LECTURE 25 - MIDTERM 3

Question 1

T or F, fat is the major energy storage form in most organisms

Answer 1

True; most of the fat is in the form of triaglycerols, also known as triglycerides

–

Question 2

T or F, Mammals are 5-20% fat and 90% is TG

Answer 2

True, this 90% is also known as neutral fat as they don’t have charged groups in their chemical structure

– Excess carbohydrates, that exceed the levels that can be stored as glycogen, are made into triacylglycerols and stored in fat cells for later use.

– Our bodies convert any calories not needed right away into triglycerides for energy storage. Fats are also important to cushion organs and regulate body temperature.

Question 3

Describe the storage of fat in the body.

Answer 3

– stored in adipocytes (fat cells)

– unlike glycogen storage, fat storage is not limited; in normal weight adults, cane be up to 15 kg or more

– fat is more highly reduced, so contains more energy and is less hydrated, so lighter in weight

– we would have to be 2x as large to store our fat supply as glycogen

Question 4

T or F, we need energy for muscle contraction, transport processes, synthesis of macromolecules

Answer 4

True

Question 5

Theoretically where can our energy requirement come from?

Answer 5

– they can come from carbs and protein, but most diets don’t provide enough to fuel glucose requirements

– most diets in developed countries are 10-15% protein, remainder carbohydrates and fat

– the highly reduced nature of TG yields more energy than glucose

– most energy from fat breakdown comes from oxidation of the fatty acid tails

Question 6

Where do TGs used for fuel come from ?

Answer 6

1. ) diet
2. ) biosynthesis (primarily liver)
3. ) storage in adipocytes

– when digesting, absorbing, and transporting lipids, animals must deal with the problem of their insolubility in aqueous environments

Question 7

T or F, triglycerides are too large to be absorbed so they have to be digested.

Answer 7

True

Question 8

What are Bile salts?

Answer 8

– bile salts are synthesized in liver and stored in gall bladder until being released in the duodenum (beginning of small intestine)

– they are derived from cholesterol. Main type is cholic acid, but there are others as well

– Bile salts facilitate emulsion due to their amphipathic nature and digestion by lipase

Question 9

How do bile salts function?

Answer 9

– They function as a detergent, associating with the hydrophobic fats and allowing them to interface with the aqueous environment.

– The main function of bile salts is to emulsify fats, which is possible due to their amphipathic properties, containing hydrophobic and hydrophilic elements.

– Bile salts break apart large fat globules and make them accessible to water soluble enzymes, such as pancreatic lipase.

Question 10

Where does lipase come in?

Answer 10

– Once we have exposed the surface area of the fat globules by bile salts from the liver, a specialized pancreatic enzyme known as lipase, catalyzes the breakdown of fats to fatty acids and glycerol.

– Specifically, lipase is also secreted into the duodenum from the pancreas. L

– ipase digests the triacylglycerols into monoacylglycerols and free fatty acids or diacylglycerols and free fatty acid.

– The products of this activity can then be absorbed down the concentration gradient via passive diffusion across the intestinal epithelium.

Question 11

What is the purpose of the breakdown of TGs?

Answer 11

– the break down of TGs is just to get them across the plasma membrane of the intestinal cells

Question 12

Why can’t lipids travel through blood?

Answer 12

– bc lipids are hydrophobic and that’s why triglycerides are packaged

– can have triglyceride and can also have a monoglyceride

Question 13

Where are TGs resynthesized?

Answer 13

– intestinal cells

Question 14

What are chylomicrons and what are their purpose?

Answer 14

– TGs can’t diffuse back across membrane and would be insoluble in blood

– so they are arranged with chylomicorns (a form of lipoprotein aggregate), which have a polar surface of protein and polar lipids

– cholesterol is esterified so that i can be put into the hydrophobic core of the chylomicron

– hydrophobic molecules are inside – TGs, cholesterol esters (adding FA to –OH group)

– they are released into lymph system

Question 15

What are apolipoproteins?

Answer 15

– they help dock chylomicrons

Question 16

How are lipoproteins classified?

Answer 16

– they are classified by density, as measured by centrifugation

– lipids are less dense than proteins, so the lipid content is inversely related to its density

– all share common structual features of chylomicrons

Question 17

T or F, proteins are more dense than lipids

Answer 17

True; Proteins are more dense, so a lipoprotein with a higher ratio of proteins to lipids, will be of higher density.

Question 18

Rate the different lipoproteins from least dense to most dense

Answer 18

– Chylomicrons are the least dense, with the highest ratio of lipids to proteins,

– Very Low-Density Lipoproteins (VLDL),

– Intermediate-Density Lipoproteins (IDL)

– Low-Density Lipoproteins (LDL)

– High-Density Lipoproteins (HDL).

Question 19

What is the purpose of lipoproteins?

Answer 19

– Each lipoprotein has specific protein components, called apolipoproteins, which bind to and help solubilize hydrophobic lipids in the blood for easy transport of lipoprotein complexes to specific locations in the body.

Question 20

What is the purpose of the binding of chylomicrons to surface of capillary?

Answer 20

• dietary fat is transported from intestine to peripheral tissues via chylomicorns

– VLDLs transport fat synthesized in lives

– TGs in these lipoproteins are hydrolyzed on capillary wall by lipoprotein lipase, which is activated by Apo-C-II

Question 21

Aside from activating the hydrolyzation of TGs what else does ApoC-II do?

Answer 21

– docks chylomicrons to the lipases

Question 22

Where do released fatty acids go?

Answer 22

– can be absorbed by surrounding tissues or become complexed with serum albumin to be further transported

Question 23

What do the lipases sitting w/ in our capillary walls do?

Answer 23

– the lipases are going to hydrolyze the triglycerides

– broken apart to pass through plasma membrane bc it’s too big

– can be broken down to diglycerides or monoglycerides

Question 24

Describe liver control of lipoprotein transport pathways.

Answer 24

– hydrolysis of TG of chylomicrons and VLDLs, results in protein and cholesterol “remnants,” which are taken up by liver and further degraded

– Apo-B-100 is resued to synthesize LDLs by liver

– LDL are primarily used to transport cholesterol to tissues, where aHDL transports excess cholesterol back to lives

– HIGH LDL levels associated with heart disease

Question 25

What is a summary of the fates of chylomicrons and VLDL?

Answer 25

– Chylomicrons and VLDL (triglyceride-rich) deliver TAG to cells in the body.

– Lipoprotein lipase digests the TAG to fatty acids and monoglycerides

– which can then diffuse into the cell to be oxidized, or in case of an adipose cell, to be re-synthesized into TAG and stored into cell

Question 26

T or F, VLDLs are very similar to chylomicrons

Answer 26

True; only difference is because they’re packaging tricoglycerol from the liver

Question 27

What is a summary of the fates of LDLs?

Answer 27

– LDLs (made up of apo b and cholesterol as well) delivers cholesterol to cells in the body

– VLDL particles are stripped of triacylglycerol, they become more dense and transformed into LDL

– cells take up cholesterol by receptor-mediated endocytosis

Question 28

What is a summary of the fates of HDL?

Answer 28

– HDL is involved in reverse cholesterol transport

– excess cholesterol is eliminated from the body via the liver, which secretes cholesterol in bile or converts it to bile salts

– liver removes LDL and other lipoproteins from the circulation by recepto-mediated endocytosis

– excess cholesterol can be used to make more hormones

Question 29

Describe receptor-mediated endocytosis of LDL

Answer 29

– cholesterol is obtained by tissues from dietary cholesterol and liver-synthesized cholesterol

– excess LDL cholesterol accumulates on arterial walls, attracting white blood cells

– if levels are too high to be removed, macrophages become engorged and harden into plaques (atherosclerosis), blocking blood vessels and can cause heart attack

– LDLs are taken up from blood by receptor-mediated endocytosis via the LDL receptor — LDL w/ receptor will undergo endocytosis

Question 30

What is the structure of a clathrin-coated pit?

Answer 30

– receptors are clustered in a structure called a “coated pit,” an invagination with an intracellular protein called clathrin

– Clathrin is a protein that plays a major role in the formation of coated vesicles

– it forms a triskelion shape composed of three clathrin heavy chains and three light chains

– clathrin interacts with itself, forming a cage, bringing large extracellular molecules into the cell

Question 31

Describe the process of receptor-mediated endocytosis of LDL.

Answer 31

– LDL receptors are synthesized in ER, matured in Golgi and go to cell surface in coated pits

– LDL binds via Apo B-100 to LDL receptor, is internalized endocytic vesicles, which form endosomes

– fuse with lysosome hydrolytic enzymes and proton pumping lowers pH and dissociates LDL from receptors

– free cholesterol, amino acids and cholesterol esters

– receptors are recycled to surface

Question 32

What happens once cholesterol is released?

Answer 32

– it can’t move on it’s own so it goes to ER or golgi and is packaged to transported

Question 33

Where is clathrin and LDL receptors located?

Answer 33

– Clathrin proteins are on the cytoplasmic side while LDL receptors are on external side

Question 34

Why can cholesterol build up even when there are LDL receptors?

Answer 34

because there are only so many LDL receptors that we have in our bodies

Question 35

Describe the process of mobilization of stored fat for energy (lipolysis).

Answer 35

– hydrolysis of TG to Glycerol and Fatty acids is hormonally regulated in a comparable way to mobilization of glycogen

– enzymes involved in lipolysis are activated by glucagon, epinephrine, parathyroid hormone, thyrotropin, etc.

– Free fatty acids enter blood stream and bind to serum albumin and taken up by tissues as needed

– glycerol is take up mostly by liver for gluconeogenesis

Question 36

How can fat act as a source of ATP?

Answer 36

– fat oxidation and ATP production is fairly simple because it feeds into the TCA cycle and electron transport systems

– it converges with the glucose oxidation system at the Acetyl-CoA step

Question 37

Describe how FFA are used as a source of ATP.

Answer 37

— FA come from biosynthesis in cell

— FFA are released from cellular Triacylglycerols by hydrolysis

— Free FA come from adipose tissue and also enter cells by lipase attack on chylomicrons

– Free FA are carried by serum albumin. They diffuse into cells or enter via FA transporters

– FA oxidation occurs in mitochondria

– During conversion to acetyl-CoA, FA is in the form of acyl-CoA

– two C atoms are removed at a time, in the form of acetyl-CoA (Beta oxidation)

Question 38

Describe the activation of fatty acids.

Answer 38

– inner mitochondrial membrane is impermeable to long-chain fatty acids (>10 carbons) and acyl-CoA

– so a transport system is used concurrently with activation to initiate Beta oxidation pathway

Question 39

What is the carnitine shuttle?

Answer 39

– responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation

Question 40

Describe the transfer of long-chain Fatty acyl groups from CoA to Carnitine and back.

Answer 40

– The exchange is mediated by carnitine acyltransferase I located in the outer membrane (separate from shuttle)

– transferred to the matrix via translocase

– carnitine acyltransferase II (catalyzes shuttle of carnitine) transfers the FA back to CoA and releases carnitine

Question 41

How many carbons are removed during one round of Beta oxidation?

Answer 41

– 2 carbons and produces acetyl-CoA

– Fatty acid is a 16 carbon molecule –> so there’s 7 rounds that are done which releases 7 NADH and 7 FADH2 (instead of 8 bc on last round there wouldn’t be an even number of carbons to split it into 2 carbons)

– remember: biological oxidation usually involves the loss of electrons, addition of water, removal of hydrogen, or the addition of oxygen

Steps:

1. Dehydrogenation
2. Hydration
3. Dehydrogenation
4. Thiolytic cleavage

Question 42

What does Beta oxidation tell us?

Answer 42

– tells us that the the beta carbon is oxidized (C3)

– this is very similar mechanism to oxidizing succinate in CAC

– cleaved by CoA-S-H, splitting of 2C into acetyl-CoA (thiolase)

8 total Acetyl-CoA produced from one FFA

Question 43

What is beta-oxidation?

Answer 43

– beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the mitochondria in eukaryotes to generate acetyl-CoA,

– which enters the citric acid cycle,

– and NADH and FADH2, which are co-enzymes used in the electron transport

Question 44

What is ketogenesis and ketone bodies?

Answer 44

– happens in starvation when glucose levels are too low

– if fatty acid metabolism is very rapid, as in untreated Diabetes or starvation: acetone, acetoacetate and beta-hydroxybutyrate are formed from excess acetyl-CoA that can’t be processed by TCA cycle –> Ketone Bodies

– Brain can use ketone bodies for 1/2 energy needs –> can be made by the liver

Question 45

What do insufficient ketogenesis and excessive production of ketone bodies cause?

Answer 45

– insufficient ketogenesis can cause hypoglyemia

– whereas excessive production of ketone bodies if left untreated can lead to ketoacidosis –> leads to decreased blood pH –> dangerous

– acetone gives a characteristic sweet smell to breath of people in ketoacidosis –> bc they have an accumulation of sugar

Question 46

How are ketone bodies used for fuel by the brain?

Answer 46

– ketone bodies pass through blood barrier then pass through inner membrane

– water soluble

– source of fuel for brain, heart, and muscle

– major energy source (75%) for brain during starvation

Question 47

T or F, Acetyl-CoA is a key intermediate between fat and carbohydrate metabolism

Answer 47

True; Acetyl-CoA can be made back into fatty acids