogenesis.

Answer 63

Glucose is converted into acetyl CoA through glycolysis and pyruvate dehydrogenase. It is not possible to convert acetyl CoA back into glucose. Most fatty acids are metabolize solely to acetyl CoA and therefore not a major source of glucose.

Answer 64

The important intermediates of gluconeogenesis are: Lactate Alanine Glycerol 3P This is important because there are enzymes that convert these intermediate into glycolytic intermediate. Lactate is converted to pyruvate by lactate dehydrogenase. Alanine is converted to pyruvate by alanine aminotransferase. Glycerol 3P is converted to dihydroxyacetone phosphate by glycerol 3P dehydrogenase.

Answer 65

Pyruvate carboxylase: mitochindral enzyme: produces oxaloacetate OAA, a citric acid cycle intermediate. Phosphoenolpyruvate carboxykinase (PEPCK): in cytoplasm: raise blood sugar levels by converting OAA to phosphoenolpyruvate (PEP). Fructose 1,6bphosphatase: in cytoplasm: RATE LIMITING point of gluconeogenesis, reverses PFK1 to make fructose 6P from fructose 1,6bP. Glucose 6 phosphatase: lumen of ER in liver cells: convert glucose 6P to free glucose to be transported back to cytoplasm (diffuses out of cell using GLUT transporters remember???)

Answer 66

Phosphatases oppose kinases. Kinases deliver p to molecules, phosphatases remove P from molecules. Think of them as “on/off” switches sort of kind of a little bit.

Answer 67

Pyruvate carboxylase is a mitochondrial enzyme that is activated by acetyl CoA and produces oxaloacetate (OAA). Interesting thing: OAA cannot leave the mitochondrion. It is reduced to malate through the malate-aspartate shuttle to the cytoplasm where it is oxidized to OAA. Acetyl CoA activates pyruvate carboxylase.

Answer 68

Pyruvate carboxylase produces oxaloacetate by carboxylation of pyruvate. Acetyl CoA inhibits pyruvate dehydrogenase because high levels of acetyl CoA implies that the cell is energetically satisfied and need not run the citric acid cycle forward (the cell should stop burning glucose) Pyruvate will be shunted through pyruvate carboxylase to help generate additional glucose through gluconeogenesis.

Answer 69

The source of acetyl CoA for glucogenesis is not from glycolysis and pyruvate dehydrogenase. The source of acetyl CoA for gluconeogenesis is fatty acids. Thus, to produce glucose in the liver during gluconeogenesis, fatty acids must be burned to provide this energy, stop the flow of the citric acid cycle, and produce massive amounts of OAA that can eventually lead to glucose production for the rest of the body.

Answer 70

PEPCK is an enzyme in the cytoplasm that is important for gluconeogenesis. PEPCK is induced by glucagon and cortisol, which act to raise blood sugar level levels. PEPCK converts OAA to phosphenolpyruvate (PEP), requires GTP. PEP then continues in the pathway to fructose 1,6bP. Pyruvate carboxylase and PEPCK circumvent the action of pyruvate kinase by converting pyruvate back into PEP. Remember that this process is all about producing glucose.

Answer 71

Fructose 1,6 bphosphatase in the cytoplasm is the rate limiting enzyme of gluconeogenesis. Frustose 1,6 bisphosphatase reverses PFK1, making fructose 6P from fructose 1,6bP. Fructose 1,6 bphosphatase is activated by ATP and inhibited by AMP and fructose 2,6 bP. Phosphatases do the opposite of kinases.

Answer 72

F2,6BP helps these cells override the inhibition of PFK1 that occurs when high levels of acetyl CoA are formed, signaling to the liver cell that it should shift its function from burning to storing fuel. Fructose-2,6-bisphosphate (F2,6BP) is a crucial metabolite that plays a key role in regulating glycolysis and gluconeogenesis by allosterically activating phosphofructokinase-1 (PFK-1) and inhibiting fructose-1,6-bisphosphatase.

Answer 73

Glucagon will lower F2,6BP and stimulate gluconeogenesis, whereas insulin will increase F2,6BP an inhibit glucogenesis. High levels of ATP imply that a cell is energetically satisfied enough to produce glucose for the rest of the body. High levels of AMP imply that a cell needs energy and cannot afford to produce energy for the rest of the body before satisfying its own requirements. F2,6BP is thought of as a marker for satisfactory energy levels in liver cells. It helps these cells override the inhibition of PFK1 that occurs when high levels of acetylCoA are formed, signaling to the liver cell that it should shift its function from burning to storing fuel. F2,6BP, produced by PFK2 controls, both gluconeogenesis and glycolysis (in the liver). PFK2 is activated by insulin and inhibited by glucagon. Thus, top of answer card. Read it again.

Answer 74

Enzyme in the lumen of the ER in liver cells that makes glucose from glucose 6P. Glucose 6 phosphatase is the last enzyme in gluconeogenesis. Glucose comes out of the cell using GLUT transporters. The absence of glucose six phosphatase in skeletal muscle means that muscle glycogen cannot serve as a source of blood glucose and rather is for use only within the muscle. Glucose six phosphatase circumvents glucokinase and hexokinase.

Answer 75

Glucose 6 phosphatase is found in the liver cells and is the final enzyme in gluconeogenesis. It dephosphorylates glucose 6P to glucose, which is then transported out of the cell into the bloodstream using GLUT for other tissues to use for metabolism. Muscle cells do not contain glucose 6 phosphatase as they do not send glucose into the bloodstream for other tissues to use for metabolism. They use the glucose 6P for their own metabolism. Alanine is the main glucogenic AA, but most of the others are glucogenic as well. Recalling that leucine and lysine are ketogenic AA. Glucose formed through gluconeogenesis does not serve as a metabolite for liver cells. Acetyl CoA from fatty acids cannot be converted back into glucose, but it can be converted to ketone bodies for alternative fuel for cells, including the brain. Think of ketones as a transportable form of acetyl CoA that is primarily utilized in periods of extended starvation.

Answer 76

Gluconeogenesis occur occurs when an individual has been fasting for more than 12 hours. To carry out gluconeogenesis, hepatic and renal cells must have enough energy to drive the process of glucose creation, which requires sufficient fats to undergo beta oxidation.

Answer 77

Acetyl CoA inhibits pyruvate dehydrogenase complex while activating pyruvate carboxylase. The net effect is to shift from burning pyruvate in the citric acid cycle to creating new glucose molecules for the rest of the body. The acetyl CoA for this regulation comes predominantly from beta oxidation, not glycolysis.

Answer 78

The last enzyme in gluconeogenesis is glucose 6 phosphatase. Patient with von Gierke’s disease are unable to perform gluconeogenesis in addition to glycogenolysis. This means that patients will be unable to produce glucose during periods of fasting (resulting from hypoglycemia). Furthermore, given a blocker in the glucogenic pathway, a buildup of intermediates (including lactate resulting in lactic acidosis) would also be expected.

Answer 79

The pentose phosphate pathway occurs in the cytoplasm of all cells which produces: NADPH ribose 5P for nucleotide synthesis and nucleic acid production (particularly DNA and RNA) Glucose 6 dehydrogenase is the rate limiting enzyme. Also known as the hexose monophosphate shunt (HMP shunt).

Answer 80

Rate limiting enzyme in pentose phosphate pathway. Start with glucose 6P and end with ribulose 5P. Irreversible. This enzyme produces NADPH and 6phosphogluconate. Induced by insulin and inhibited by NADPH (activated by NADP+).

Answer 81

Making a pool of sugars for biosynthesis, including ribulose 5P for nucleotide synthesis and nucleic acid production (DNA and RNA). Fructose 6P and glyceraldehyde 3P are among the sugars produced, which are intermediates of glycolysis and can go that way. Conversely, those intermediates can be made into pentoses for biosynthesis with transketolase and transaldolase.

Answer 82

NADPH and NADH are not the same thing. NAD+ is high energy electron acceptor (- potent oxidizing agent because it oxidizes other biomolecules while itself gets reduced). NADPH is an electron donor and this is a potent reducing agent as it helps other molecules be reduced while itself gets oxidized. Things it does include: Biosynthesis of fatty acids and cholesterol. Cellular bleach production in white blood cells, contributing to bactericidal activity. Maintenance of a supply of reduced glutathione to protect against reactive oxygen species (acting as an antioxidant).

Answer 83

NADPH and ribose 5P

Answer 84

Lipid biosynthesis Bactericidal bleach formation Maintenance of glutathione stores to protect against reactive oxygen species.

Answer 85

Enzymes that catalyze the incorporation of CO2 into organic substrates. For example. Pyruvate carboxylase adds a CO2 molecule to pyruvate to make oxaloacetate (OAA).