L2 - Overview of metabolic regulation and integration Flashcards

1
Q

Core concepts in metabolic integration

A

1 - Multiple regulatory mechanisms can target a single protein
2 - Single pathway can be regulated at multiple steps (often by different mechanisms)
3 - Control of one protein can have secondary actions

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2
Q

Regulation of opposing pathways: how is it managed without wastefully synthesising and degrading substances and what enzymes must be present for this process?

A

Reciprocal regulation of opposing pathways occurs - when one pathway is increased the other is reduced

Would not be possible if both pathways were catalysed by the same enzymes - at least one step is catalysed by different enzymes in the catabolic and anabolic directions – regulated separately

Opposing catabolic and anabolic pathways may also occur in different subcellular compartments

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3
Q

Pancreas: what is it, what part of it secretes hormones, and what is the pathway of secreted hormones?

A

Organ that secretes hormones in response to blood glucose levels

Islets of Langerhans (α/β cells)

Hormones released into the hepatic portal vein – first transported to liver and adipose tissue

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4
Q

Brain

A

Integrates inputs from surroundings and sends signals to other parts of the body

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5
Q

Liver

A
  • Processes fats, carbohydrates, and proteins from the diet
  • Synthesises and distributes lipids, ketones, and glucose
  • Converts excess nitrogen into urea
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6
Q

Lymphatic system

A

Carries lipids from intestines to liver

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7
Q

Adipose tissue

A
  • Synthesises, stores, and mobilises triacylglycerols
  • Brown adipose tissue carries out thermogenesis
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8
Q

Skeletal muscle

A

Uses ATP to contract muscles, resulting in movement

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9
Q

Cardiac muscle

A

Uses ATP to pump blood around the body

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10
Q

Portal vein

A

Carries nutrients from intestine to liver

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11
Q

Small intestine

A

Absorbs nutrients from the diet and transports them into either circulatory or lymphatic system

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12
Q

Hormonal regulation of metabolism

A

Hormones are carried by the bloodstream to nearby cells or more distant tissues/organs - bringing about metabolic changes in target cells

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13
Q

Insulin: what is it, when is it released, and what does it do?

A

Peptide hormone

Released by pancreatic β-cells in response to high blood glucose levels

  • Stimulates glucose transport into cells
  • Stimulates synthesis of fat, glycogen and protein
  • Inhibits the breakdown of fat, glycogen and protein
  • Essentially causes a coordinated change in metabolism
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14
Q

Glucagon: what is it, when is it released, what does it target, and what does it do?

A

Peptide hormone

Released by pancreatic α-cells in response to low blood glucose

Liver, primarily

  • Inhibits synthesis of fat, glycogen and protein
  • Stimulates breakdown of fat, glycogen and protein
  • Promotes mobilisation of fuel storage
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15
Q

Epinephrine: what is it, when is it released, what does it target, and what does it do?

A

Tyrosine-derived peptide hormone (?)

Released by adrenal medulla in response to ‘stress’ (fear, pain, starvation)

Target tissues: muscle, adipose tissue, liver

  • Inhibits synthesis of fat, glycogen and protein
  • Stimulates breakdown of fat, glycogen and protein
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16
Q

Glucose signalling: how it causes insulin production

A
  • Glucose enters pancreatic beta-cells through the glucose transporter - GLUT2
  • Glucose then gets broken down via glycolysis and the citric acid cycle to produce ATP
  • ATP binds to ATP-gated K⁺ channels, inhibiting them and causing depolarisation
  • Depolarisation causes opening of voltage-gated Ca²⁺ channels, resulting in a Ca²⁺ influx
  • Ca²⁺ interacts with insulin granules at the endoplasmic reticulum and causes fusion of vesicles with the plasma membrane, resulting in the secretion of insulin
17
Q

Glucagon signalling: how it enters cells

A
  • Binds to receptor (GPCR)
  • Gs causes adenyl cyclase to be produced
  • ATP is converted to cyclic AMP by adenyl cyclase
  • cAMP activates protein kinase A
18
Q

Epinephrine signalling: how it enters cells

A
  • Binds to receptor (GPCR)
  • Gs causes adenyl cyclase to be produced
  • ATP is converted to cyclic AMP by adenyl cyclase
  • cAMP activates protein kinase A
19
Q

Typical intracellular messengers

A

cAMP, Ca²⁺, IP₃, etc

20
Q

Insulin: how does it send signals to cells and what is the process for it?

A

Using tyrosine kinase receptor

  • Insulin receptor binds insulin and autophosphorylates on its C-terminus tyrosine residues
  • Insulin receptor’s tyrosine residues are used to phosphorylate insulin receptor substrates (IRS-1)

IRS-1 can then activate PKB/Akt or MAPK to undergo activating various processes

21
Q

PKB/Akt: what is it, what is it activated by, and what does it do?

A

Protein kinase B

Insulin/IRS-1

  • Phosphorylation of metabolic enzymes (to increase/decrease activity)
  • Transcription factors (control of gene expression)
  • Activate other regulatory proteins (e.g. phosphatases, translation factors, glucose transporter trafficking)
22
Q

MAPK: what is it, what is it activated by, and what does it act upon?

A

Mitogen-activated protein kinase

Insulin/IRS-1

Transcription factors

23
Q

cAMP: what is it and what does it do?

A

Cyclic adenosine monophosphate

  • Affects gene expression
  • Activates cAMP response element binding protein (CREBP)
24
Q

PKA: what is it and what does it do?

A

Protein kinase A

  • Stimulates gluconeogenesis - Activates FBPase-2, Inhibits pyruvate kinase, and Activates PEP CK
  • Stimulates glycogen breakdown - activates glycogen phosphorylase
  • Inhibits glycogen synthesis - inhibits glycogen synthase
  • Stimulates triacylglycerol (TAG) synthesis - activates HSL, ATGL, and perilipin
  • Stimulates FA-oxidation/inhibits FA synthesis - inhibits ACC
25
ATP/AMP as allosteric effectors: what are the typical cellular concentrations of them and why is there a massive difference in potency between them?
ATP ~ 5mM AMP ~ 0.1mM A 10% decrease in [ATP] can greatly affect the activity of ATP utilizing enzymes but results in a 600% increase in [AMP] - AMP can be a more potent allosteric effector (10% of 5mM is 0.5mM, 0.1->0.6mM is a 600% increase )
26
AMPK: what is it, what is it activated by, and what does it do?
AMP-dependent protein kinase * Increased cellular [AMP] * Reduced nutrient supply * Increased exercise * Sympathetic nervous system * Leptin, adiponectin, etc Acts as an ‘energy sensor’, has varying functions in different tissues but the effects lead to the same, main function: Coordinated change to shift metabolism away from energy processes and increases energy generation by using catabolic pathways
27
MAPK in the heart
Stimulates: * Fatty acid oxidation * Glucose uptake * Glycolysis
28
MAPK in the brain
Stimulates: * The desire to eat (hunger)
29
MAPK in the liver
Inhibits: * Fatty acid synthesis * Cholesterol synthesis * Glycogen synthesis
30
MAPK in the pancreas
Inhibits: * beta-cell insulin secretion
31
MAPK in skeletal muscle
Stimulates: * Fatty acid uptake/oxidation * Glucose uptake * Mitochondrial biogenesis
32
MAPK in adipose muscle
Inhibits: * Fatty acid synthesis * Lipolysis
33
Glucokinase: what methods of regulation affect it?
* mRNA stability * Degradation * Allostery * Compartmentalisation * Transcription
34
What are the advantages of using multiple mechanisms for regulation?
* Failsafe mechanism * Different signals, different mechanisms - can be regulated by various different things * Allows different speeds of regulation (transcription, long - phosphorylation, quick) * Allows degree of regulation?