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BB2730 Metabolic Regulation > Glycogenesis > Flashcards

Glycogenesis Flashcards

1
Q

What happens to blood glucose levels after a meal?

A

Blood glucose levels rise as carbohydrates are digested and absorbed. Insulin is released to promote glucose uptake by cells, returning blood glucose to baseline.

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2
Q

What is the role of insulin in glucose regulation?

A

Insulin, secreted by pancreatic beta cells, promotes glucose uptake by cells, glycogen synthesis, and inhibits gluconeogenesis to lower blood glucose levels.

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3
Q

What is the role of glucagon in glucose regulation?

A

Glucagon, secreted by pancreatic alpha cells, stimulates glycogen breakdown and gluconeogenesis in the liver to increase blood glucose levels between meals.

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4
Q

How do snacks affect blood glucose levels?

A

Snacks cause smaller, transient increases in blood glucose, helping to prevent excessive dips, especially if meals are spaced far apart.

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5
Q

What is the normal blood glucose range?

A

Fasting: 70–100 mg/dL (3.9–5.6 mmol/L).
Postprandial (after a meal): Peaks below 140 mg/dL (7.8 mmol/L) in healthy individuals.

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6
Q

What happens in hyperglycemia?

A

Hyperglycemia occurs when blood glucose levels remain elevated due to insufficient insulin secretion or action, as seen in diabetes mellitus.

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7
Q

What happens in hypoglycemia?

A

Hypoglycemia occurs when blood glucose levels are too low due to excess insulin or insufficient glucose, causing symptoms like dizziness, confusion, and fatigue.

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8
Q

What is the role of incretins (GLP-1 and GIP) in glucose regulation?

A

Incretins are hormones that enhance insulin secretion after meals, aiding in the regulation of postprandial blood glucose levels.

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9
Q

How do foods with a high glycemic index affect blood glucose?

A

High glycemic index foods cause sharper and faster increases in blood glucose levels compared to low glycemic index foods, which result in slower glucose release.

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10
Q

How does epinephrine affect blood glucose levels?

A

Epinephrine increases blood glucose levels during stress by promoting glycogen breakdown and gluconeogenesis.

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11
Q

Why is blood glucose regulation important in diabetes management?

A

Proper regulation prevents hyperglycemia and hypoglycemia, reducing the risk of complications. Management includes monitoring glucose levels, insulin therapy, and dietary changes.

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12
Q

Which glucose transporter is used in the liver?

A

The liver uses GLUT-2, a high-capacity, low-affinity glucose transporter.

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13
Q

What is the role of GLUT-2 in the liver?

A

GLUT-2 facilitates the uptake of large amounts of glucose when blood glucose levels are high, such as after a meal.

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14
Q

What happens to glucose after it enters the liver?

A

Glucose is phosphorylated by glucokinase (Hexokinase IV) to form glucose-6-phosphate (G6P), which is used for glycogen synthesis, glycolysis, or the pentose phosphate pathway.

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15
Q

How does the liver contribute to glucose homeostasis?

A

The liver acts as a glucose buffer by taking up or releasing glucose to maintain stable blood glucose levels.

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16
Q

Which glucose transporter is used in muscle and adipose tissue?

A

Muscle and adipose tissues use GLUT-4, an insulin-dependent glucose transporter.

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17
Q

How is GLUT-4 regulated in muscle and adipose tissue?

A

GLUT-4 is stored in vesicles and translocates to the plasma membrane in response to insulin binding to its receptor.

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18
Q

What happens to glucose after it enters muscle and adipose tissue?

A

In muscle: Glucose is stored as glycogen or used for energy.
In adipose tissue: Glucose is converted into lipids for storage.

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19
Q

What is insulin resistance?

A

Insulin resistance is a condition where insulin signaling is impaired, reducing GLUT-4 translocation and glucose uptake in muscle and adipose tissues.

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20
Q

What are the consequences of insulin resistance?

A

Insulin resistance leads to hyperglycemia (elevated blood glucose levels) and is a hallmark of type 2 diabetes.

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21
Q

How does exercise affect GLUT-4 activity?

A

Exercise promotes GLUT-4 translocation in muscle independent of insulin, enhancing glucose uptake and improving blood glucose control.

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22
Q

How does glucose uptake differ between the liver and muscle/adipose tissue?

A

Liver: Uses insulin-independent GLUT-2 for glucose uptake.
Muscle/Adipose Tissue: Use insulin-dependent GLUT-4 for glucose uptake.

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23
Q

What are therapeutic strategies for improving glucose uptake in diabetes?

A

Metformin: Targets the liver to reduce glucose production.
Insulin therapy: Improves GLUT-4 translocation.
Insulin sensitizers: Enhance insulin signaling in muscle and adipose tissues.

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24
Q

Why is GLUT-2’s low affinity for glucose important?

A

GLUT-2’s low affinity ensures it takes up glucose efficiently only when blood glucose levels are high, such as after a meal.

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25
Q

What is the function of GLUT transporters?

A

GLUT transporters mediate facilitated diffusion, allowing glucose to cross cell membranes down its concentration gradient without requiring energy (ATP).

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26
Q

What is the function of SGLT transporters?

A

SGLT transporters mediate active glucose transport, coupling glucose uptake with sodium ion movement (co-transport) against its concentration gradient, requiring energy.

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27
Q

Where is GLUT-1 found, and what is its role?

A

Location: Erythrocytes, blood-tissue barriers (e.g., blood-brain barrier).
Function: Ensures basal glucose uptake in tissues with constant energy demands.

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28
Q

Where is GLUT-2 found, and what is its role?

A

Location: Liver, intestine, kidney, brain, pancreatic beta cells.
Function: Facilitates bidirectional glucose transport and glucose sensing in pancreatic beta cells.

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29
Q

What is the primary role of GLUT-3?

A

GLUT-3 has a high affinity for glucose and ensures efficient glucose uptake in cells with high energy demands, such as neurons.

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30
Q

Where is GLUT-4 found, and why is it important?

A

Location: Skeletal muscle, cardiac muscle, adipose tissue.
Function: Insulin-dependent transporter for glucose uptake after meals, translocating to the plasma membrane in response to insulin.

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31
Q

What is GLUT-5 specialized for?

A

GLUT-5 is specialized for fructose transport and is primarily expressed in the intestine.

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32
Q

Where is SGLT-1 found, and what is its role?

A

Location: Intestine and kidneys.
Function: Responsible for glucose and galactose absorption in the small intestine and glucose reabsorption in the renal proximal tubules.

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33
Q

Where is SGLT-2 found, and what is its role?

A

Location: Kidney.
Function: Reabsorbs 90% of glucose in the renal proximal tubules, preventing glucose loss in urine.

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34
Q

What happens when GLUT-4 function is impaired?

A

Impaired GLUT-4 translocation in insulin resistance leads to reduced glucose uptake in muscle and adipose tissue, contributing to hyperglycemia in type 2 diabetes.

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35
Q

How do SGLT-2 inhibitors help in diabetes management?

A

SGLT-2 inhibitors block glucose reabsorption in the kidney, promoting glucose excretion in urine and lowering blood sugar levels.

36
Q

What is the significance of GLUT-1 upregulation in cancer?

A

GLUT-1 is often upregulated in tumors with high glucose demand, facilitating glucose uptake for energy and rapid cell growth.

37
Q

What role does GLUT-2 play in glucose homeostasis?

A

GLUT-2 in pancreatic beta cells senses blood glucose levels, enabling appropriate insulin secretion to regulate glucose homeostasis.

38
Q

What clinical condition is linked to GLUT-5 dysfunction?

A

GLUT-5 dysfunction can lead to fructose malabsorption, causing gastrointestinal symptoms.

39
Q

How is glucose uptake regulated in the kidneys?

A

SGLT-1: Absorbs glucose in the intestine and kidney with a 2Na⁺/1 glucose ratio.
SGLT-2: Reabsorbs 90% of glucose in the kidney using a 1Na⁺/1 glucose ratio.

40
Q

What is glycogen synthesis, and when does it occur?

A

Glycogen synthesis (glycogenesis) stores excess glucose as glycogen in the liver and muscle. It occurs when blood glucose levels are high, such as after a meal.

41
Q

What enzyme is responsible for glycogen synthesis?

A

Glycogen synthase is the enzyme responsible for glycogen synthesis.

42
Q

What is glycogen breakdown, and when does it occur?

A

Glycogen breakdown (glycogenolysis) converts glycogen into glucose-6-phosphate to provide glucose during fasting or low blood glucose states.

43
Q

What enzyme is responsible for glycogen breakdown?

A

Glycogen phosphorylase is the enzyme responsible for glycogen breakdown.

44
Q

What is the role of glucose-6-phosphate in glucose homeostasis?

A

Glucose-6-phosphate serves as a central intermediate for glycolysis, gluconeogenesis, the pentose phosphate pathway, and glycogen metabolism.

45
Q

What is the pentose phosphate pathway?

A

The pentose phosphate pathway converts glucose-6-phosphate into ribose-5-phosphate (for nucleotide synthesis) and NADPH (for anabolic reactions).

46
Q

What happens to pyruvate under aerobic conditions?

A

Pyruvate is converted to acetyl-CoA in the mitochondria, which enters the citric acid cycle for ATP production or serves as a precursor for fatty acid synthesis.

47
Q

What happens to pyruvate under anaerobic conditions?

A

Pyruvate is converted to lactate in the cytoplasm through the action of lactate dehydrogenase.

48
Q

What is gluconeogenesis, and when does it occur?

A

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (e.g., lactate, amino acids). It occurs during fasting or low glucose availability.

49
Q

What are the precursors for gluconeogenesis?

A

The main precursors are lactate, amino acids, and glycerol.

50
Q

What is the role of acetyl-CoA in glucose metabolism?

A

Acetyl-CoA is a key intermediate that enters the citric acid cycle for ATP production and serves as a precursor for lipid synthesis.

51
Q

How is glucose homeostasis maintained in the fed state?

A

Glucose is utilized for energy (glycolysis).
Excess glucose is stored as glycogen (glycogenesis) or converted to lipids (lipogenesis).

52
Q

How is glucose homeostasis maintained in the fasting state?

A

Glycogenolysis and gluconeogenesis provide glucose to maintain blood glucose levels.
Fatty acids and ketones serve as alternative energy sources.

53
Q

What happens during exercise or stress to glucose metabolism?

A

Glycogen stores are rapidly mobilized for energy through glycogenolysis, and lactate is recycled via the Cori cycle.

54
Q

How does diabetes mellitus affect glucose homeostasis?

A

In diabetes, dysregulation of glycogen metabolism or gluconeogenesis leads to hyperglycemia due to impaired insulin function.

55
Q

What is the role of insulin in glucose homeostasis?

A

Insulin promotes glycogenesis and glycolysis while inhibiting gluconeogenesis to reduce blood glucose levels.

56
Q

What is the role of glucagon in glucose homeostasis?

A

Glucagon promotes glycogenolysis and gluconeogenesis to increase blood glucose levels during fasting.

57
Q

What is the citric acid cycle’s role in glucose metabolism?

A

The citric acid cycle uses acetyl-CoA to produce ATP, linking carbohydrate, fat, and protein metabolism.

58
Q

How can enzyme deficiencies affect glucose homeostasis?

A

Deficiencies in enzymes like phosphofructokinase (glycolysis) or glucose-6-phosphatase (gluconeogenesis) disrupt glucose metabolism and homeostasis.

59
Q

What is glycogenesis?

A

Glycogenesis is the process of synthesizing glycogen from surplus glucose, primarily in the liver and muscle, for energy storage.

60
Q

What bonds link glucose molecules in glycogen?

A

α-1,4-glycosidic bonds: Link glucose molecules in linear chains.
α-1,6-glycosidic bonds: Form branch points in glycogen.

61
Q

What is the role of glycogenin in glycogenesis?

A

Glycogenin is the core protein that acts as a primer, initiating glycogen synthesis by attaching the first few glucose molecules.

62
Q

What are the steps of glycogenesis?

A

Activation of glucose:
Glucose → Glucose-6-phosphate → Glucose-1-phosphate → UDP-glucose.
Elongation:
Glycogen synthase adds glucose via α-1,4-glycosidic bonds.
Branching:
Branching enzyme forms α-1,6-glycosidic bonds, creating branch points.

63
Q

What enzyme adds glucose to glycogen chains during elongation?

A

Glycogen synthase adds UDP-glucose to glycogen, forming α-1,4-glycosidic bonds.

64
Q

What enzyme creates branches in glycogen?

A

Branching enzyme introduces α-1,6-glycosidic bonds, forming new branch points.

65
Q

What is the difference between liver glycogen and muscle glycogen?

A

Liver glycogen: Maintains blood glucose levels during fasting.
Muscle glycogen: Provides energy for muscle contraction during exercise.

66
Q

How is glycogenesis regulated by insulin?

A

Insulin stimulates glycogenesis by activating glycogen synthase and inhibiting glycogen breakdown (glycogen phosphorylase).

67
Q

What happens to glycogen during exercise?

A

Muscle glycogen is broken down into glucose to provide energy for muscle contraction during exercise.

68
Q

What are glycogen storage diseases?

A

Glycogen storage diseases are genetic disorders caused by enzyme deficiencies in glycogenesis or glycogenolysis, such as von Gierke’s or Pompe’s disease.

69
Q

What is the importance of branching in glycogen structure?

A

Branching increases glycogen solubility and provides multiple sites for glucose addition or release, making glycogen a more efficient energy storage molecule.

70
Q

What role does glycogenesis play after eating?

A

Glycogenesis stores excess glucose as glycogen in the liver and muscles to prevent hyperglycemia and provide energy reserves.

71
Q

What happens to glycogen in diabetes mellitus?

A

In diabetes, impaired insulin function reduces glycogenesis, leading to hyperglycemia and inefficient glucose storage.

72
Q

How is glycogen used during fasting?

A

Liver glycogen is broken down into glucose (glycogenolysis) to maintain blood glucose levels during fasting.

73
Q

Why is glycogen important for recovery after exercise?

A

Post-exercise, glycogen stores need to be replenished to restore energy reserves and prepare for future physical activity.

74
Q

What are the two forms of glycogen synthase?

A

Active form (a): Dephosphorylated, promotes glycogen synthesis.
Inactive form (b): Phosphorylated, less active or inactive.

75
Q

How does insulin regulate glycogen synthase?

A

Insulin activates protein phosphatase 1 (PP1), which dephosphorylates and activates glycogen synthase. Insulin also inhibits GSK3, preventing glycogen synthase phosphorylation.

76
Q

How do glucagon and epinephrine regulate glycogen synthase?

A

Glucagon and epinephrine activate kinases (e.g., GSK3) that phosphorylate glycogen synthase, converting it to the inactive (b) form and inhibiting glycogen synthesis.

77
Q

What is the role of protein phosphatase 1 (PP1) in glycogen synthase regulation?

A

PP1 dephosphorylates glycogen synthase, converting it to the active form (a). It is activated by insulin and glucose-6-phosphate.

78
Q

What is the role of glycogen synthase kinase 3 (GSK3)?

A

GSK3 phosphorylates glycogen synthase, converting it to the inactive form (b). Insulin inhibits GSK3 to promote glycogen synthesis.

79
Q

What does casein kinase II (CKII) do in glycogen synthase regulation?

A

CKII adds a priming phosphate group to glycogen synthase, allowing GSK3 to further phosphorylate and inactivate it.

80
Q

How does glucose-6-phosphate regulate glycogen synthase?

A

Glucose-6-phosphate allosterically activates glycogen synthase by enhancing its affinity for dephosphorylation and signaling high glucose availability.

81
Q

What happens to glycogen synthase during the postprandial state?

A

High blood glucose stimulates insulin release, activating PP1 and dephosphorylating glycogen synthase to store glucose as glycogen.

82
Q

What happens to glycogen synthase during fasting or stress?

A

Glucagon and epinephrine promote glycogen synthase phosphorylation, inhibiting glycogen synthesis and prioritizing glycogen breakdown (glycogenolysis).

83
Q

What is the effect of insulin resistance on glycogen synthase?

A

In insulin resistance, reduced PP1 activity and sustained GSK3 activity lead to decreased glycogen synthase activation, impairing glycogen synthesis and contributing to hyperglycemia.

84
Q

What role does glycogen synthase play in glycogen storage diseases?

A

Mutations in glycogen synthase can result in glycogen storage diseases, causing defective glycogen synthesis and impaired glucose storage.

85
Q

What is the role of GSK3 inhibitors in diabetes treatment?

A

GSK3 inhibitors enhance glycogen synthesis by preventing glycogen synthase phosphorylation, making them potential treatments for diabetes.

86
Q

Why is PP1 crucial for glycogen synthase activation?

A

PP1 removes phosphate groups from glycogen synthase, converting it to its active form and promoting glycogen synthesis.

BB2730 Metabolic Regulation (4 decks)

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