Lipid metabolism

Question 1

What are lipids?

Answer 1

Lipids are a chemically diverse group of compounds that are insoluble in water and have various biological functions.

Question 2

What are the principal functions of lipids?

Answer 2

Lipids serve as a principal source of stored energy, major structural elements of biological membranes, and play important roles in metabolism, signaling events, and as precursors of steroid hormones.

Question 3

What is the structure of storage lipids?

Answer 3

Storage lipids, such as triglycerides, consist of 1 glycerol molecule and 3 fatty acid molecules.

Question 4

What are membrane lipids?

Answer 4

Membrane lipids are polar lipids that contribute to the structure of biological membranes.

Question 5

What is the structure of phospholipids?

Answer 5

Phospholipids, a type of membrane lipid, consist of 1 glycerol molecule, 2 fatty acid molecules, an alcohol, and a phosphate group.

Question 6

What are sphingolipids?

Answer 6

Sphingolipids are a type of membrane lipid composed of sphingosine, a fatty acid, a phosphate group, and either choline or a mono- or oligosaccharide.

Question 7

What are glycolipids?

Answer 7

Glycolipids are a type of membrane lipid that can be sphingolipids (composed of sphingosine, a fatty acid, and a mono- or oligosaccharide) or galactolipids/sulfolipids (composed of glycerol, 2 fatty acids, and a mono- or disaccharide and a sulfate group).

Question 8

What is the relationship between lipids and other energy sources?

Answer 8

Lipids, such as triglycerides, serve as an energy source alongside carbohydrates and proteins in the body.

Question 9

What is the function of cholesterol?

Answer 9

Cholesterol is a type of lipid that plays a major role in maintaining the integrity and fluidity of cell membranes and serves as a precursor for the synthesis of steroid hormones.

Question 10

What is the primary role of triglycerides or fats?

Answer 10

Triglycerides constitute approximately 90% of dietary lipids and serve as the major form of metabolic energy storage in humans.

Question 11

How do saturated fatty acids differ from unsaturated fatty acids?

Answer 11

Saturated fatty acids have no double bonds between carbon atoms, while unsaturated fatty acids have at least one double bond.

Question 12

What is the significance of the degree of unsaturation in fatty acids?

Answer 12

The degree of unsaturation affects the melting point and fluidity of fatty acids. Fatty acids with more double bonds (polyunsaturated fatty acids) have lower melting points and increased fluidity.

Question 13

What are the two major metabolic pathways of triglycerides?

Answer 13

Triglycerides can be metabolized through oxidation in the mitochondria to release energy in the form of ATP or synthesized from malonyl-CoA for storage.

Question 14

What is beta-oxidation of triglycerides?

Answer 14

Beta-oxidation is the process by which triglycerides are broken down in the mitochondria, resulting in the release of energy in the form of ATP.

Question 15

What is the role of cholesterol in cellular function?

Answer 15

Cholesterol plays a vital role in maintaining the integrity and fluidity of cell membranes and serves as a precursor for the synthesis of steroid hormones.

Question 16

How is cholesterol synthesized in the body?

Answer 16

Cholesterol synthesis occurs mainly in the liver. It involves a series of enzymatic reactions, starting from acetyl-CoA and proceeding through multiple steps to produce cholesterol.

Question 17

What is the metabolism of cholesterol?

Answer 17

Cholesterol metabolism involves the uptake of cholesterol from dietary sources, synthesis in the body, conversion to bile acids in the liver, and elimination through feces.

Question 18

What is the role of b-oxidation in triglyceride metabolism?

Answer 18

Beta-oxidation is the process where fatty acids are broken down into acetyl-CoA units, which can enter the citric acid cycle to produce ATP. This process is essential for the oxidation of fatty acids stored in triglycerides.

Question 19

What are the three stages involved in the complete oxidation of fatty acids?

Answer 19

The three stages are: oxidation of long-chain fatty acids to acetyl-CoA (β-oxidation), oxidation of acetyl-CoA to CO2 in the citric acid cycle, and transfer of electrons from reduced electron carriers to the mitochondrial respiratory chain.

Question 20

What is the process of β-oxidation?

Answer 20

β-oxidation is an oxidative process that occurs in the mitochondria and involves the successive removal of 2-carbon fragments as acetyl-CoA from fatty acids.

Question 21

How are fatty acids activated for β-oxidation?

Answer 21

Fatty acids are activated by attachment to Coenzyme A (CoA) in the cytosol.

Question 22

What is the rate-limiting step of β-oxidation?

Answer 22

The transfer of acyl-groups across the mitochondrial membrane is the rate-limiting step of β-oxidation.

Question 23

What happens during each cycle of β-oxidation?

Answer 23

During each cycle, the fatty acid chain is shortened by a 2-carbon unit, resulting in the formation of one acetyl-CoA, one FADH2, and one NADH. The process is catalyzed by a group of dehydrogenase isozymes.

Question 24

What can mutations in the dehydrogenase isozymes of β-oxidation cause?

Answer 24

Mutations in these dehydrogenase isozymes can cause Sudden Infant Death Syndrome (SIDS).

Question 25

What is the consequence of mutations in the Acyl-CoA dehydrogenase enzyme complex?

Answer 25

Mutations in this enzyme complex can inhibit the first stage of β-oxidation, leading to Medium-chain acyl-CoA dehydrogenase deficiency (MCADD).

Question 26

What is MCADD?

Answer 26

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder caused by mutations in the ACADM gene, resulting in impaired fatty acid oxidation. Clinical symptoms may include lethargy, hypoglycemia, seizures, and vomiting.

Question 27

How is MCADD typically diagnosed?

Answer 27

MCADD is often diagnosed through newborn blood spot testing.

Question 28

Where does fatty acid synthesis primarily occur?

Answer 28

Fatty acid synthesis mainly occurs in the liver and adipocytes.

Question 29

How are long carbon chain molecules built during fatty acid synthesis?

Answer 29

Long carbon chain molecules are built up from 2-carbon units derived from acetyl-CoA and a 3-carbon malonyl-CoA intermediate.

Question 30

Where does fatty acid synthesis occur?

Answer 30

Fatty acid synthesis takes place in the cytosol of cells.

Question 31

How does acetyl-CoA get out of the mitochondria for fatty acid synthesis?

Answer 31

Acetyl-CoA is converted to citrate for transport out of the mitochondria, then converted back to acetyl-CoA in the cytosol for use in fatty acid synthesis. The oxaloacetate produced in this process is then converted back to pyruvate for transport back into the mitochondria for use in ATP synthesis.

Question 32

What is the first committed step of fatty acid biosynthesis?

Answer 32

The conversion of citrate to acetyl-CoA and CO2 by the enzyme acetyl-CoA carboxylase is the first committed step of fatty acid biosynthesis.

Question 33

What is the role of malonyl-CoA in fatty acid synthesis?

Answer 33

Malonyl-CoA, along with acetyl-CoA, binds to fatty acid synthase and serves as the precursor for adding further C2 units in the repeating series of condensation reactions during fatty acid synthesis.

Question 34

How many cycles of condensation reactions are needed to yield palmitate?

Answer 34

The cycle of condensation reactions repeats seven times, adding 2 carbon units each time, to yield a 16-carbon palmitate.

Question 35

What is the rate-limiting step of β-oxidation?

Answer 35

The transfer of acetyl-CoA into the mitochondria is the rate-limiting step of β-oxidation.

Question 36

What is the rate-limiting step of fatty acid synthesis?

Answer 36

The formation of malonyl-CoA from acetyl-CoA, catalyzed by acetyl-CoA carboxylase, is the rate-limiting step of fatty acid synthesis.

Question 37

How is the control of fatty acid synthesis regulated?

Answer 37

The enzyme acetyl-CoA carboxylase, which catalyzes the formation of malonyl-CoA, is subject to phosphorylation under the control of glucagon hormone.

Question 38

What is the role of HMG-CoA reductase in cholesterol synthesis?

Answer 38

HMG-CoA reductase is an enzyme involved in the synthesis of cholesterol. It catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonate, a crucial step in cholesterol biosynthesis.

Question 39

What is the importance of cholesterol in the body?

Answer 39

Cholesterol is an essential molecule in many animals, including humans. It is not required in the diet as all cells can synthesize it. Cholesterol plays a vital role in various physiological processes, but its deposition in arteries is associated with heart disease and stroke.

Question 40

How is cholesterol eliminated from the body?

Answer 40

Cholesterol is eliminated as bile acids, which are produced from cholesterol by the liver and excreted into the gall bladder. Bile acids aid in the digestion and absorption of dietary fats.

Question 41

What are cholesterol esters and how are they formed?

Answer 41

Cholesterol esters are the storage form of cholesterol found in most tissues. The formation of cholesterol esters is catalyzed by cholesterol acyltransferases, such as Acyl-CoA Cholesterol Acyltransferase (ACAT).

Question 42

What are bile acids and what is their function?

Answer 42

Bile acids are relatively hydrophilic cholesterol derivatives that act as emulsifiers. They are produced from cholesterol by the liver and are excreted into the gall bladder for release into the small intestine. Bile acids help in the emulsification of fats, increasing their surface area for enzymatic digestion.

Question 43

What happens to most bile acids after their function in digestion?

Answer 43

Most bile acids are reabsorbed in the gut and returned to the liver for recycling. This enterohepatic circulation allows for efficient reuse of bile acids.

Question 44

Where is the major site of cholesterol synthesis in the body?

Answer 44

The major site of cholesterol synthesis is the liver, although lesser amounts are also synthesized in the intestine and adrenal cortex.

Question 45

What is the rate-determining step in cholesterol biosynthesis?

Answer 45

The conversion of HMG-CoA to mevalonate, catalyzed by HMG-CoA reductase, is the rate-determining step in cholesterol biosynthesis. Both cholesterol and mevalonate act as feedback inhibitors of this enzyme.

Question 46

What is the significance of HMG-CoA reductase as a target for statin drugs?

Answer 46

HMG-CoA reductase is the target site for statin drugs, which are commonly used to lower cholesterol levels. By inhibiting this enzyme, statins reduce the production of cholesterol in the body.

Question 47

How is the activity of HMG-CoA reductase regulated?

Answer 47

The activity of HMG-CoA reductase, the enzyme involved in cholesterol synthesis, is regulated by insulin and glucagon hormones. Insulin activates HMG-CoA reductase, while glucagon inhibits its activity.

Question 48

What are the four stages of cholesterol biosynthesis?

Answer 48

Stage 1: Synthesis of mevalonate from acetate.
Stage 2: Conversion of mevalonate to two activated isoprenes.
Stage 3: Condensation of six isoprene units to form squalene.
Stage 4: Cyclization of squalene to form the four-ring steroid nucleus.

Question 49

How is mevalonate synthesized from acetate?

Answer 49

Mevalonate is synthesized from acetate through a series of enzymatic reactions, including the condensation of three acetate molecules and the subsequent conversion to mevalonate.

Question 50

What are the activated isoprenes formed from mevalonate?

Answer 50

Mevalonate is converted into two activated isoprenes: isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). These isoprenes serve as building blocks for the synthesis of larger isoprenoid compounds.

Question 51

How is squalene formed in cholesterol biosynthesis?

Answer 51

Six molecules of IPP and DMAPP condense to form farnesyl pyrophosphate (FPP), which is further condensed to form squalene, a key intermediate in cholesterol biosynthesis.

Question 52

What is the final step in cholesterol biosynthesis?

Answer 52

The cyclization of squalene leads to the formation of the four-ring steroid nucleus, which serves as the backbone of cholesterol and other steroid molecules.

Question 53

Why do we transport lipids around the body?

Answer 53

Lipids are transported around the body to bring dietary lipids to cells for energy production or storage, move lipids from storage in adipose tissue for energy production, provide lipids from the diet to cells for synthesizing cell membranes, and carry cholesterol from peripheral tissues to the liver for excretion.

Question 54

How are lipids transported in the blood?

Answer 54

Short-chain fatty acids are transported bound to blood proteins like albumin. For the bulk transport of neutral lipids, which are insoluble in water, special carrier proteins called lipoproteins are used.

Question 55

What are lipoproteins?

Answer 55

Lipoproteins are composed of hydrophilic, hydrophobic, and amphipathic molecules and serve as carriers for transporting lipids in the blood. They have specific functions determined by their point of synthesis, lipid composition, and apolipoprotein content.

Question 56

What are the major classes of plasma lipoproteins?

Answer 56

Chylomicron: Largest and least dense lipoprotein, involved in exogenous lipid transport from intestinal tissues. Key lipoproteins: ApoE, ApoC-II. Contains high levels of triglycerides (TG) and low levels of cholesterol and cholesterol esters.
VLDL (Very Low-Density Lipoprotein): Involved in endogenous lipid transport, originating in the liver and transporting lipids to muscle and adipose tissue. Key lipoproteins: ApoE, ApoC-II. Contains high levels of triglycerides (TG) and moderate levels of cholesterol and cholesterol esters.
LDL (Low-Density Lipoprotein): Involved in endogenous transport, carrying cholesterol to muscle, adrenal glands, and adipose tissue. Key lipoprotein: ApoB-100. Contains moderate levels of triglycerides (TG), cholesterol, and high levels of cholesterol esters.
HDL (High-Density Lipoprotein): Involved in reverse transport, originating in the liver and small intestine, and returning cholesterol to the liver. Key lipoproteins: ApoE. Contains low levels of triglycerides (TG), cholesterol, and cholesterol esters.

Question 57

What are the functions of chylomicrons, VLDL, LDL, and HDL?

Answer 57

Chylomicrons are involved in the transport of dietary fats, VLDL transports endogenous lipids, LDL carries cholesterol to specific tissues, and HDL is involved in reverse transport, returning cholesterol to the liver.

Question 58

How are dietary triacylglycerols (TGs) digested and absorbed?

Answer 58

Dietary TGs undergo two major steps in digestion. First, they are emulsified by bile acids, which are detergent-like molecules. Then, they are hydrolyzed by the enzyme pancreatic triacylglycerol lipase. The products of lipid digestion are a mixture of fatty acids and mono- and diacylglycerols, which can be absorbed by the intestinal mucosa. Bile acids are also essential for this absorption process.

Question 59

What is the exogenous pathway of lipid transport?

Answer 59

The exogenous pathway involves the transport of lipids from the intestine as dietary fat. The lipids are packaged as chylomicrons and travel to tissues. ApoC-II apolipoprotein present on chylomicrons stimulates tissue-bound lipoprotein lipase enzymes, which release triacylglycerides from chylomicrons. The remnants of chylomicrons are endocytosed by the liver, which recognizes them by their ApoE apolipoprotein.

Question 60

What is the role of apolipoproteins in lipid transport?

Answer 60

Apolipoproteins are specific carrier proteins that combine with lipids to form different classes of plasma lipoproteins. They have specific functions, such as targeting lipoproteins to tissues or activating enzymes that act on lipoproteins.

Question 61

How does reverse cholesterol transport occur?

Answer 61

Reverse cholesterol transport is the process by which excess cholesterol is transported from peripheral tissues back to the liver. HDL (High-Density Lipoprotein) plays a crucial role in reverse cholesterol transport. HDL, which originates from the liver and small intestine, removes cholesterol from tissues and transports it back to the liver for excretion. ApoE is a key lipoprotein involved in this process.

Question 62

What are the roles of LDL and HDL in lipid transport?

Answer 62

LDL (Low-Density Lipoprotein) carries cholesterol to specific tissues, while HDL is involved in reverse cholesterol transport, returning cholesterol to the liver for excretion. LDL contains ApoB-100, while HDL contains ApoE as a key lipoprotein.

Question 63

What is the endogenous pathway of lipid transport?

Answer 63

The endogenous pathway involves the transport of lipids from the liver to adipose/muscle tissues as VLDL (Very Low-Density Lipoprotein) lipoproteins. ApoC-II activates tissue-bound lipoprotein lipases, which release fatty acids. Triacylglyceride-depleted remnants of VLDLs become IDL (Intermediate Density Lipoproteins), and further loss of triacylglycerides leads to the formation of LDL (Low-Density Lipoproteins). LDL, which is cholesterol/cholesterol ester-rich, is taken up by endocytosis within the extrahepatic tissues through binding of ApoB-100 to LDL receptors on the cell surface of the liver and extrahepatic tissues.

Question 64

How does lipid reverse transport occur?

Answer 64

Endogenous cholesterol and cholesterol esters from extrahepatic tissues are transported back to the liver via HDL (High-Density Lipoproteins). HDL does not enter the liver through endocytosis but binds to scavenger receptors (SR-B1) on the cell surface, facilitating the transfer of cholesterol into the cell.

Question 65

How is LDL (cholesterol) taken up by cells?

Answer 65

LDL uptake by cells is mediated by LDL receptors on the cell surface binding to ApoB-100. This allows the internalization of LDL particles into the cells.

Question 66

How is intracellular cholesterol regulated?

Answer 66

Cellular cholesterol levels are regulated by controlling LDL-cholesterol uptake and biosynthesis. In the short term, regulation is achieved by modifying the activity of HMG-CoA reductase, the enzyme involved in cholesterol biosynthesis. In the long term, regulation is achieved by modifying the numbers of molecules involved in maintaining cellular cholesterol levels, such as HMG-CoA reductase and LDL receptors. Under high cholesterol levels, protein degradation of HMG-CoA reductase and LDL receptors reduces their numbers. LDL receptors that have internalized LDL are separated from LDL and recycled back to the cell surface. Endosomes containing LDL fuse with lysosomes, where lytic enzymes degrade ApoB-100, releasing amino acids, fatty acids, cholesterol, and cholesterol esters.