Comprehensive Lipid Metabolism: Synthesis, Transport, and Regulation

What are the starting materials and necessary cofactors for fatty acid synthesis?

The starting materials include acetyl-CoA, malonyl-CoA, and NADPH; the synthesis occurs in the cytoplasm.

What is the committing step for fatty acid biosynthesis, and which enzyme is involved?

The committing step is the conversion of acetyl-CoA to malonyl-CoA, catalyzed by acetyl-CoA carboxylase, which is regulated by various factors including insulin and glucagon.

Why does the synthesis of fatty acids require energy?

Fatty acid biosynthesis requires energy in the form of ATP and reducing power from NADPH, which is generated through the pentose phosphate pathway.

How does palmitate serve as a precursor for other fatty acids?

Palmitate can be elongated, desaturated, or branched to form other fatty acids; certain fatty acids are considered essential due to the absence of specific enzymes in humans.

What is the process of triglyceride biosynthesis from fatty acids?

Triglycerides are synthesized by esterifying three fatty acids to glycerol, primarily occurring in adipose tissue.

How are membrane phospholipids synthesized from fatty acids?

Membrane phospholipids are synthesized by combining fatty acids with glycerol phosphate and cytidine nucleotides, primarily in the endoplasmic reticulum.

What is the starting material for cholesterol biosynthesis?

Cholesterol biosynthesis starts from acetyl-CoA, with hydroxymethylglutaryl-CoA being a key intermediate.

What is the role of the citrate shuttle in lipid biosynthesis?

The citrate shuttle transports acetyl-CoA from the mitochondria to the cytoplasm for lipid biosynthesis, facilitating the conversion of carbohydrates to lipids.

How is phytanic acid degraded?

Phytanic acid is degraded through α-oxidation followed by β-oxidation; defects in α-oxidation can lead to Refsum disease.

What is the major function of chylomicrons?

Chylomicrons transport dietary triglycerides and cholesterol from the intestines to adipose tissue and the liver.

What are the primary components of very-low-density lipoproteins (VLDL)?

VLDL primarily contains triglycerides, cholesterol, and apolipoproteins, functioning mainly to transport endogenous triglycerides.

What is the main role of low-density lipoproteins (LDL)?

LDL primarily transports cholesterol esters to various tissues in the body.

What distinguishes high-density lipoproteins (HDL) from other lipoproteins?

HDL has a higher proportion of protein compared to other lipoproteins and is involved in the removal of cholesterol from tissues.

What are the major apolipoproteins associated with chylomicrons?

Chylomicrons contain apolipoprotein B-48, apo C-I, apo C-II, apo C-III, and apo E.

What is the significance of bile in lipid digestion?

Bile emulsifies dietary lipids, forming micelles that facilitate the digestion and absorption of lipids in the intestine.

What enzymes are involved in the hydrolysis of triglycerides during digestion?

Pancreatic lipase, cholesteryl esterase, and phospholipase are the key enzymes that hydrolyze triglycerides, cholesterol esters, and phospholipids.

How are lipoproteins structured?

Lipoproteins have a core of nonpolar lipids surrounded by a monolayer of phospholipids and proteins, facilitating lipid transport in the bloodstream.

What is the density range of chylomicrons?

Chylomicrons have a density of less than 0.94 g/mL.

What is the role of apolipoproteins in lipoproteins?

Apolipoproteins help solubilize lipids and provide recognition features for directing lipoprotein particles to cellular targets.

What is the primary lipid component of HDL?

HDL is primarily composed of phospholipids and cholesterol esters.

How does the body absorb dietary lipids?

Dietary lipids are absorbed through mucosal cells via passive diffusion after being emulsified by bile and hydrolyzed by enzymes.

What is the relationship between circulating cholesterol levels and health?

High circulating cholesterol levels are associated with an increased risk of diseases of the circulatory system.

What is atherosclerosis?

A condition characterized by the accumulation of arterial plaques, leading to hardening of the arteries.

What is the role of LDL in the body?

LDL, or low-density lipoprotein, is involved in lipid transport but is often referred to as 'bad cholesterol' due to its association with coronary heart disease.

What is the function of HDL?

HDL, or high-density lipoprotein, helps remove cholesterol from arterial walls, reducing the risk of atherosclerosis, hence called 'good cholesterol.'

How do dietary lipids enter the circulation?

Dietary lipids enter the circulation as chylomicrons, which are formed and secreted by enterocytes.

What happens to chylomicrons after they enter the bloodstream?

Chylomicrons gain additional lipoproteins and are acted upon by lipoprotein lipase, which splits off fatty acids from triglycerides.

What is the role of serum albumin in lipid transport?

Serum albumin is responsible for transporting free fatty acids released from triglycerides.

What occurs to chylomicrons as they are depleted of triglycerides?

Their density increases and size decreases, eventually forming remnant fragments that are taken up by liver cells.

What is VLDL and how is it formed?

VLDL, or very-low-density lipoprotein, is formed from the remnants of chylomicrons in the liver, carrying endogenous lipids.

How does LDL deliver cholesterol to tissues?

LDL particles, composed mainly of cholesterol esters, deliver cholesterol to various tissues via receptor-mediated endocytosis.

What is reverse cholesterol transport?

Reverse cholesterol transport is the process by which HDL carries cholesterol away from peripheral tissues to the liver for disposal.

What is the significance of HDL's structure?

HDL particles are small and disc-shaped, carrying phospholipids and apolipoproteins, which help in picking up unesterified cholesterol.

What enzyme esterifies cholesterol in HDL?

Lecithin-cholesterol acyltransferase (LCAT) esterifies cholesterol in HDL.

How are triglycerides stored in adipocytes?

Triglycerides are stored in adipocytes as visible droplets, with a nonpolar core and a surface layer of phospholipids.

Why are fatty acids used for energy storage?

Fatty acids are highly reduced, providing more energy upon oxidation compared to sugars, and they pack closely together, promoting efficient storage.

What happens to excess cholesterol in the body?

Excess cholesterol can be cytotoxic, disrupting cell membranes, so it must be transported away from tissues.

What are the two main sources of fatty acids in adipocytes?

Fatty acids can enter adipocytes from circulation or be synthesized from glucose.

What metabolic pathway is involved in fatty acid synthesis from glucose?

Glucose is broken down to DHAP and pyruvate, which is converted to acetyl-CoA, entering the fatty acid biosynthetic pathway.

How does cholesterol interact with lipoprotein particles?

Cholesterol can be exchanged between lipoprotein particles and cell membranes, especially in blood vessels.

What is the consequence of high cholesterol levels in membranes?

High levels of cholesterol can disrupt cell membranes, necessitating careful regulation of cholesterol levels in the bloodstream.

What is the role of cholesterol esters in the body?

Cholesterol esters are more hydrophobic than cholesterol and do not readily penetrate membranes, aiding in cholesterol transport.

What is the role of cholesteryl esters in lipoprotein particles?

Cholesteryl esters are not readily exchanged into cell membranes; they are taken up by cells when the lipoprotein particle is endocytosed.

What happens to lipoprotein particles after endocytosis?

They form a vesicle that fuses with lysosomes, where hydrolytic enzymes break down cholesterol esters to release cholesterol and fatty acids.

How does the liver regulate cholesterol levels?

The liver is the major site of cholesterol biosynthesis and regulates lipoprotein particles through uptake of LDL and release of VLDL.

What is the function of acyl-CoA:cholesterol acyltransferase (ACAT)?

ACAT esterifies incoming free cholesterol, storing cholesteryl esters as droplets in liver cells.

What fatty acids are typically attached to cholesteryl esters in LDL particles?

Polyunsaturated fatty acids, such as linoleate, are typically attached and are replaced with mono-unsaturated fatty acids upon uptake.

What is lipolysis?

Lipolysis is the breakdown of triglycerides into free fatty acids and glycerol, initiated by hormonal signals.

Which hormones stimulate lipolysis?

Epinephrine, norepinephrine, glucagon, and adrenocorticotropic hormone (ACTH) stimulate lipolysis.

How does insulin affect lipolysis?

Insulin inhibits lipolysis by binding to a receptor-tyrosine kinase, which leads to the deactivation of hormone-sensitive lipase.

What is the process of fatty acid oxidation called?

The process is called β-oxidation, which occurs in the mitochondrial matrix.

What is required for fatty acids to cross the inner mitochondrial membrane?

Fatty acids or their CoA esters require a transport mechanism involving carnitine and specific transferases.

What is the significance of acetyl-CoA in lipid metabolism?

Acetyl-CoA generated from carbohydrate breakdown can be used for lipid biosynthesis.

What is the role of lysosomes in lipid metabolism?

Lysosomes contain enzymes that digest lipoproteins, releasing fatty acids and cholesterol for cellular use.

What is the fate of lipoprotein receptors after endocytosis?

Lipoprotein receptors are recycled back to the plasma membrane for reuse.

What is the initial event in the breakdown of triglycerides?

Lipolysis, which is the hydrolysis of triglycerides into free fatty acids and glycerol.

What is the role of protein kinases in lipolysis?

Protein kinases are activated by cAMP and phosphorylate hormone-sensitive lipase, activating it for lipolysis.

What is the relationship between fatty acid metabolism and carbohydrate metabolism?

Fatty acid metabolism is closely tied to carbohydrate metabolism, with acetyl-CoA being a key intermediate.

What are the main types of lipases produced by the body?

Some lipases are secreted into the gastrointestinal tract, others act on lipoprotein particles, and some act on internal fat stores.

What is the process by which triglycerides are hydrolyzed?

Triglycerides are hydrolyzed by hormone-sensitive lipase, releasing free fatty acids and glycerol.

What is the role of G-protein-coupled receptors in lipolysis?

They bind stimulatory hormones, leading to increased cAMP levels and activation of lipase.

What is the significance of the Golgi complex in lipid metabolism?

The Golgi complex is involved in the synthesis and processing of new receptors for lipoproteins.

What happens to triglycerides when energy is needed by the body?

Hormones stimulate the mobilization of triglycerides, leading to their hydrolysis and release of free fatty acids.

What is the main function of adipocytes in lipid metabolism?

Adipocytes store triglycerides and release free fatty acids when energy is required.

What is the role of cAMP in the regulation of lipase activity?

cAMP acts as a second messenger that activates protein kinases, which phosphorylate and activate lipase.

What is the outcome of the breakdown of triglycerides?

The breakdown releases one molecule of glycerol and three fatty acids per triglyceride molecule.

What hormones are involved in initiating lipolysis?

Glucagon and Epinephrine

What is the role of cAMP in lipolysis?

cAMP acts as a second messenger that initiates a cascade of protein phosphorylations leading to the activation of lipase.

What is the function of hormone-sensitive lipase?

It hydrolyzes triglycerides into free fatty acids and glycerol.

What happens to glycerol after it is released from adipose tissue?

Glycerol enters the glycolytic pathway as DHAP after phosphorylation.

How are free fatty acids transported in the bloodstream?

Free fatty acids are transported bound to serum albumin.

What is the role of carnitine in fatty acid metabolism?

Carnitine facilitates the transport of acyl groups across the mitochondrial membrane.

What enzyme catalyzes the formation of O-acylcarnitine?

Carnitine palmitoyl transferase 1 (CPT1)

What is the effect of malonyl-CoA on CPT1 activity?

Malonyl-CoA inhibits CPT1, preventing the entry of fatty acids into the mitochondria for oxidation.

What occurs during the first step of β-oxidation?

A fatty acid is oxidized, generating FADH2 and forming a trans-2-enoyl-CoA intermediate.

What is the end product of one round of β-oxidation?

Each round of β-oxidation produces one molecule of acetyl-CoA, FADH2, and NADH.

What distinguishes the oxidation of fatty acids with an odd number of carbons?

They yield one molecule of propionyl-CoA along with acetyl-CoA at the final round of β-oxidation.

What is the fate of fatty acids after they are released from adipose tissue?

Fatty acids enter a special oxidative pathway (β-oxidation) to generate ATP.

What is the role of CPT2 in fatty acid metabolism?

CPT2 reattaches the acyl group to CoA after O-acylcarnitine is transported into the mitochondrial matrix.

What happens to the acyl-CoA generated in the mitochondrial matrix?

It becomes a substrate for the β-oxidation process.

Describe the process of thiolysis in β-oxidation.

Thiolysis involves the cleavage of the acyl-CoA to release acetyl-CoA and shorten the fatty acid chain by two carbons.

What is the significance of the trans geometry in the intermediate of β-oxidation?

The trans geometry is characteristic of the double bond formed during the oxidation step and does not accumulate in significant amounts.

How does the cell regulate the balance between fatty acid oxidation and biosynthesis?

The levels of malonyl-CoA provide an indirect measure of the cell's readiness for fatty acid biosynthesis versus oxidation.

What is the role of serum albumin in fatty acid transport?

Serum albumin binds to free fatty acids, enhancing their solubility and transport in the bloodstream.

What is the first step in the β-oxidation reaction sequence?

Oxidation of the fatty acid to form a trans-2-enoyl-CoA.

What happens during the hydration step of β-oxidation?

Water is added to the trans-2-enoyl-CoA to form 3-hydroxyacyl-CoA.

What is produced during the oxidation step of β-oxidation?

3-hydroxyacyl-CoA is oxidized to form 3-ketoacyl-CoA.

What is the final product of the thiolysis step in β-oxidation?

The final product is a shortened acyl-CoA and acetyl-CoA.

What is propionyl-CoA converted to for further metabolism?

Succinyl-CoA

What special cofactor is required for the conversion of propionyl-CoA?

A cofactor derived from vitamin B12 (cobalamin)

What enzyme catalyzes the carboxylation of propionyl-CoA?

Propionyl-CoA Carboxylase

What is the role of AdoCbl in metabolism?

It is involved in the conversion of L-methylmalonyl-CoA to succinyl-CoA.

What are the products generated from the metabolism of succinyl-CoA in the TCA cycle?

One NADH, one GTP, and one FADH2.

What is the significance of intrinsic factor in vitamin B12 absorption?

It binds cobalamin and facilitates its transport across the ileum.

What condition arises from impaired uptake of vitamin B12?

Pernicious anemia

What are some symptoms of pernicious anemia?

Megaloblastic anemia, damage to myelinated nerve cells, and peripheral neuropathy.

What dietary sources are rich in vitamin B12?

Meat, eggs, and dairy foods.

What is the role of methylcobalamin in metabolism?

It is used as a cofactor in the conversion of homocysteine to methionine.

What is a consequence of vitamin B12 deficiency on DNA synthesis?

Impaired DNA synthesis affects rapidly dividing tissues, particularly red blood cells.

What is the process of a-oxidation in fatty acid metabolism?

It shortens the fatty acid chain by one carbon at a time, releasing CO2.