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
What are some of the generalised types of regulation of metabolic pathways?
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+]
What are the catabolic hormonal controls of glucose metabolism?
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
What is an example of an anabolic hormonal control of glucose metabolism
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
Describe a reciprocal regulation mechanism on glucose metabolism
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
What are the major effects of Insulin in regulating glucose metabolism
Stimulates glycolysis
Stimulates glycogen synthesis
Inhibits gluconeogenesis
Inhibits glycogenolysis
What are the major effects of glucagon in regulating glucose metabolism
Activates glycogenolysis
Activates gluconeogenesis (hepatic)
Inhibits glycogen synthesis
Inhibits glycolysis (hepatic)
