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Biochem 102 > Integration of Metabolism > Flashcards

Integration of Metabolism Flashcards

1
Q

What 4 major tissues play a role in energy metabolism

A
  • Liver, adipose, muscle, brain
  • each specialized in storage, use of specialized fuels
  • form a network in which one tissue provides substrates to another
  • communication mediated by nervous system
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2
Q

Integration of energy metabolism is controlled by which two peptide hormones?

A
  • Insulin and glucagon
  • Secreted in response to changing substrate levels in blood
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2
Q

Catecholamines play a supporting role

A
  • Epinephrine and norepinephrine- secreted in response to neutral signals from brain
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2
Q

Changes in conc. of two hormones allow what?

A

Body to store energy after eating, or make stored energy available during fasting, injury or fight or flight

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3
Q

Insulin vs. Glucagon

A

Insulin: inc. glucose ox., glycogen synthesis, fat synthesis, protein synthesis
Glucagon: inc. glycogenolysis, gluconeogenesis, ketogenesis

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4
Q

Insulin

A

Most important hormone controlling energy use by tissues

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5
Q

What are the metabolic effects of insulin?

A

Anabolic
- well fed state
- promotes storage of energy
- promotes synthesis of glycogen, fat and protein

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6
Q

Where is insulin synthesized

A

peptide hormone synthesized is the b-cells of islets of langerhans in the pancreas

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7
Q

Structure of Insulin

A
  • Insulin is composed of 51 amino acids in two protein chains (A and B chain)
  • The two chains are joined by 2 intermolecular disulfide bonds
  • The A chain also contains an intramolecular disulfide bond
  • mostly a-helical
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8
Q

Synthesis of Insulin

A
  • Involves 2 inactive precursors: preproinsulin and proinsulin
  • Precursors are sequentially cleaved to form mature insulin and c-peptide
  • C-peptide is essential for protein folding
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9
Q

Where is Insulin stored

A
  • Stored in cytosolic granules and released by exocytosis when glucose levels are high
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10
Q

Plasma half life of insulin

A
  • 6 mins (short)
  • Rapid turnover once released = rapid changes in circulated changes
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11
Q

Stimulation of Insulin Secretion

A
  1. Glucose
  2. Amino Acids
  3. Gastrointestinal hormone
    (mirror images for spike of glucose corresponding to spike in insulin)
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12
Q
  1. Glucose
A

Inc. plasma glucose conc. is the most important signal for increased insulin secretion

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13
Q
  1. Amino Acids
A

Eating protein causes rise in plasma a.a, inducing insulin secretion (fatty acids have similar effect)

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14
Q
  1. Gastrointestinal Hormones
A

Ingestion of food causes the release of intestinal hormones that stimulate insulin secretion

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15
Q

Inhibition of Insulin Secretion

A
  1. Decreased food ingestion (lower blood glucose)
  2. Periods of physiological stress - injury or infection
    - mediated by norepinephrine and epinephrine
    - catecholamines cause rapid mobilization of energy-yielding fuels
    - can override glucose-stimulated insulin release in emergency situations
16
Q

Metabolic Effects of Insulin

A
  • Insulin promotes nutrient storage in glycogen, TAG and protein and inhibits their mobilization
    1. Effects on Carbohydrate metabolism
    2. Effects on lipid metabolism
    3. Effects on protein synthesis
17
Q
  1. Effects on Carbohydrate metabolism
A

Most pronounced in liver, muscle, adipose
- In liver and muscle glycogen synthesis is increased
- in muscle and adipose glucose uptake is increased by inc. the number of glucose transporters in the membrane
- In liver glucose production is decreased through inhibition of glycogen degradation and gluconeogenesis

18
Q
  1. Effects on lipid metabolism
A
  • In adipose tissue release of FA is decreased by two mechanisms (inhibiting hormone sensitive lipase activity resulting in decreased TAG breakdown and increasing TAG synthesis by inc. glucose transport and metabolism in fat cells resulting resulting in inc. glycerol 3-P levels)
  • Activity of lipoprotein lipase is inc. resulting in more FFA from lipoproteins (VLDL/chylomicrons) available for TAG formation
19
Q
  1. Effects on protein synthesis
A
  • Insulin stimulates entry of a.a into the cells
  • Stimulates protein synthesis
20
Q

Signal Transduction Pathway

A

Ways signals from outside the cell can change the overall activity of the cell
- External signal received by receptor, amplifies signal, transduction in pathways, results in respone

21
Q

Insulin Receptor

A
  • Insulin binds to specific receptor in cell membrane (can’t cross membrane on own)
  • Insulin receptor is found on most tissues, including liver, adipose and muscle
  • binding to receptor is firsts step that leads to cascade of rxns ultimately leading to diverse array of biological responses to insulin signal
22
Q

Mechanism of Action

A
  • Binding of insulin to the a-subunit activates the receptor, changing its shape
  • Initiates signal transduction by autophosphorylation of Tyr on receptor - locks in active site
23
Q

Insulin mechanism of action

A
  • Signal transduction is a series of phosphorylation rxns of insulin receptor substrate proteins
  • Signal stops when receptor is dephosphorylated
24
Q

Insulin-Dependent Glucose Transport

A
  • Muscle and adipose tissues experience inc. glucose uptake in response to insulin
  • Mediated through inc. glucose transporters in the cell membrane in response to insulin
  • Binding of insulin to insulin receptor causes intracellular glucose transporters to move to the cell membrane
  • Inc. insulin dependent transport of glucose into cell
  • Dec. insulin leads to internalization of glucose transporters untl more insulin is detected
25
Q

Glucagon

A
  • Peptide hormone secreted by a-cells of the pancreatic islets of Langerhans
  • Glucagon (epinephrine/norepniphrine) oopose actions of insulin
26
Q

Most important role of glucagon

A

Maintain blood glucose levels by activating glycogen degradation and gluconeogenesis in the liver

27
Q

Structure of Glucagon

A

Glucagon is a signle peptide of 29 a.a
- similar to insulin it starts as preproglucagon and is converted to glucagon by a series of proteolytic cleavages

28
Q

Stimulation of Glucagon Secretion

A
  1. Low blood glucose
  2. Amino Acids
  3. Catecholamines
29
Q
  1. Low blood glucose
A

Dec. in plasma glucose conc. is primary stimulus for glucagon release, during overnight or prolonged fast, glucagon prevents hypoglycemia

30
Q
  1. Amino Acids
A

Derived form protein rich meal. Glucagon prevents hypoglycemia that would other wise occur as a result of inc. insulin secretion

31
Q
  1. Catecholamines
A

Elevated levels of epinephrine/norepinephrine increase glucagon secretion
- During periods of physiological stress, regardless of blood glucose level, glucagon is elevated in anticipation of inc. glucose use

32
Q

Inhibition of Glucagon Secretion

A

Elevated blood glucose
- Insulin (both elevated after glucose or carbohydrate-rich meal)

33
Q

Metabolic Effects of Glucagon

A
  1. Carbohydrate metabolism
  2. Lipid metabolism
  3. Protein metabolism
    - effects are catabolic and promote the maintenance of blood glucose
    - primary target is liver
34
Q
  1. Carbohydrate metabolism(G)
A

glucagon stimulates breakdown of liver glycogen (not muscle) and inc. gluconeogenesis
- intravenous administration of glucagon results in rapid rise of blood glucose

35
Q
  1. Lipid Metabolism(G)
A

glucagon increases ox. of fatty acids and formation of ketone bodies from acetyl CoA

36
Q
  1. Protein metabolism(G)
A

glucagon increases uptake of a.a from the blood by liver
- Inc. C skeleton available for gluconeogenesis
- Plasma levels of a.a are decreased

37
Q

Glucagon mechanism of action

A
  • Glucagon binds to specific glucagon receptor in the cell
  • Activates adenylyl cyclase in cell membrane (inc. conc. of cAMP a second messenger for glucagon’s metabolic action)
38
Q

What does cAMP do?

A

activates cAMP-dependent kinase which phosphorylates specific protein that results in
- Inc. glycogen degradation
- Inc. gluconeogenesis
- Inc. Ketone body synthesis
- Inc. uptake of amino acids
- Dec. glycogenesis

Biochem 102 (13 decks)

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