1.10 - Anabolism Flashcards

1
Q

What are the five general components of anabolism?

A

Costly: therefore need a source of energy (ATP)
Reductive Process: therefore need reducing agents (NADPH)
Need a carbon source (Acetyl-CoA and Amino Acids)
Optional nitrogen source (Amino-Acids & Nucleotides)
Various enzymes required

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2
Q

Describe Fatty Acid Synthesis

A

Formation of 16-18 carbon acyl chains
Precursor molecule is acetyl-CoA
Pathway is localized to the cytosol (acetyl-CoA shuttled out)
Like β-oxidation the pathway is a repeating set of reactions, in order to keep building a long acyl-chain. 2-carbon atoms are added per cycle. Reverse of β-oxidation
Reactions occur in a multi sub-unit enzyme called fatty acid synthase

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3
Q

Describe the signal for production of FAs

A

Build up of [citrate] (TCA Cycle) indicates cell is in a high energy state as in a high energy state the high [NADH] & [ATP] blocks the TCA cycle after the formation of citrate and the [citrate] increases. When this reaches a critical point, citrate is moved out of the mitochondria by a transporter.

The citrate in the cytoplasm is then broken back down to OAA and Acetyl-CoA.
OAA is converted to malate (TCA cycle intermediate) –> re-enters the mitochondria –> enters the TCA cycle

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4
Q

Describe the commitment of Acetyl-Coa to FA synthesis

A

Acetyl-CoA has a large number of cellular fates
Funnelling it towards FA synthesis requires commitment
1st step in the pathway provides this (because of the energy utilisation)
Acetyl-CoA is converted to Malonyl-CoA
Catalysed by acetyl-CoA carboxylase
Highly regulated enzyme

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5
Q

What is the first reaction in the commitment of AcetylCoA to FA synthesis?

A

AcetylCoA + CO2 + ATP –> MalonylCoA + ADP + Pi

Enzyme: AcetylCoA Carboxylase

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6
Q

Describe the regulation of the first step in the commitment of AcetylCoA to FA synthesis?

A

Although citrate is converted to Acetyl-CoA, it also stimulates the reaction
Glucagon will inhibit this reaction as it is released in low energy states.

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7
Q

What are the reactions of FA Synthesis

A
  1. Transfer: MalonylCoA + Acyl Carrier Protein(ACP)
  2. Condenstaion: joining of two Acetyl-ACPs if first synthesis of growing chain, or Acetyl-ACP to the growing acyl chain
  3. Reduction
  4. Dehydration
  5. Reduction
  6. Re-setting: Resumption of cycle with “fresh” Malonyl-CoA
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8
Q

Compare FA Anabolism & Catabolism with regards to:

  • Location
  • Reactant
  • Acyl Carrier
  • Enzyme Organisation
  • Redox Carriers
  • Allosteric Control
  • Hormonal Control
  • Product
A
Location
   - Anabolism: Cytosol
   - Catabolism: Mitochondria
Reactant
   - Anabolism: Acetyl CoA (Malonyl-CoA)
   - Catabolism: C14-C18 Acyl Chains
Acyl Carrier
   - Anabolism: ACP
   - Catabolism: CoASH
Enzyme Organisation
   - Anabolism: Single Complex
   - Catabolism: Non Associated
Redox Carriers
   - Anabolism: NADPH
   - Catabolism: NAD+ & FAD
Allosteric Control
   - Anabolism: Citrate increased, PalmitoylCoA decreased
   - Catabolism: MalonylCoA (decreased carnitine transferase)
Hormonal Control
   - Anabolism: Insuline - increased AcetylCoA carboxylase. Glucagon - decreased acetylCoA carboxylase
   - Catabolism: Glucagon (Increased TAG lipase)
Product
   - Anabolism: Palmitate (common FA)
   - Catabolism: AcetylCoA
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9
Q

List the overall regulation of Lipid Metabolism

A
Glucagon (catabolic)
  o Stimulates Lipases
  o Inhibits Acetyl-CoA Carboxylase
Insulin (Anabolic)
  o Stimulates Acetyl CoA Carboxylase
Citrate
  o Stimulates Acetyl-CoA Carboxylase
16 carbon fatty acids
  o Inhibit Acetyl-CoA Carboxylase
Malonyl CoA
  o Inhibits Carnitine Acyl Transferase --> want to stop the breakdown of FA.
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10
Q

Why is Glucose synthesis so important?

A

Brain, nervous system, RBCs, testes, renal medulla and embryonic tissue all use glucose as sole or major source of fuel

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11
Q

What are some of the precursors for glucose synthesis?

A

Lactate, Pyruvate, glycerol, and some amino acids

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12
Q

Where does glucose synthesis occur?

A

Predominantly in the liver, with a small amount in the renal cortex

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13
Q

Describe glucose synthesis

A

Known as Gluconeogenesis
Require reducing power –> Delivered by NADH
Energetically expensive pathway –> 4 ATP and 2 NADH needed per molecule of glucose produced
Occurs primarily in the liver, with some in the renal cortex but none in the brain, skeletal muscle or cardiac muscle –> more evidence for the altruism of the liver

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14
Q

Describe the reactions of gluconeogenesis as they compare to those in glycolysis

A

Many reactions are identical to glycolysis but in reverse

Some of the reactions however are kinetically unfavourable so use bypasses instead

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15
Q

Describe the Pyruvate –> PEP in gluconeogenesis

A
Pyr --> PEP is not possible
"By pass Reactions used instead
Carboxylation of Pyruvate to OAA
OAA moved to cytosol
Decarboxylation to PEP
Uses ATP
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16
Q

What are some of the generalised types of regulation of metabolic pathways?

A
Generalised
  - Compartmentalisation of pathways
  - Target rate-limiting or branch point enzymes
  - Substrate supply
  - Feed back/forward stimuli
Hormonal
  - Whole body homeostasis
  - Rapid: Signal transfuction
  - Slow: Protein expression
Redox State
  - Rapid regulatory phase
  - Dictated by energy need or balance
  - [ATP]/[ADP] and [NADH]/[NAD+]
17
Q

What are the catabolic hormonal controls of glucose metabolism?

A

Glucagon: released by alpha cells of the pancreas and acts on the liver
Adrenaline: Released by the adrenal medulla and acts on peripheral tissues (especially muscle)
Both lead to mobilisation of glucose stores & utilisation by glycolysis

18
Q

What is an example of an anabolic hormonal control of glucose metabolism

A

Insulin
Peptide released by beta cells of the pancreas –> general anabolic signal (formation of macromolecules)
Promotes glycogen synthesis
Stimulates glucose synthesis and prevents its breakdown

19
Q

Describe a reciprocal regulation mechanism on glucose metabolism

A

High flux of glucose in will lead to increased [F6P]. This will produce a little bit of F2,6bP. This will then stimulate PFK1 to bring F6P down glycolysis pathway and not up through gluconeogenesis.

F2,6bP is the most powerful allosteric regulator of glucose metabolism/anabolism. It stimulates glycolysis and inhibits gluconeogenesis. The little loop to produce F2,6bP only occurs when there is lots of F6P

20
Q

What are the major effects of Insulin in regulating glucose metabolism

A

Stimulates glycolysis
Stimulates glycogen synthesis
Inhibits gluconeogenesis
Inhibits glycogenolysis

21
Q

What are the major effects of glucagon in regulating glucose metabolism

A

Activates glycogenolysis
Activates gluconeogenesis (hepatic)
Inhibits glycogen synthesis
Inhibits glycolysis (hepatic)