Ch 9 - Carbohydrate Metabolism I Flashcards

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1
Q

Where is GLUT2 found? Can it be saturated at normal glucose levels and is it responsive to insulin?

A
  • in the liver for glucose storage
  • in pancreatic beta-islet cells as part of the glucose sensor
  • have a high Km
  • cannot be saturated under normal physiological conditions
  • not responsive to insulin
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2
Q

Where is GLUT4 found? Can it be saturated at normal glucose levels and is it responsive to insulin?

A
  • in adipose tissue and muscle and is stimulated by insulin
  • has a low Km
  • saturated when glucose levels are only slightly above 5mM
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3
Q

Where does glycolysis occur and what does it produce?

A
  • occurs in the cytoplasm of all cells and does not require oxygen
  • yields 2 ATP per molecule of glucose
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4
Q

What is glucokinase role in glycolysis?

A
  • phosphorylates and traps glucose in liver and pancreatic cells to form glucose 6-phosphate
  • works with GLUT2, present in the pancreatic beta-islet cells as part of the glucose sensor and is responsive to insulin in the liver
  • high Km (acts on glucose proportionally to its concentration)
  • induced by insulin in hepatocytes
  • irreversible
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5
Q

What is hexokinase role in glycolysis?

A
  • phosphorylates glucose to form glucose 6-phosphate in peripheral tissues, trapping glucose in the cell
  • low Km (reaches maximum velocity at low [glucose])
  • inhibited by glucose-6-phosphate
  • irreversible
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6
Q

What is phosphofructokinase-1 (PFK-1) role in glycolysis?

A
  • rate limiting step of glycolysis (main control point)
  • phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate using ATP
  • activated by AMP and fructose 2,6-bisphosphate (F2,6-BP) and is inhibited by ATP, citrate, and glucagon
  • irreversible
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7
Q

What is phosphofructokinase-2 (PFK-2) role in glycolysis?

A

produces the F2,6-BP that activates PFK-1

- activated by insulin and inhibited by glucagon

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8
Q

What is glyceraldehyde-3-phosphate dehydrogenase role in glycolysis?

A

produces NADH, which can feed into the electron transport chain, while phosphorylating 3-phosphate to 1,3-bisphosphate
- reversible

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9
Q

What is 3-phosphoglycerate kinase and pyruvate kinase roles in glycolysis?

A
  • each perform substrate level phosphorylation, placing an inorganic phosphate onto ADP to form ATP
  • 3: transfer phosphate from 1,3-diphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate (reversible)
  • pyruvate: transfer phosphate from PEP to ADP, forming ATP and pyruvate (irreversible)
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10
Q

Which enzymes catalyze irreversible reactions in glycolysis?

A
How Glycolysis Pushes Forward the Process: Kinases
Hexokinase
Glucokinase
PFK-1
Pyruvate Kinase
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11
Q

What oxidizes the NADH produced in glycolysis?

A
  • the mitochondrial electron transport chain when oxygen is present
  • if oxygen or mitochondria is absent, oxidized by the cytoplasmic lactate dehydrogenase (ex. RBCs, skeletal muscle, any cell deprived of oxygen)
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12
Q

Where does galactose come from and what does it do?

A
  • comes from lactose in milk
  • trapped in cell by galactokinase, and converted to glucose 1-phosphate via galactose-1-phosphate uridyltransferase and an epimerase
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13
Q

Where does fructose come from and what does it do?

A
  • comes from honey, fruit, and sucrose

- trapped in the cell by fructokinase, and then cleaved by aldolase B to form glyceraldehyde and DHAP

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14
Q

What is pyruvate dehydrogenase?

A
  • a complex of enzymes that convert pyruvate to acetyl-CoA

- stimulated by insulin and inhibited by acetyl-CoA

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15
Q

What is glycogenesis?

A

the production of glycogen using 2 main enzymes: glycogen synthase and branching enzyme

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16
Q

What does glycogen synthase do in glycogenesis?

A
  • rate limiting step for glycogenesis
  • creates alpha-1,4 glycosidic links between glucose molecules
  • activated by insulin in liver and muscle
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17
Q

What do branching enzymes do in glycogenesis?

A

moves a block of oligoglucose from one chain and adds it to the growing glycogen as a new branch using an alpha-1,6 glycosidic link

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18
Q

What is glycogenolysis?

A

the breakdown of glycogen using 2 main enzymes: glycogen phosphorylase and debranching enzymes

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19
Q

What does glycogen phosphorylase do in glycogenolysis? How is it activated in liver v skeletal muscle?

A
  • rate limiting step for glycogenolysis
  • removes single glucose 1-phosphate molecules by breaking alpha-1,4, glycosidic links
  • in liver, it is activated by glucagon to prevent low blood sugar
  • in exercising skeletal muscle, it is activated by epinephrine and AMP to provide glucose for the muscle itself
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20
Q

What do debranching enzymes do in glycogenolysis?

A
  • moves a block of oligoglucose from one branch and connects it to the chain using an alpha-1,4, glycosidic link
  • also removes the branchpoint, which is connected via an alpha-1,6, glycosidic link, releasing a free glucose molecule
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21
Q

What is gluconeogenesis and where does it occur?

A
  • occurs in both cytoplasm and mitochondria, predominantly in the liver (small kidney contribution)
  • most is simply the reverse of glycolysis, using the same enzymes
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22
Q

How does pyruvate carboxylase help in bypassing the irreversible steps of glycolysis in gluconeogenesis?

A
  • pyruvate carboxylase converts pyruvate into oxaloacetate, which is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK)
  • together, these enzymes bypass pyruvate kinase
  • pyruvate carboxylase is activated by acetyl-CoA from beta oxidation; PEPCK is activated by glucagon and cortisol
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23
Q

How does fructose-1,6-bisphosphate help in bypassing the irreversible steps of glycolysis in gluconeogenesis?

A
  • rate limiting step for gluconeogenesis
  • converts fructose 1,6-bisphosphate to fructose-6-phosphate, bypassing phosphofructokinase-1
  • this is the rate limiting step of gluconeogenesis
  • activated by ATP directly and glucagon indirectly (via decreased levels of fructose-2,6-bisphosphate)
  • inhibited by AMP directly and insulin indirectly (via increased levels of fructose-2,6-bisphosphate)
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24
Q

How does glucose-6-phosphatase help in bypassing the irreversible steps of glycolysis in gluconeogenesis?

A
  • converts glucose-6-phosphate to free glucose, bypassing glucokinase
  • found only in the endoplasmic reticulum of the liver
25
Q

When does the pentose phosphate pathway (PPP) occur?

A
  • hexose monophosphate (HMP) shunt
  • occurs in the cytoplasm of most cells, generating NADPH and sugars for biosynthesis (derived from ribulose 5-phosphate)
26
Q

What is the rate limiting enzyme in the pentose phosphate pathway?

A

glucose-6-phosphate dehydrogenase, which is activated by NADP+ and insulin and inhibited by NADPH

27
Q

What is Km?

A
  • the concentration of substrate when an enzyme is active at half of its maximum velocity
  • the lower the Km, the higher the enzyme’s affinity for the substrate
28
Q

How does insulin promote glucose entry into cells?

A
  • GLUT4 is saturated when glucose levels are only slightly above 5mM, so glucose entry can only be increased by increasing the number of transporters
  • insulin promotes the fusion of vesicles containing preformed GLUT4 with the cell membrane
29
Q

How does RBCs extruding their mitochondria during development help them carry out their function of carrying oxygen?

A
  • maximizing volume available for hgb, the primary oxygen-carrying protein
  • stopping RBCs from utilizing the oxygen it’s supposed to be carrying to oxygen-depleted bodily tissues
30
Q

What is fermentation and what is its rate limiting step?

A
  • occurs in the absence of oxygen
  • lactate dehydrogenase (rate limiting) oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
31
Q

How do we adapt to high altitudes?

A
  • increased respiration
  • increased oxygen affinity for hgb (initial)
  • increased rate of glycolysis
  • increased [2,3-BPG] in RBC (over 12-24 hr period)
  • normalized oxygen affinity y the increased level of 2,3-BPG
  • increased hgb (over days to weeks)
32
Q

Why must pyruvate undergo fermentation for glycolysis to continue?

A
  • fermentation must occur to regenerate NAD+, which is in limited supply in cells
  • fermentation generates no ATP or energy carriers; it merely regenerates the coenzymes needed in glycolysis
33
Q

Why is it necessary that fetal hgb does not bind 2,3-BPG?

A
  • the binding of 2,3-BPH decreases hgb’s affinity for oxygen
  • fetal hgb must be able to “steal” oxygen from maternal hgb at the placental interface; therefore, it would be disadvantageous to lower its affinity for oxygen
34
Q

Why does a high fructose drink supply a quick source of energy in both aerobic and anaerobic cells?

A

because dihydroxyacetone phosphate (DHAP) and glyceraldehyde, the products of fructose metabolism are downstream from the key regulatory and rate limiting enzyme of glycolysis (PFK-1)

35
Q

Which enzyme is responsible for trapping galactose in the cell? What enzyme in galactose metabolism results in a product that can feed directly into glycolysis, linking the 2 pathways?

A
  • galactose is phosphorylated by galactokinase, trapping it in the cell
  • galactose-1-phosphate uridyltransferase produces glucose-1-phosphate, a glycolytic intermediate, this linking the pathways
36
Q

Which enzyme is responsible for trapping fructose in the cell? What enzyme in fructose metabolism results in a product that can feed directly into glycolysis, linking the 2 pathways?

A
  • fructose is phosphorylated by fructokinase, trapping it in the cell (with a small contribution from hexokinase)
  • aldolase B produces dihydroxyacetone phosphate (DHAP) and glyceraldehyde (which can be phosphorylated to form glyceraldehyde 3-phosphate), which are glycolytic intermediates, this linking the pathways
37
Q

What are the reactants of the pyruvate dehydrogenase complex? What are the produts?

A
  • pyruvate, NAD+, and CoA are the reactants

- Acetyl-CoA, NADH, and CO2 are the products

38
Q

How does acetyl-CoA affect PDH complex activity and why?

A
  • 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 the be used to form other products, such as oxaloacetate for use in gluconeogenesis
39
Q

What is the difference between glycosyl alpha-1,4 and alpha-1,6 transferase in branching enzymes?

A
  • 1,4 keeps the same branch moving 4ward

- 1,6 puts a branch in the mix

40
Q

What is the structure of glycogen? What types of glycosidic links exist in a glycogen granule?

A
  • made of a core protein of glycogenin with linear chains of glucose emanating out from the center, connected by alpha-1,4, glycosidic links
  • some of these chains are branched, which requires alpha-1,6 glycosidic links
41
Q

What are the 2 main enzymes of glycogenesis and what does each do?

A
  • glycogen synthase attaches the glucose molecules from UDP-glucose to the growing glycogen chain, forming an alpha-1,4 link in the process
  • 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
42
Q

What are the 2 main enzymes of glycogenolysis and what does each do?

A
  • glycogen phosphorylase removes a glucose molecule from glycogen using a phosphate, breaking the alpha-1,4 link and creating glucose-1-phosphate
  • 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 branchpoint is left behind; this is removed by breaking the alpha-1,6 link to form a free molecule of glucose
43
Q

What are the counterregulatory hormones to insulin?

A

glucagon, epinephrine, cortisol, and growth hormones which act to raise blood glucose levels by stimulating glycogenolysis and gluconeogenesis

44
Q

What does gluconeogenesis need different enzymes to allow the body to revert pyruvate to glucose?

A

because glycolysis has 3 irreversible steps (hexokinase, PFK-1, and pyruvate kinase)

45
Q

Why does gluconeogenesis require acetyl-CoA to occur and what does this cause?

A
  • to inhibit pyruvate dehydrogenase and stimulate pyruvate carboxylase
  • gluconeogenesis is inextricably linked to fatty acid oxidation
  • the source of acetyl-CoA cannot be glycolysis because this would just burn the glucose that is being generating in gluconeogenesis
46
Q

Under what physiological conditions should the body carry out gluconeogenesis?

A
  • gluconeogenesis occurs when an individual has been fasting for > 12 hours
  • to carry out gluconeogenesis, hepatic (renal) cells must have enough energy to drive the process of glucose creation, which requires sufficient fat stores to undergo beta oxidation
47
Q

What are the 4 enzymes unique to gluconeogenesis and which irreversible glycolytic enzymes do they replace?

A
  • pyruvate carboxylase replaces pyruvate kinase
  • PEPCK replaces pyruvate kinase
  • fructose-1,6-bisphosphate replaces PFK-1
  • glucose-6-phosphatase replaces glucokinase
48
Q

How does acetyl-CoA shift the metabolism of pyruvate?

A
  • 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
49
Q

What is the difference between NAD+ and NADH?

A
  • NADH+ is an energy carrier

- NADH is used in biosynthesis, in the immune system, and to help prevent oxidative damage

50
Q

What are the 2 major metabolic products of the pentose phosphate pathway (PPP)?

A
  • ribose 5-phosphate

- NADPH

51
Q

What are the 3 primary functions of NADPH?

A
  • involved in lipid biosynthesis
  • bactericidal bleach formation in certain WBCs
  • maintenance of glutathione stores to protect against reactive oxygen species
52
Q

What is the difference between pyruvate under normal conditions v during strenuous exercise?

A
  • when oxygen is readily available, pyruvate generated in glycolysis is converted into acetyl-CoA by pyruvate dehydrogenase
  • during exercise, especially in poor physical conditions, the oxygen demands of the skeletal muscle may exceed the ability of the heart and lungs to provide oxygen so the muscle switch to anaerobic glycolysis and the pyruvate that is produced is fermented to lactate by lactate dehydrogenase
53
Q

Which organ does not require a constant supply of glucose from the blood for energy during a fast?

A
  • the liver, like all cells, needs a constant supply of glucose; however, it is able to produce its own glucose through gluconeogenesis (cells in kidneys can also complete low levels of gluconeogenesis)
54
Q

After an overnight fast, which enzyme would be expected to have little, if any, physiological activity?

A
  • after an overnight fast, the liver is producing glucose and glucokinase activity would be insignificant
  • glucokinase is used to trap extra glucose in liver cells as part of a storage mechanism; with low blood glucose, liver cells would be generating new glucose, not storing it (also in the pancreas where it serves as a glucose sensor; if glucose levels are low, it has little activity in this tissue as well)
  • other enzymes used in glycolysis the citric acid cycle, or gluconeogenesis would be expected to maintain normal activity after an overnight fast, using glucose derived from glycogen or gluconeogenesis, rather than orally ingested glucose
55
Q

What is expected of mitochondrial pyruvate when fatty acid beta oxidation predominates in the liver?

A
  • pyruvate is converted primarily into 3 main intermediates: acetyl-CoA (citric cycle), lactate (fermentation), and oxaloacetate (gluconeogenesis)
  • high levels of acetyl-CoA, which is produced during beta-oxidation, will inhibit pyruvate dehydrogenase and shift the citric acid cycle to run in the reverse direction, producing oxaloacetate for gluconeogenesis
56
Q

After an overnight fast, what process would be expected to occur at an elevate rate compared with the well-fed state?

A
  • after a fast, the liver most contribute glucose into the bloodstream through 2 main processes: glycogenolysis (early to intermediate fasting) and gluconeogenesis (intermediate to late fasting)
57
Q

Which glycolysis enzyme would be affected by citrate?

A
  • citrate is produced by citrate synthase from acetyl-CoA and oxaloacetate which occurs in the mitochondria
  • when the citric acid cycle slows down, citrate accumulates
  • in the cytosol, it acts as a negative allosteric regulator of PFK-1, rate limiting step of glycolysis
58
Q

What would be expected after a brief period of intense exercise that greatly increases the activity of muscle pyruvate dehydrogenase?

A
  • PDH to be highly active to generate ATP
  • ADP levels should be high because ATP was just burned by the muscle
  • acetyl-CoA, is an inhibitor of PDH, causing a shift of pyruvate into the gluconeogenic pathway
59
Q

After a large, well-balanced meal, which substance would be expected to be elevated: fatty acids, insulin, glucose, or glucagon?

A
  • one would expect blood to contain high levels of nutrients such as glucose and fatty acids as well as regulators telling the body to utilize and store this fuel, like insulin
  • glucagon is a peptide hormone used to raise blood sugar levels by promoting, among other processes, glycogenolysis and gluconeogenesis (would be elevated while fasting)