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Physiology Metabolism > Metabolism 6: Synthesis of FA and TAGs > Flashcards

Metabolism 6: Synthesis of FA and TAGs Flashcards

1
Q

What favors lipid metabolism, fed or fasting state?

A

Fed state. Insulin promotes the Acetyl-CoA Carboxylase to convert Acetyl-CoA to Fatty Acyl-CoA which can then be used to generate TAGs

This state also favors using Acetyl-CoA to form cholesterol

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2
Q

What does the fasting state favor?

A

Epinephrine drives the formation of acetyl-CoA and ketone bodies from fatty acyl-CoAs

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3
Q

How is the transportation of fatty acid diffferet in the fed and fasting states?

A

Fed State: FA transported as part of TAGs on lipoproteins to be sent with chylomicrons to muscle and adipose tissue

Fasting: FA from adipose tissue transported bound to albumin to be sent to muscle and liver for generateing ketone bodies and energy production via oxidation

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4
Q

What is Palmitic fatty Acid?

A

16:0

Product of FA synthesis

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5
Q

What is Stearic Fatty Acid ?

A

Stearic Fatty Acid
18:0
Has common chain length

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6
Q

What is linoleic fatty acid?

A

Essential fatty acid (Omega 3)

18: 2 (9,12)
18: 3(9,12,15)

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7
Q

What is arachaidonic acid?

A

Precursor of prostaglandin

20:4(5,8,11,14)

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8
Q

What is the stoichiometric reaction for fatty acid biosynthesis?

A

Acetyl-CoA + 7 Malonyl CoA + 14 NADPH + 14H+ -> Palmitate + 7 CO2 + 14 NADP + 8 CoA + 6 H2O

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9
Q

What does Acetyl-CoA Carboxylase do?

A

Forms 7 Malonyl CoA from 7 Acetyl-CoA along with 7 CO2, which later reacts with ACetyl CoA to form Palmitoyl CoA via fatty acid synthesis

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10
Q

What does fatty acid biosynthesis require?

A

Acetyl Groups: transported from mitochrondria via citrate

Acetyl-CoA CArboxylase: form malonyl CoA

Biotin: carrier of activated CO2

Fatty Acid Synthase Complex: Use 1 Acetyl CoA and 7 Malonyl CoA to synthesize even numbered saturated fatty acids

NADPH

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11
Q

Where do the carbons from fatty acid synthesis come from?

A

Acetyl CoA (ultimately)

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12
Q

What is the significance of citrate in fatty acid synthesis?

A

Used to transport acetyl groups from mitochondria to cytosol

Allosterically activates Acetyl-CoA Carboxylase

**Also used to regenerate pyruvate via covnersion to oxaloacetate after losing acetyl-CoA

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13
Q

Explain the citrate shuttle

A

Mitochondrial Matrix: Oxaloacetate and Acetyl-CoA combine via citrate synthase -> citrate formed

Citrate trasported out of mitochondria to cytosol -> ATP-Citrate lyase -> Oxaloacetate and Acetyl-CoA reformed again

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14
Q

What is the significance of Acetyl-CoA Carboxylase?

A

Rate limiting enzyme in FA biosynthesis
Catalyze formation of Malonyl CoA from Acetyl CoA

Requires biotin as a cofactor that carries activated oxygen

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15
Q

What regulates Acetyl-CoA Carboxylase?

A

Allosteric:
+: citrate
-: Palmitoyl CoA (downstream product), AMP

Hormonal
+: insulin (leads to dephosphorylation of enzyme)
-: glucagon, epinephrine (leads to phosphorylation of enzyme)

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16
Q

What is the signfiicance of Malonyl CoA?

A

It is the product of the rxn catalyzed by Acetyl-CoA Carboxylase.

It inhibits the rate limiting enzyme of fatty acid oxidation (beta ox) and ketone body formation

17
Q

What are some long term regulating factors of Acetyl CoA Carboxylase?

A

Increased Enzyme Synthesis: high carb diet, insulin, thyroid hormone

Decreased Enzyme Synthesis: High fat diet, fasting glucagon

18
Q

What is the Fatty Acid Synthase Complex (FAS)

A

7 enzyme activity complex that catalyzes the formation of fatty acids from 1 Acetyl-CoA and 7 Malonyl CoA

19
Q

What is the stoichiometric reaction carried out by FAS complex?

A

Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14H+ -> Palmitate + 7CO2 + 14 NADP + 8 CoA + 6H2O

20
Q

What happens in the first cycle of the FAS complex?

A

Acetyl-CoA combines with a 2 carbon acetyl group from Malonyl CoA to create a 4C butyryl group

21
Q

What happens in the last 6 cycles of the FAS complex?

A

a 2C acetyl group from Malonyl CoA is added to the growing fatty acid chain from the 4C Butyryl group formed from the 1st cycle untili a 16C saturated FA Palmitate is formed

22
Q

What are the 6 enzymatic steps in 1 cycle of the FAS complex?

A

Acetyl Transferase: transfer Acetyl from Acetyl-CoA to ACP => Acetyl-ACP
Malonyl Transferase: transfer malonyl from Malonyl-CoA to ACP => Malonyl-ACP

Ketoacyl Carrier Protein Synthase: CONDENSATION; Combine Acetyl-ACP and Malonyl-ACP to create acetoacetyl-ACP and CO2

Ketoacyl-ACP Reductase: REDUCTION; Reduce Acetoacetyl-ACP with NADPH to get D3hydroxybutyryl-ACP

3Hydroxyacyl-ACP Dehydratase: DEHYDRATION; Dehydrate to form crotonyl-ACP and lose water

Enoyl-ACP Reductase: REDUCTION reduce crotonyl-ACP with NADPH to get butyryl-ACP our final product

*6 more of these to get palmitic acid

23
Q

What is an allosteric regulator of the FAS complex?

A

Fructose 1,6 bisphosphate (Allosteric Activator)

24
Q

What are long term methods of regulation of the FAS complex?

A

Increased Enzyme Synthesis: high carb diet via insulin, fat free diet

Decreased Enzyme Synthesis: Glucago, High fat diet via low insulin and high fasting glucagon

25
Q

What is an example of a polyunsaturated essential fatty acid?

A

Linoleic Fatty Acid. Must be obtained from diet

26
Q

What can happen to fatty acids after they are synthesized

A

Can be elongated
Can be desaturated
Eventually they will be esterified to TAGs, phospholipids, cholesterol

27
Q

What is the primary regulator for the endogenous synthesis of TAGs?

A

Substrate availablity

28
Q

What are PPARs?

A

Peroxisome Proliferator-Activated Receptors that promote TAG deposition

29
Q

What happens to TAGs that are syntehsized in the liver?

A

Packaged into VLDL and sent out into lymph and then TAG is released into capillaries

30
Q

What happens to dietary triacylglycerols?

A

In the intestines, they are emulsified by bile acids and digested with lipase to generate fatty acid and a monoacylglycerol molecule. The monoacylglycerol is then packaged along with synthesized TAGs into lipoproteins and then into chylomicrons for transport into circulation

Physiology Metabolism (11 decks)

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