Chapter 11: Lipid And Amino Acid Metabolism

Question 1

Dietary fat

Answer 1

Composed of triacylglycerols, cholesterol, cholesteryl esters, phospholipids, and free fatty acids

Question 2

Emulsification

Answer 2

Mixing of two normally immiscible liquids (fat and water); formation of an emulsion increases the surface area of the lipid, which permits greater enzymatic interaction and processing; aided by bile which contains bile salts, pigments, and cholesterol; bile is secreted by the liver and stored in the gallbladder; the pancreas secretes pancreatic lipase, colipase, and cholesterol esterase into the small intestine, forming free fatty acids, cholesterol, and 2-monoacylglycerol

Question 3

Micelle

Answer 3

Cluster of amphipathic lipids that are soluble in the aqueous environment of the intestinal lumen; water-soluble spheres with lipid soluble interiors; vital in digestion, transport, and absorption of lipid-soluble substances starting from the duodenum all the way to the end of the ileum

Question 4

What happens at the end of the ileum?

Answer 4

Bile salts are actively reabsorbed and recycled; any fat remaining in the intestine will pass into the colon and ultimately end up in the stool

Question 5

Absorption

Answer 5

Micelles diffuse to brush border of the intestinal mucosal cells where they are absorbed; the digested lipids pass through the brush border where they are absorbed into the mucosa and re-esterified to form triacylglycerols and cholesteryl esters and packaged along with certain apoproteins, fat-soluble vitamins and other lipids into chylomicrons

Question 6

Chylomicrons

Answer 6

Leave the intestine via lacteals, the vessels of the lymphatic system and re-enter the bloodstream via the thoracic duct, a long lympathic vessel that empties into the left subclavian vein at the base of the neck; more water-soluble short-chain fatty acids can be absorbed by simple diffusion directly into the bloodstream

Question 7

Hormone-sensitive lipase (HSL)

Answer 7

Hydrolyzes triacylglycerols, yielding fatty acids and glycerol; activated by a decrease in insulin or release of epinephrine/cortisol; effective within adipose cells

Question 8

Lipoprotein lipase (LPL)

Answer 8

Necessary for the metabolism of chylomicrons and VLDL; enzyme that releases free fatty acids from triacylglycerols in these lipoproteins

Question 9

How are FFA carried in the blood?

Answer 9

Bound to albumin, a carrier protein

Question 10

How are triacylglycerol and cholesterol transported in the blood?

Answer 10

As lipoproteins: aggregates of apolipoproteins and lipids

Question 11

Chylomicrons

Answer 11

Least dense lipoprotein; highest fat-to-protein ratio; transports dietary triacylglycerols and cholesterol from intestine to tissues; highly soluble in both lymphatic fluid and blood; assembly of chylomicrons occurs in the intestinal lining and results in a nascent chylomicron that contains lipids and apolipoproteins

Question 12

Very low density lipoprotein (VLDL)

Answer 12

Metabolism is similar to that of chylomicrons; however, VLDL is produced and assembled in liver cells; the main function is to transport triacylglycerol from the liver to tissues; also contains fatty acids that are synthesized from excess glucose or retrieved from chylomicron remnants

Question 13

IDL

Answer 13

Intermediate density lipoprotein or VLDL remnant; some IDL is resabsorbed by the liver by apolipoproteins on its exterior and some is further processed in the bloodstream; some IDL picks up cholesteryl esters from HDL to become LDL; IDL this exists as a transition particle between triacylglycerol transport (associated with chylomicrons and VLDL) and cholesterol transport (associated with LDL and HDL)

Question 14

Low density lipoprotein (LDL)

Answer 14

Primarily a cholesterol particle; majority of the cholesterol measured in blood is associated with LDL; the normal role of LDL is to deliver cholesterol to tissues for biosynthesis (and cell membranes); bile acids and salts are made from cholesterol in the liver and many other tissues require cholesterol for steroid hormone synthesis (steroidogenesis)

Question 15

High density lipoprotein (HDL)

Answer 15

Synthesized in the liver and intestines and released as dense, protein-rich particles into the blood; HDL contains apolipoproteins used for cholesterol recovery (cleaning up of cholesterol from blood vessels for excretion); HDL also delivers some cholesterol to steroidogenic tissues and transfers necessary apolipoproteins to some of the other lipoproteins

Question 16

Apolipoproteins

Answer 16

Apoproteins from the protein component of the lipoproteins; receptor molecules and are involved in signaling

Question 17

ApoA-1

Answer 17

Activates LCAT, an enzyme that catalyzes cholesterol esterification

Question 18

ApoB-48

Answer 18

Mediates chylomicron secretion

Question 19

ApoB-100

Answer 19

Permits uptake of LDL by the liver

Question 20

ApoC-II

Answer 20

Activates lipoprotein lipase

Question 21

ApoE

Answer 21

Permits uptake of chylomicron remnants and VLDL by the liver

Question 22

Cholesterol

Answer 22

Ubiquitous component of all cells in the human body and plays a major role in the synthesis of cell membranes, steroid hormones, bile acids, and vitamin D

Question 23

Sources of cholesterol

Answer 23

Most cells derive their cholesterol from LDL or HDL, but some cholesterol many be synthesized de novo

Question 24

Where does de novo cholesterol synthesis occur?

Answer 24

Liver; driven by acetyl-CoA and ATP

Question 25

Citrate shuttle

Answer 25

Carries mitochondrial acetyl-CoA into the cytoplasm, where synthesis occurs; NADPH (from the pentose phosphate pathway) supplies reducing equivalents; synthesis of mevalonic acid in the smooth ER is the rate-limiting step in cholesterol biosynthesis and is catalyzed by 3-hydroxy-3-methylglutaryl (HMG) CoA reductase

Question 26

How is cholesterol synthesis regulated?

Answer 26

1) Increased levels of cholesterol can inhibit further synthesis by a feedback inhibition mechanism
2) Insulin promotes cholesterol synthesis
3) Regulation of HMG-CoA reductase gene expression in the cell

Question 27

Lecithin-cholesterol acyltransferase (LCAT)

Answer 27

Enzyme found in the bloodstream that is activated by HDL apoproteins ; adds a fatty acid to cholesterol, which produces soluble cholesteryl esters such as those in HDL

Question 28

How does IDL become LDL?

Answer 28

Acquires cholesteryl esters from HDL

Question 29

Cholesteryl ester transfer protein (CETP)

Answer 29

Facilitates the transfer process of chosteryl ester from HDL to IDL to form LDL

Question 30

Nontemplate synthesis

Answer 30

Do not rely directly on the coding of a nucleic acid, unlike protein and nucleic acid synthesis; excess carbohydrate and protein acquired from the diet can be converted to fatty acids and stored as energy reserves in the form of triacylglycerol

Question 31

Palmitic acid

Answer 31

Palmitate - primary end product of fatty acid synthesis

Question 32

Acetyl-CoA shutting

Answer 32

Citrate can diffuse across the mitochondrial membrane; in the cytosol, citrate synthase splites citrate back into acetyl-CoA and oxaloacetate; the oxaloacetate can then return to the mitochondrion to continue moving acetyl-CoA

Question 33

Acetyl-CoA Carboxylase

Answer 33

Acetyl-CoA is activated in the cytoplasm for incorporation into fatty acids by acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid biosynthesis; acetyl-CoA carboxylase requires biotin and ATP to function; adds CO2 to acetyl-CoA to form malonyl-CoA; enzyme is activated by insulin and citrate

Question 34

Fatty acid synthase

Answer 34

AKA palmitate synthase because palmitate is the only fatty acid that humans can synthesize de novo; large multienzyme complex found in the cytosol that is rapidly induced in the liver following a meal high in carbohydrates because of elevated insulin levels; enzyme complex contains an acyl carrier protein (ACP) that requires pantothenic fatty acid; involves forming a bond with malonyl-CoA and the growing chain, reducingof a carboxyl group, dehydration, and reduction of a double bond with NADPH

Question 35

Triacylglycerol synthesis

Answer 35

Occurs primarily in the liver and somewhat in the adipose tissue, with a small contribution directly from the diet; in the liver, TAGs are packaged and sent to adipose tissue via VLDL; only a small amount remains in the liver

Question 36

Where does β-oxidation occur?

Answer 36

Mostly in the mitochondira; however, some peroxisomal β-oxidation also occurs

Question 37

Α-oxidation

Answer 37

Branched fatty acids

Question 38

Omega oxidation

Answer 38

In the endoplasmic reticulum produces dicarboxylic acids

Question 39

Fatty-acyl-CoA synthetase

Answer 39

Activate fatty acids through attachment to CoA, producing fatty acyl-CoA or acyl-CoA

Question 40

How do fatty acids enter the mitochondria?

Answer 40

Short-chain fatty acids (2-4 C) and medium chain fatty acids (6 to 12 C) diffuse freely into the mitochondria; long-chain fatty acids (14 to 20 C) require transport via a carnitine shuttle

Question 41

Carnitine acetyltransferase I

Answer 41

Rate-limiting enzyme of fatty acid oxidation; very long fatty acids (>20C) are oxidized elsewhere in the cell

Question 42

Β-oxidation

Answer 42

Four step process; oxidation to form double bond, releasing FADH2; hydration; oxidation of β-C OH group with NAD+, forming NADH; splitting of the β-ketoacid into a shorter acyl-CoA and acetyl-CoA

Question 43

Propionyl-CoA carboxylase

Answer 43

Requires biotin; yield propionyl-CoA which is converted to methylmalonyl-CoA by propionyl-CoA carboxylase —> converted to succinyl-CoA by methlmalonyl-CoA mutase which requires cobalamin (vitamin B12); succinyl-CoA is a CAC intermediate (exception to the rule that FFA cannot form glucose)

Question 44

Enzymes for oxidation of unsaturated FA

Answer 44

Enoyl-CoA isomerase - rearranges cis double bonds at the 3,4 position to trans double bonds at the 2,3 position once enough acetyl-CoA has been liberated to isolate th double bond within the first three C
2,4-dienoyl-CoA reductase - converts 2 conjugated double bonds to just one double bond at the 3,4 position (for polyunsaturated fatty acids)

Question 45

Where are fatty acids synthesized? Where are they modified?

Answer 45

In the cytoplasm; in the SER

Question 46

In the fasting state, what does the liver convert excess acetyl-CoA into?

Answer 46

Acetoacetate and β-hydroxybutyrate (used by cardiac and skeletal muscle, renal cortex, and the brain (if ketone bodies are high))

Question 47

Ketogenesis

Answer 47

Occurs in the mitochondria of liver cells when excess acetyl-CoA accumulates in the fasting state; HMG-CoA synthase forms HMG-CoA and HMG-CoA lyase breaks down HMG-CoA into acetoacetate which can be reduced to β-hydroxybutyrate (acetone is a minor side product)

Question 48

Ketolysis

Answer 48

Occurs in the mitochondria; acetoacetate from the blood is activated by succinyl-CoA acetoacetyl-CoA transferase (thiophorase) that only exists in tissues outside the liver; 3-hydroxybutyrate is oxidized to acetoacetate; acetoacetate —> acetoacetyl-CoA —> acetyl-CoA (enters the CAC)

Question 49

What happens in the brain during prolonged fasting (over one week of fasting)

Answer 49

Brain begins to derive up to 2/3 of its energy from ketone bodies; results in the accumulation of acetyl-CoA which inhibits the PDH complex, reducing glycolysis and glucose uptake to preserve muscle

Question 50

Review protein digestion and absorption

Answer 50

OK

Question 51

Where is body protein primarily catabolized?

Answer 51

Liver and muscle

Question 52

How do amino acids released from proteins lose their amino groups?

Answer 52

Transamination or deamination; the amino group (as well as basic aide chains) enter the urea cycle

Question 53

Glucogenic amino acids

Answer 53

Can be converted into glucose via gluconeogenesis (all except leucine and lysine)

Question 54

Ketogenic amino acids

Answer 54

Can be converted into acetyl-CoA and ketone bodies; including leucine, lysine, isoleucine, threonine, tryptophan, phenylalanine, and tyrosine