BCH210H1 Lecture Notes - Lecture 33: Acetyl-Coa Carboxylase, Malonyl-Coa, Fatty Acid Synthase

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amethystfly536

25 May 2018

School

UTSG

Department

Biochemical Engineering and Applied Chemistry

Course

BCH210H1

Professor

Stavroula Andreopoulos

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Lecture 33: Fat Synthesis

Insulin

• Glucose → ATP (glycolysis although anabolic process because you need energy)

• Glucose → glycogen (storage in muscle or liver cell as glycolysis slows down)

• Glucose → fatty acids (how can we convert storage to synthesize fatty acid)

• As blood glucose goes up, insulin goes up; increase in fatty acid, TAGs and cholesterol synthesis

Stages in fatty acid synthesis

1. Export of mitochondrial Acetyl CoA to the cytoplasm for fat synthesis

2. Conversion of acetyl CoA to malonyl CoA via carboxylation by Acetyl-CoA carboxylase (ACC)

3. Use of malonyl CoA to form fatty acid chains by fatty acid synthase (FAS)

Citrate formation and export

• Two way usage of citrate

- Acetyl CoA + oxaloacetate → citrate to supply energy in CREB

- Export citrate into cytoplasm to convert back to Acetyl CoA to synthesize fat

• Acetyl CoA from

- Production from pyruvate in PDC (glucose)

- Fatty acid chains broken down to form acetyl CoA

- Amino acids metabolized

Citrate metabolism in cytoplasm

• Citrate converted to oxaloacetate, acetyl CoA released

• Oxaloacetate converted to malate with NADH

• Malate converted to pyruvate (release of NADPH) and pyruvate transported back in

Citrate-malate-pyruvate shuttle

• Acetyl CoA cannot cross the inner mitochondrial membrane (2 pools of CoA)

• Citrate synthase converts acetyl CoA and oxaloacetate to citrate, which crosses the inner membrane

• ATP-citrate lyase breaks down citrate to reform acetyl CoA and oxaloacetate

• Oxaloacetate (+NADH) → Malate → Pyruvate (+NADPH)

• Pyruvate can return to the mitochondria

• Lots of NADH inhibits CREB, build up of citrate, exported into cytoplasm through transporter

• Acetyl CoA can be used for fat synthesis

• Carnitine for import, citrate for export

(Anabolic) Fatty acid synthesis

• Acyl chain synthesis occurs in the cytoplasm

• 2 enzymes are needed – Acetyl CoA Carboxylase and Fatty Acid Synthase

• Acetyl CoA Carboxylase is the committed and regulated step for fatty acid synthesis

• Acetyl CoA Carboxylase, Acetyl CoA → malonyl CoA, 2C carrying precursor for fatty acid synthesis (elongation)

• Acetyl CoA Carboxylase uses 1 ATP, while Fatty Acid Synthase uses NADPH as reducing power

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BCH210H1 Full Course Notes

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Document Summary

Citrate formation and export: two way usage of citrate. Acetyl coa + oxaloacetate citrate to supply energy in creb. Export citrate into cytoplasm to convert back to acetyl coa to synthesize fat: acetyl coa from. Fatty acid chains broken down to form acetyl coa. Citrate metabolism in cytoplasm: citrate converted to oxaloacetate, acetyl coa released, oxaloacetate converted to malate with nadh, malate converted to pyruvate (release of nadph) and pyruvate transported back in. Insulin signalling activates protein phosphatase 2a to dephosphorylate fatty acid synthesis. If we have high levels of citrate, we can partially activate acc. This means a lot of acetyl coa still can make fatty acids: can still make fatty acid chains when glucagon signaling (starving) occurs but high levels of acetyl coa must be present (from proteins, etc) Review regulation: acc is the committed step for fa synthesis, acc is inhibited by phosphorylation with rising glucagon/epinephrine and amp.

Related Questions

1. Integrated metabolism

A. A molecule of glucose that you eat can eventually be transformed into part of a fatty acid that you store. Circle the pathways/cycles below that are part of this overall flow of carbon atoms. Cross out any that are not.

Gluconeogenesis, beta-oxidation, citric acid cycle, glycolysis, urea cycle, fatty acid synthesis

B. Trace the metabolic path of this glucose molecule through the enzymes it encounters along the way to being made into fat. Write all the enzymes in the list below into the proper places in the figure below. If the enzyme is not used, write its name in a ânot used" column. If it is used, write the enzyme in the order that the carbon atoms from glucose encounter the enzymes.

Pyruvate dehydrogenase, fumarase, aldolase, lactate dehydrogenase, pyruvate kinase, acetyl CoA carboxylase, fatty acid synthase, hexokinase, carnitine acyltransferase, ATP synthase

B. What is the minimum number of glucose molecules that would be necessary to be the carbon source for synthesis of a 16-carbon fatty acid through this pathway?

C. How many net glucose can be made from one molecule of a 16-carbon fatty acid?

2. Describe each cycle/transport system (compounds, compartments, tissues) and explain its purpose:

A. citrate transport system

B. Cori cycle

C. glucose/alanine cycle

Explain the logic of these pathway regulations:

A. Phosphofructokinase, not hexokinase, is the main regulation site of glycolysis.

B. SuccinylCoA inhibits the entry of acetyl CoA into the citric acid cycle.

C. NADH inhibits pyruvate dehydrogenase.

D. Citrate inhibits the citric acid cycle and activates acetyl-CoA carboxylase.

E. Insulin leads to activation of glycogen synthase.