1.10 - Anabolism Flashcards
What are the five general components of anabolism?
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
Describe Fatty Acid Synthesis
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
Describe the signal for production of FAs
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
Describe the commitment of Acetyl-Coa to FA synthesis
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
What is the first reaction in the commitment of AcetylCoA to FA synthesis?
AcetylCoA + CO2 + ATP –> MalonylCoA + ADP + Pi
Enzyme: AcetylCoA Carboxylase
Describe the regulation of the first step in the commitment of AcetylCoA to FA synthesis?
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.
What are the reactions of FA Synthesis
- Transfer: MalonylCoA + Acyl Carrier Protein(ACP)
- Condenstaion: joining of two Acetyl-ACPs if first synthesis of growing chain, or Acetyl-ACP to the growing acyl chain
- Reduction
- Dehydration
- Reduction
- Re-setting: Resumption of cycle with “fresh” Malonyl-CoA
Compare FA Anabolism & Catabolism with regards to:
- Location
- Reactant
- Acyl Carrier
- Enzyme Organisation
- Redox Carriers
- Allosteric Control
- Hormonal Control
- Product
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
List the overall regulation of Lipid Metabolism
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.
Why is Glucose synthesis so important?
Brain, nervous system, RBCs, testes, renal medulla and embryonic tissue all use glucose as sole or major source of fuel
What are some of the precursors for glucose synthesis?
Lactate, Pyruvate, glycerol, and some amino acids
Where does glucose synthesis occur?
Predominantly in the liver, with a small amount in the renal cortex
Describe glucose synthesis
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
Describe the reactions of gluconeogenesis as they compare to those in glycolysis
Many reactions are identical to glycolysis but in reverse
Some of the reactions however are kinetically unfavourable so use bypasses instead
Describe the Pyruvate –> PEP in gluconeogenesis
Pyr --> PEP is not possible "By pass Reactions used instead Carboxylation of Pyruvate to OAA OAA moved to cytosol Decarboxylation to PEP Uses ATP