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Which of the following are categories of lipids?
Which of the following are categories of lipids?
What are the two most important essential fatty acids that the body cannot synthesize sufficiently and must be acquired through diet?
What are the two most important essential fatty acids that the body cannot synthesize sufficiently and must be acquired through diet?
Linoleic acid and alpha-linolenic acid
What are the major products of linoleic acid and alpha-linolenic acid?
What are the major products of linoleic acid and alpha-linolenic acid?
Arachidonic acid and docosahexaenoic acid
What are the two major forms of triacylglycerol synthesis in the brain?
What are the two major forms of triacylglycerol synthesis in the brain?
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What are the two most common precursors for phospholipid synthesis?
What are the two most common precursors for phospholipid synthesis?
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What are the two major pathways through which phosphatidylcholines are synthesized?
What are the two major pathways through which phosphatidylcholines are synthesized?
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What is the rate-limiting step of cholesterol synthesis and what enzyme catalyzes this step?
What is the rate-limiting step of cholesterol synthesis and what enzyme catalyzes this step?
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What are the two biosynthetic pathways that cholesterol synthesis can diverge into?
What are the two biosynthetic pathways that cholesterol synthesis can diverge into?
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What is the typical structure of a sphingolipid?
What is the typical structure of a sphingolipid?
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What are the three major ketone bodies?
What are the three major ketone bodies?
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Which of the following are the lipid classes involved in the formation of cellular structural machinery?
Which of the following are the lipid classes involved in the formation of cellular structural machinery?
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What is the most abundant phospholipid in cell membranes?
What is the most abundant phospholipid in cell membranes?
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What is the major constituent of mitochondrial membranes?
What is the major constituent of mitochondrial membranes?
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What is the major form of sterol lipid in all mammals?
What is the major form of sterol lipid in all mammals?
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Dietary sources of cholesterol account for as much as 70% of total body cholesterol.
Dietary sources of cholesterol account for as much as 70% of total body cholesterol.
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What is the rate-limiting step of cholesterol synthesis and how is it regulated?
What is the rate-limiting step of cholesterol synthesis and how is it regulated?
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The brain synthesizes cholesterol through both the Kandutsch-Russell and the Bloch pathways, depending on neuronal tissue.
The brain synthesizes cholesterol through both the Kandutsch-Russell and the Bloch pathways, depending on neuronal tissue.
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What is the role of cholesterol in cellular membranes?
What is the role of cholesterol in cellular membranes?
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What are the major forms of endocannabinoids found in the brain?
What are the major forms of endocannabinoids found in the brain?
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What is the role of diacylglycerol in cell signaling?
What is the role of diacylglycerol in cell signaling?
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What are the three major classes of bioactive lipids found in the brain?
What are the three major classes of bioactive lipids found in the brain?
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What are the two major PUFAs found in the brain?
What are the two major PUFAs found in the brain?
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The brain relies almost entirely on glucose metabolism to meet its energy requirements.
The brain relies almost entirely on glucose metabolism to meet its energy requirements.
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What is the major energy source for the brain?
What is the major energy source for the brain?
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The amount of ATP generated from the oxidation of one molecule of glucose is greater than that generated from the oxidation of one molecule of palmitate.
The amount of ATP generated from the oxidation of one molecule of glucose is greater than that generated from the oxidation of one molecule of palmitate.
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The brain is an anaerobic organ.
The brain is an anaerobic organ.
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What is the rate-limiting step of fatty acid oxidation?
What is the rate-limiting step of fatty acid oxidation?
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The four reactions of the mitochondrial beta-oxidation pathway are catalyzed by four different enzymes.
The four reactions of the mitochondrial beta-oxidation pathway are catalyzed by four different enzymes.
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The brain is particularly vulnerable to oxidative stress.
The brain is particularly vulnerable to oxidative stress.
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What is the major form of energy produced in the brain through fatty acid oxidation?
What is the major form of energy produced in the brain through fatty acid oxidation?
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The brain can only use glucose as an energy source.
The brain can only use glucose as an energy source.
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The mitochondrial beta-oxidation pathway can only utilize even numbered carbon chains.
The mitochondrial beta-oxidation pathway can only utilize even numbered carbon chains.
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The beta-oxidation pathway is the primary source of ketone bodies.
The beta-oxidation pathway is the primary source of ketone bodies.
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Ketone bodies are predominantly shuttled into the brain in conditions of low glucose.
Ketone bodies are predominantly shuttled into the brain in conditions of low glucose.
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Mitochondrial beta-oxidation is the rate-limiting step in fatty acid oxidation.
Mitochondrial beta-oxidation is the rate-limiting step in fatty acid oxidation.
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How does the brain utilize ketone bodies for energy?
How does the brain utilize ketone bodies for energy?
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Mitochondrial beta-oxidation produces ATP
Mitochondrial beta-oxidation produces ATP
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There is a direct correlation between lipid metabolism and oxidative stress.
There is a direct correlation between lipid metabolism and oxidative stress.
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The brain is significantly affected by free radical damage.
The brain is significantly affected by free radical damage.
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Which of the following are cellular processes significantly affected by the reactive oxygen species produced through fatty acid oxidation?
Which of the following are cellular processes significantly affected by the reactive oxygen species produced through fatty acid oxidation?
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The brain is well equipped to deal with oxidative stress.
The brain is well equipped to deal with oxidative stress.
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The rate of oxidative stress and lipid peroxidation are increased in ALS.
The rate of oxidative stress and lipid peroxidation are increased in ALS.
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In ALS, the brain is unable to switch from glucose to lipid metabolism.
In ALS, the brain is unable to switch from glucose to lipid metabolism.
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The central nervous system is a much more efficient energy user than skeletal muscle.
The central nervous system is a much more efficient energy user than skeletal muscle.
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In ALS, the brain and spinal cord exhibit significantly decreased membrane fluidity.
In ALS, the brain and spinal cord exhibit significantly decreased membrane fluidity.
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The decrease in membrane fluidity in ALS is due to decreased phosphatidylinositol levels.
The decrease in membrane fluidity in ALS is due to decreased phosphatidylinositol levels.
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In ALS, there are significant changes in lipid raft composition.
In ALS, there are significant changes in lipid raft composition.
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In ALS, mitochondrial dysfunction is caused by increased oxidative stress.
In ALS, mitochondrial dysfunction is caused by increased oxidative stress.
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In ALS, increased levels of lipid peroxidation are only found in skeletal muscle.
In ALS, increased levels of lipid peroxidation are only found in skeletal muscle.
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Study Notes
Neuronal Lipid Metabolism
- Lipids are a fundamental class of organic molecules
- They are broadly classified into five categories: fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids, and sphingolipids
- Different lipid classes have diverse roles in neuronal cell populations
- They can be used as energy substrates, structural components, bioactive molecules, or a combination of these
Lipid Synthesis, Structure, and Transport
- Fatty acid synthesis primarily occurs in the endoplasmic reticulum (ER)
- It involves a cyclical process of condensation, reduction, dehydration, and reduction reactions, adding two carbons to the growing fatty acid chain
- Fatty acid synthesis uses malonyl CoA as a carbon donor
- Fatty acids can be modified through desaturation, adding double bonds, altering physical properties
- Fatty acids are transported through the bloodstream, typically bound to albumin
- Transport of fatty acids into the brain occurs via passive diffusion or transport protein mediation using mechanisms such as Fatty acid transport protein (FATP), fatty acid translocase, and caveolae
Triacylglycerol (TAG)
- TAGs are composed of a glycerol backbone with three fatty acid chains
- Fatty acid chain variation leads to different TAG properties
- TAG synthesis occurs primarily in adipose tissue and liver, and also in the brain
- The glycerol-3-phosphate pathway and the monoacylglycerol pathway are two main TAG synthesis mechanisms
- Lipolysis (TAG breakdown) is important for delivering free fatty acids to different tissues
- Lipolysis is mainly done in adipose tissue by enzymes such as adipose triglyceride lipase (ATGL).
Phospholipids
- Phospholipids are essential for various cellular processes, particularly in the brain
- They have a hydrophilic head group and hydrophobic fatty acid tails (amphipathic)
- Glycerophospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine) and phosphosphingolipids are two main groups
- Phospholipids are synthesized in the ER via multiple pathways like the CDP-choline pathway
Phospholipid Transport
- Phospholipids are transported via soluble transport proteins, vesicular transport, and close membrane contact
- Some specific transfer proteins (e.g., PC-TP, PITPα, PITPB) are involved
- Vesicular transport, where vesicles fuse with each other, and membrane contact transfer are other modes of transport
Sterol Lipids
- Cholesterol is the most abundant sterol lipid in mammals
- It has a tetracyclic ring structure with a hydroxyl group at one end (amphipathic)
- Cholesterol synthesis occurs via the mevalonate pathway
- The rate-limiting step is HMG-CoA reductase
- The synthesis pathways diverge into Kandutsch-Russell and Bloch pathways depending on the neuronal tissue
Sterol Lipid Transport
- Cholesterol is transported through the body via lipoproteins such as VLDL and LDL
- Cholesterol can be incorporated into cellular membranes or esterified through other mechanisms in order to be transported into and out of the brain
Sphingolipids
- Sphingolipids have a sphingosine backbone
- Ceramides, sphingomyelins, and glycosphingolipids (e.g., glucosylceramide, galactosylceramide) are important subclasses
- Sphingolipids form a crucial part of the plasma membrane
- Sphingolipid synthesis occurs in the ER, progressing to more locations
- Sphingolipids are transported primarily via ceramide transport proteins like CERT, and vesicular transport
Lipids as Energy Substrates
- The brain relies on glucose metabolism for energy
- Approximately 20% of the brain's energy requirement may come from fatty acid oxidation
- During fasting, ketone bodies (acetoacetate, D-3-hydroxybutyrate, propanone) are produced as an alternative energy source, primarily in the liver.
Mitochondrial Beta-Oxidation
- Fatty acids are activated into fatty acyl-CoAs through acyl-CoA synthases
- The activated fatty acids are transported to the mitochondrial matrix via the carnitine shuttle system
- The fatty acyl-CoAs undergo a cycle of four reactions
- Each cycle shortens the fatty acid chain by two carbons, generates FADH2, NADH, and acetyl-CoA, producing ATP through the electron transport chain
Peroxisomal Beta-Oxidation
- Peroxisomes can oxidize branched and very long-chain fatty acids
- They produce H2O2 as a byproduct and use different enzymes, compared to mitochondrial beta-oxidation
Lipid Metabolism in ALS
- ALS is associated with lipid handling alterations and lipid dysfunction, potentially causing energy substrate dysregulation, structural damage and signaling disruptions in neurons and muscle.
- SOD1 mutation, for example is linked to oxidative stress, suggesting other potential mechanisms for lipid dysregulation in patients
Targeting Lipid Metabolism for ALS
- Treatments aimed at correcting the lipid metabolism dysregulation may potentially offer benefits for ALS patients
- Some strategies include high-calorie, high-protein diets, ketogenic diets, and dichloroacetate treatments.
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Description
This quiz explores the fundamental aspects of neuronal lipid metabolism, including classifications of lipids, their roles in neuronal cells, and the process of fatty acid synthesis. Additionally, it examines the transport mechanisms of fatty acids essential for brain function.
