Lipogenesis: Fatty Acid Synthesis

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Questions and Answers

What is the primary source of fatty acids used by the body?

Glycogen breakdown

De novo lipogenesis

Diet (correct)

Protein degradation

Where does the de novo synthesis of fatty acids take place?

Mitochondria

Cytosol (correct)

Endoplasmic reticulum

Golgi apparatus

What is the role of HCO3 in lipogenesis?

End product

Cofactor

Substrate

Source of CO2 (correct)

Which of the following tissues is NOT a primary site for fatty acid synthesis?

Skeletal muscle Signup and view all the answers

What is the primary purpose of de novo lipogenesis in the body?

To store excess energy from carbohydrates and proteins as fatty acids Signup and view all the answers

What is the end product of de novo lipogenesis?

Palmitate Signup and view all the answers

What is the purpose of citrate in regulating Acetyl CoA carboxylase?

To allosterically activate the enzyme Signup and view all the answers

Which kinase is activated by cyclic AMP (cAMP)–dependent protein kinase A (PKA)?

One of the AMPK kinases Signup and view all the answers

What happens to Acetyl CoA carboxylase in the presence of insulin?

It is dephosphorylated and active Signup and view all the answers

What is the effect of a high-fat, low-carbohydrate diet on Acetyl CoA carboxylase synthesis?

It decreases ACC synthesis Signup and view all the answers

What is the role of Adenosine monophosphate–activated protein kinase (AMPK) in regulating Acetyl CoA carboxylase?

It phosphorylates and inactivates ACC Signup and view all the answers

What is the transcription factor that upregulates Acetyl CoA carboxylase synthesis in response to carbohydrate, specifically glucose?

Carbohydrate response element–binding protein Signup and view all the answers

What is the primary mechanism by which metformin lowers plasma TAG?

Activation of AMPK Signup and view all the answers

What is the role of 4'-phosphopantetheine in fatty acid synthesis?

It carries acyl units on its terminal thiol group and presents them to the catalytic domains of FAS Signup and view all the answers

How many NADPH molecules are required for the synthesis of one molecule of palmitate?

14 NADPH Signup and view all the answers

What is the primary source of NADPH for fatty acid synthesis?

Pentose phosphate pathway Signup and view all the answers

What is the function of AMPK in the treatment of type 2 diabetes?

Increase of glucose uptake in muscle Signup and view all the answers

What is the function of the acyl carrier protein (ACP) domain in FAS?

It carries acyl units on its terminal thiol group Signup and view all the answers

What is the byproduct of cytosolic conversion of malate to pyruvate?

CO2 and NADPH Signup and view all the answers

What is the source of cytosolic NADH required for the reduction of OAA to malate?

Glycolysis Signup and view all the answers

What is the function of ATP citrate lyase?

To convert citrate to oxaloacetate Signup and view all the answers

What is the primary end product of fatty acid synthase activity?

Palmitic acid (16:0) Signup and view all the answers

What is the function of fatty acyl CoA desaturases?

To desaturate LCFA by adding cis double bonds Signup and view all the answers

Where does the elongation of VLCFAs over 22 carbons occur?

Brain Signup and view all the answers

What is the primary product of the first double bond insertion in fatty acid desaturation reactions?

Oleic acid, 18:1(9) Signup and view all the answers

What is the functional group involved in the esterification of fatty acids to glycerol?

Carboxyl group Signup and view all the answers

Why are polyunsaturated ω-6 linoleic acid and ω-3 linolenic acid considered nutritionally essential?

Humans cannot introduce double bonds from carbon 10 to the ω end of the chain Signup and view all the answers

What is the term for an acylglycerol that is solid at room temperature?

Fat Signup and view all the answers

What is the direction of numbering of carbon atoms in fatty acids, when starting from the methyl end?

ω—1,2,3, etc. Signup and view all the answers

What is the direction of numbering of carbon atoms in fatty acids, when starting from the COOH group?

C1, C2, etc. Signup and view all the answers

Study Notes

Lipogenesis (De Novo Synthesis of Fatty Acids)

Lipogenesis occurs in the cytosol of many tissues, including liver, kidney, brain, lung, mammary gland, and adipose tissue
Fatty acid synthesis occurs primarily in liver and lactating mammary glands
Lipogenesis necessitates substrate: Acetyl CoA, cofactors: NADPH, ATP, Mn2+, Biotin, and source of CO2: HCO3 (Bicarbonate)
End product: Palmitate (Palmitic acid), a free fatty acid

Acetyl CoA Carboxylase (ACC) Regulation

ACC is the rate-limiting and regulated step in fatty acid synthesis
Allosterically activated by citrate, and allosterically inactivated by palmitoyl CoA (the end product of the pathway)
Reversible phosphorylation by AMP-activated protein kinase (AMPK) and covalent phosphorylation by PKA
In the presence of hormones like epinephrine and glucagon, ACC is phosphorylated and inactive, while in the presence of insulin, ACC is dephosphorylated and active

Fatty Acid Synthase (FAS)

Catalyzes the remaining series of reactions in fatty acid synthesis
Multifunctional enzyme with 6 different enzymic domains plus a 4'-phosphopantetheine-containing acyl carrier protein (ACP) domain
Process involves the addition of 2 carbons from malonyl CoA to the carboxyl end of a series of acyl acceptors

Reductant Sources for Fatty Acid Synthesis

One palmitate synthesis requires 14 NADPH, a reductant (reducing agent)
Pentose phosphate pathway is a major supplier of NADPH
Cytosolic conversion of malate to pyruvate, in which malate is oxidized and decarboxylated by cytosolic malic enzyme (NADP+-dependent malate dehydrogenase), also produces cytosolic NADPH (and CO2)

Interrelationship between Glucose Metabolism and Palmitate Synthesis

Pyruvate carboxylase and pyruvate dehydrogenase are involved in the interrelationship between glucose metabolism and palmitate synthesis

Elongation of Fatty Acids

Palmitic acid can be further elongated by addition of 2 carbon units to the carboxylate end in smooth endoplasmic reticulum
Elongation requires a system of separate enzymes rather than a multifunctional enzyme
Brain has additional elongation capabilities, producing very long chain fatty acids (VLCFAs) over 22 carbons

Chain Desaturation

Fatty acyl CoA desaturases are present in smooth endoplasmic reticulum (SER)
Desaturation reactions require oxygen, NADH, cytochrome b5, and its FAD-linked reductase
The first double bond is typically inserted between carbons 9 and 10, producing primarily oleic acid, 18:1(9), and small amounts of palmitoleic acid, 16:1(9)

Triacylglycerol Synthesis and Storage

Mono-, di-, and triacylglycerols consist of one, two, or three molecules of fatty acid esterified to a molecule of glycerol
Fatty acids are esterified through their carboxyl groups, resulting in a loss of negative charge and formation of neutral fat
An acylglycerol that is solid at room temperature is called a fat

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Description

Test your knowledge of lipogenesis, including its characteristics, reaction steps, regulation, and interrelationship with glucose metabolism. Learn about the synthesis of fatty acids, their elongation and desaturation, and the role of glycerol 3-phosphate and triacylglycerol.