Macro Nutrients - Lipid

Front 1

QUESTION (1)

Name the 9 classifications of Lipids and give examples.

Back 1

1. Hydrocarbons (only H & C)

2. Substituted Hydrocarbons (the following may be substituted on lipid alcohol, aldehyde, FAs, amines)

3. Fats & Most Oils (mono, di, triglycerides)

4. Compound Fat (esters of FAs with alcohol, FA, and misc
Phospholipids (phosphotidyl...)
Sphingolipids
Lipoproteins
Glycoproteins (misc - CHO)

6. Derived Fats (glycerol, steroids, cholesterol, hormones, etc)

7. Plant Steroids

8. Other Fats (fat soluble vitamins, eicosanoids etc)

9. Saturated & Unsaturated (saturated = no double bonds, unsaturated = double bonds)
16:0 means 16 carbons and 0 double bonds

Front 2

QUESTION (1)

Describe the functions of fat.

Back 2

1. triglycerides are the most efficient form of stored fat for use as energy

2. Saves space, contains less oxidized material than glycogen

3. Used to form other lipids (cholesterol, phospholipids)

4. Padding for skeleton & organs

5. Temperature insulation

6. Phospholipids & cholesterol are integral parts of cell membranes

7. Fatty acids synthesizes prostaglandins, leukotrienes, and thromboxanes

8. Chlolesterol is used to form steriod hormones & vit D

9. Fat contains essential fatty acids

Front 3

QUESTION (1)

1. Describe the triglyceride structure

2. What is the main purpose of storing triacylglycerides?

3. Where are triacylglycerides stored?

4. What is the major building block used in triacylglyceride synthesis?

Back 3

1. glycerol backbone & 3 fatty acids with ester bond

2. for future use of the fatty acids

3. in all cells, but mainly in adipocytes

4. glycerol in all tissues except adipocytes

adipocytes use DHAP instead because they lack glycerol kinase (means they must have glucose for glycolysis to store fatty acids)

Front 4

QUESTION (1)

1. Describe the phospholipid structure.

Back 4

1. Glycerol backbone with 2 fatty acids attached, the 3rd position has a phosphate and a misc attachment

2.

Front 5

QUESTION (1)

1. Name the phospholipids PC, describe what they are used for, and what is attached in each position.

2. Name and decribe a pseudoPC.

3. Name the phospholipids PE, describe what they are used for, and what is attached in each position.

Back 5

1. Phosphotidylcholine
1st Palmitic (or) stearic
2nd Oleic (or) linolenic (or) linolenic
3rd Choline
These are known as lecithins

2. dipalmitoyllecithin is not a true phosphotidylcholine, but has choline in 3rd position, a pulmonary surfactant, significant cause of death in premies "respiratry distress syndrome (RSD)

3. Phosphotidylethanolamine
1st palmitic (or) stearic
2nd long chain polyun
3rd ethanolamine

Front 6

QUESTION (1)

1. What do phospholipases do?

2. What specifically does phospholipase A2 do?

3. What is a plasmalogin?

4. Describe the structure of a sphingolipid, name the 2 major groups.

Back 6

1. They release fatty acids from triacylglycerides. Different forms A1, A2, C, and D are all specific to locations on each fatty acid attachment

2. Releases arachidonic acid from the C-2 position of membrane phospholipids (glucocorticoids inhibit)

3. A phospholipid
1st ether-linked alcohol (instead of a ester-linked fatty acid)
2nd & 3rd resemble phosphotidylcholine
Found in myelin sheaths of nerve fibers, cell membranes of muscle, and platelets
Example: Plately Activating Factor (PAF)

4. backbone is sphingosine (derived from glycerol), 2 majorgroups include sphingomyelins & glycosphingolipids (cerebrosides, sulfatides, globosides, gangliosides)

Front 7

QUESTION (1)

1. What factors have a negatve correlation with coronary heart disease (CHD)?

2. How does n-3 PUFA protect against atherosclerosis?

Back 7

1.
* Monounsaturated fat intake
* Polyunsaturated fat intake (both n-3 & n-6)
* Linoleic Acid (n-6, 18:2) in adipose tissue has inverse relationship with CHD risk
* n-3 Polyunsaturated fat has anti-atherogenic properties

2.
* interferes with platelet aggregation by inhibiting TXA2 (ALA, EPA, DHA equal in effect)
* reduction in release of pro-inflammatory cytokines during fatty plaque formation
* sharp decrease in triglyceride concentration

Front 8

QUESTION (1)

1. Which fatty acids are known to be hypercholesterolemic?

2. Which fatty acid is known to neutral in terms of raising cholesterol?

3. Which fatty acids are known to be hypocholesterolemic?

Back 8

1. Lauric, Myristic (worst), Palmitic....all raise LDLC

2. Stearic acid (18:0, saturated)

3. Oleic acid, Linoleic (best).....lowers total & LDL cholesterol

Front 9

QUESTION (3)

1. Describe the 8 steps involved in lipid digestion

Back 9

1.
1) Mouth
* digestion of short & medium chain triglycerides
*chewing - emulsification
* lingual lipase (active role in infants to digest SCFA & MCFA)
2) Stomach
* digestion of short & medium chain triglycerides
* churning emulsification
* gastric lipase
3) Small Intestine - Emulsification
* fat enters SI & triggers CCK to release bile salts
*Micelles are formed
* Pancreatic lipase & intestinal lipase TG → MG, glycerol, FA
4) Small Intestine - Digestion
* After emulsification, pancreatic lipase, cholesterol esterase, and phospholipase A2 release FAs from triglyceride
5) Enterocytes/Brush Border -* monoglycerides & fatty acids are absorbed by breaking down triglycerides into absorbable forms 2-MAG, 1-MAG, and glycerol
6) Inside Enterocyte - * monglycerides & free fatty acids are reassembled (re-esterified) into triacylglycerides
7) Interstitial Fluid
* triglycerides are used to form chylomicrons
8)Lymph & Blood - chylomicrons diffuse into lymph and then blood

Front 10

QUESTION(3)

1. What does bile contain?

2. Describe the structure of bile.

3. Are bile acids or bile salts found in the small intestine after a fatty meal?

Back 10

1. phospholipds, cholesterol, bile acids (cholic acid)

2. One end has an AA side chain that is hydrophilic, the other end has a sterol that is hydrophobic.

3. Bile salts (after bile acids are conjugated they become bile salts)

Front 11

QUESTION (3)

1. Describe the 4 steps involved in breaking down triacylglycerol.

2. What happens to the various pieces of the triglyceride once they get absorbed?

Back 11

1.
1) pancreatic lipase removes FA #3
triacylglycerol → 1,2-diacylglycerol

2) pancreatic lipase removes FA #1
1,2-diacylglycerol → 2-monoacylglycerol (2-MAG)

3) Isomerase moves the #2 FA to the #1 position.
2-MAG → 1-MAG

4) Pancreatic Lipase removes FA #1
1-MAG → glycerol

2.
1,2-diacylglycerol: pancreatic lipase to form 2-MAG

2-MAG: Monoacylglycerol pathway (or) to isomerase enzyme

1-MAG: enters into Phosphatidic Acid Pathway (or) to pancreatic lipase for removal of last FA, glycerol/FA enter separately

Glycerol: goes straight through

Front 12

QUESTION (3)
1. What is LPL, where is it found, and what does it do?

2. What happens after LPL removes FAs?

3. How do the chylomicron remnants get into the liver?

Back 12

1.
*Lipoprotein lipase
* Found on the endothelial cells of capillaries in adipose tissue and muscle
* Removes fatty acids from the triglycerides in chylomicrons

2.
* FAs are absorbed by tissues
* glycerol is sent back to liver & kidneys
* left over chylomicron remnants (contain apoE, apoB48, & cholesterol esters) are sent to the liver

3. The hepatic remnant receptor requires apoE to trigger endocytosis of the CMR

Front 13

QUESTION (3)

1. What is the rate limiting step in fatty acid synthesis?

2. What affects the activity of this enzyme?

3. Describe the steps involved in breakdown of triacylglycerides via hormone-sensitive lipase.

Back 13

1.
bicarbonate + acetyl-CoA + ATP → {Biotin & ACC} → malonyl-CoA

ACC = Acetyl-CoA carboxylase

2.
DECREASED ACTIVITY
cAMP/PKA (glucagon/EPI) → phosphorylation of specific serine residues in ACC

INCREASED ACTIVITY
PKA-independent (insulin) → phosphorylation of different nonserine residues

3.
* EPI binds with a beta-adrenergic receptor
* G protein activates Adenylate Cyclase
* ATP + Adenylate Cyclase = cAMP
* cAMP activates PKA
* ATP + PKA phosphorylate hormone-sensitive lipase
* Hormone-sensitive lipase acts on triacylglycerides (TAG) & DAG to release FAs
* MAG lipase (only in hormone-sensitive response) releases FA from MAG

Front 14

QUESTION (3)

1. What is a lipoprotein?

2. What are they used for?

3. Name the major types of lipoproteins.

4. What are the major classes of apoproteins and where are they synthesized?

Back 14

1. Lipoproteins = apoproteins + lipid (cholesterol esters, TG, phospholipids, free cholesterol)

2. To carry lipid in the blood

3. Chylomicrons, Very-Low Density-Lipoprotein (VLDL), Low-Density Lipoproteins (LDL), & High-Density Lipoproteins (HDL)

4.
apoA - liver & intestines
apoB - liver & intestines
apoC - liver
apoE - liver & peripheral tissues

Front 15

QUESTION (3)

1. Chylomicrons carry exogenous or endogenous lipid?

2. Which apoproteins do chylomicrons have?

3. What happens when the chylomicrons reach the capillaries of the adipose tissue?

4. What is a chylomicron remnant and what apoproteins do they have?

5. What happens to glycerol once it reaches the liver & kidneys?

Back 15

1. exogenous

2.
* apoB-48
* apoC-II (activates LPL in the presence of phopholipid)
* apoE

3.
* apoC-II activates LPL and free fatty acids are removed from TAGs
* FAs are absorbed by tissues and glycerol backbone is sent to the liver & kidneys
* during this removal of FA, phospholipid, apoA, and apoC are transfered to HDL

4.
* after the chylomicron transfer to HDL, it cannot further degrade without apoC-II
* remaining portion is the "chylomicron remnant"
* apoB-48

5. Glycerol is converted to DHAP

Front 16

QUESTION (3)

1. What are VLDLs and what are they used for?

2. What apoproteins do they have?

3. How do they deliver FAs to tissues?

4. What is left after most of the FAs have been released?

5. Where do IDLs go?

Back 16

1.
* VLDLs are molecules designed to transport endogenously derived TAGs to adipose and muscle tissues most commonly
* the endogenous TAGs came from excessive FAT & CHO intake, liver converted to TAGs for storage or energy

2. apoB-100, apoC-II

3. They use apoC to activate LPL just like chylomicrons do

4.
* Intermediate density lipoproteins (IDL) are left over
* also called "VLDL remnants"

5.
* IDLs can become LDLs if more TAGs are removed
* they can be taken up by the liver via LDL receptor w/apoB-100 & apoE

Front 17

QUESTION (3)

1. What are LDLs and what do they do?

2. What apoproteins do LDL have and what is it used for?

3. What happens once an LDL receptor allows the endocytosis of the LDL into the cell?

4. What does the cell do with excess intracellualr cholesterol?

Back 17

1.
* LDLs come from IDLs via LPL removal of TAGs
* primary cholesterol carriers for delivery to all tissues

2.
* apoB-100
* required for interaction with LDL receptors

3.
* apoproteins are degraded
* cholesterol esters are hydrolyzed to yield free cholesterol
* cholesterol is incorporated into membrane

4.
acyl-CoA-cholesterol acyltransferase (ACAT) re-esterifies it for intracellular storage

Front 18

QUESTION (3)

1. What is HDL?

2. Where do HDLs come from?

3. What apoproteins do HDL have?

4. What does HDL do?

Back 18

1.
* protein-rich disc-shaped particles

2. The liver & SI synthesize de novo

3. apoA-1 & apoE (from macrophages)

4.
* HDL is designed to gather free cholesterol from the periphery and deliver it to the liver
* free cholesterol in IDLs is esterified by the HDL enzyme lecithin-cholesterol acytransferase (LCAT), which requires apoA-1
* removes excess cholesterol from cells and transfers it back to liver for bile
* macrophages take up HDL via apoA-1, allows HDL to remove cholesterol & apoE from macrophages, once HDL is full of cholesterol it is secreted from the macrophages with the apoE to allow entery to the liver

Front 19

QUESTION (3)

1. What is lipoprotein X (Lp-X)?

2. What is Lipoprotein A (Lp(a))?

Back 19

1.
* an abnormal form of LDL that predominates in paients with lecithin-cholesterol acyl transferase (LCAT) deficiency (or) cholestatic liver disease
* elevated circulating free cholesterol and phospholipids

2.
* a genetic varient of LDL that includes an apoA protein
Lp(a) = LDL + apoA
* Lp(a)'s function is not known, but may be linked to lipid transport and blood-clotting
*apo(a) is plasmiogen-like and may result in Lp(a)delivering cholesterol to an injured/inflammed area & sudden clot development
* Positive correlation with premature heart attacks
* an independent genetic risk factor for atherosclerosis

Front 20

QUESTION (3)

1. Where does apoE come from?

2. What does apoE do?

3. Would an apoE genetic defect affect lipid metabolism?

Back 20

1.
* liver makes it from VLDLs
* it is released from IDLs
* macrophages release it to HDLs
* brain and most other tissues synthesize without VLDL

2.
* acts as a secret code for tissues to take up cholesterol

3. it seems like it would, but has not been demonstrated
*

Front 21

QUESTION (3)

1. Describe the 8 steps involved in uptake of cholesterol via LDL receptors.

Back 21

1.
1) apoB-100 & LDL receptors attach to cell

2) clathrin coated pits form

3) clathrin facilitates LDL endocytosis

4) sorting endosome is formed by combining the LDL vesicle with a vesicle (pH of 5.0)

5) acidity causes LDL to release from receptor, receptor is recycled

6) LDL & cholesterol esters accumulate in transport vesicles (vesicle without LDL receptor)

7) transport vesicle fuses with a lysosome in the cell, the apoB-100 protein is degraded, free cholesterol is released

8) free cholesteral moves to the golgi apparatus for storage

Front 22

QUESTION (3)

1. What two genetic problems can lead to familial hypercholesterolemia?

Back 22

1.
* genetic mutations in either the LDL receptor or the apoB-100 protein can lead to excess cholesterol circulating in the blood because it can't be taken up by the cells
* leads to atherosclerosis, excess cholesterol is deposited in the skin, tendons, and arteries

Front 23

QUESTION (4)

1. Where does cholesterol synthesis occur in the cell, and how much do the liver and intestines make?

2. Of total body cholesterol, how much is produced de novo?

3. What are the 6 major steps of cholesterol synthesis

4. Where does the acetyl-CoA come from to start cholesterol synthesis?

5. How does actyl-CoA get into the cytoplasm?

Back 23

1.
* cytoplasm & microsomes
* liver 10% & intestines 15%

2. slightly less than 1/2

3.
1) 2acetyl-CoA → {thiolase} → acetoacetyl-CoA + CoA-SH

2) acetyl-CoA + acetoacetyl-CoA + H2O → {HMG-CoA synthase}→ HMG-CoA

3) HMG-CoA + 2NADPH → {HMG-CoA reductase} → mevalonate

4) mevalonate + ATP → {decarboxylation, loses CO2} → IPP

5) IPP + NADPH → {squalene synthase} → squalene

5) squalene → cholesterol

4. β-oxidation in the mitochondria produces the acetyl-CoA

5. acetyl-CoA is transported to the cytoplasm in the form of citrate
citrate + ATP → {ATP-citrate lyase} → OAA + acetyl-CoA

Front 24

QUESTION (4)

1. Describe the 3 mechanisms involved in controlling cholesterol levels in the body (de novo synthesis).

2. Describe the 3 mechanisms used to regulate HMG-CoA reductase.

3. What factors increase or decrease phosphorylation?

Back 24

1.
* regulation of HMG-CoA reductase (primary)
* regulation of excess intracellular free cholesterol, acyl-CoA-cholesterol acyltransferase (ACAT)
* regulation of plasma cholesterol levels via LDL (apoB-100) & HDL (apoA-1 & apoE)

2.
* control of gene expression (excess cholesterol downregulates)
* rate of enzyme degradation (when cholesterol is abundant HMG-CoA reductase is degraded)
* phosphorylation (decreases activity) & dephosphorylation

3.
* insulin ↑ cholesterol synthesis by dephosphorylating HMG-CoA reductase (active)
* insulin ↓ cAMP, which DECREASES activation of PP-I & PP-I is less likely to block dephosphorylation

* glucagon & EPI ↓ cholesterol synthesis by keeping HMG-CoA reductase phosphorylated (inactive)
* glucagon & EPI ↑ cAMP, which INCREASES PP-1 and blocks dephosphorylation of HMG-CoA reductase

(inhibitor of HMG-CoA reductase phosphatase, protein phosphatase 2C, phosphoprotein phosphatase)
* glucagon & EPI
to dephosphorylate AMPRK, which then is active and can dephosphorylate HMG-CoA reductase.

Front 25

QUESTION (4)

1. How is liver-synthesized cholesterol and excess dietary cholesterol transported in the blood?

2. What is the last thing

Back 25

1.
* The liver makes VLDLs
* the de novo & excess dietary cholesterol are added to the VLDLs to form LDLs
* the enzyme used to do this is called "endothelial cell-associated lipoprotein lipase"

Front 26

QUESTION (4)

1. How is excess cholesterol excreted?

2. Name the 2 most abundant bile acids.

3. How does a bile acid become a bile salt?

4. Name the 4 bile salts.

5. What happens to the bile salts in the small intestine?

Back 26

1. Excess cholesterol is used to form bile acids in the liver (not adequate for excreting excess dietary cholesterol)

2.
* chenodeoxycholic acid 45%(inhibits HMG-CoA reductase) * cholic acid 31%

3. conjugation of carboxyl end with either glycine or taurine before being secreted into the bile canaliculi

4.
* Glycocholic Acid (glycine + cholic acid)
* Taurocholic Acid (taurine + cholic acid)
* Glycochenodeoxycholic Acid (glycine + chenodeoxycholic acid)
* Taurochenodeoxycholic Acid (taurine + chenodeoxycholic acid)

5. Taurine & glycine are removed and then the bile acids are either excreted (very small %) or reabsorbed via "enterohepaic circulation"

Front 27

QUESTION (4)

1. Describe the 4 physiologically significant functions of bile acid synthesis.

2. Which steroid hormone is the only one not made of cholesterol?

3. What is the first step in the conversion of choleserol to steroid hormones?

Back 27

1.
* sythesis & excretion in feces is the only significant mechanism to eliminate excess cholesterol

* they solubulize cholesterol in the bile and prevent precipitation/gallbladder stones

* they facilitiate digestion of TAGs by acting as an emulsifier to make them accessible to pancreatic lipase

* they facilitate the absorption of fat-soluble vitamins

2. retinoic acid

3.
* rate limiting & irreversible
* cholesterol (C27) → pregnenolone (C21) + isocaproaldehyde (C6)

Front 28

QUESTION (4)

1. Describe the function and source of the following:
pregnenolone
progesterone
testosterone
estradiol
aldosterone
cortisol

Back 28

1.
* pregnenolone - used to synthesize steroid hormones, from cholesterol

* progesterone - secreted by the corpus luteum, changes associated with luteal phase of menstral cycle, from pregnenolone

* testosterone - male sex hormone, secondary sex characteristics, from progesterone

* estradiol - principal female sex hormone, secondary female sex characteristics, from testosterone or DHEA

* aldosterone - main mineralocorticoid, synthesized in adrenal cortex , raises blood pressure & fluid volume, increases Na+ uptake, from progesterone

* cortisol - main glucocorticoid, synthesized in adrenal cortex, stress adaptation, elevates blood pressure & Na+ upatek, effects immune system, from progesterone

Front 29

QUESTION (4)

1. Describe the order of sex hormone synthesis.

Back 29

1.
Cholesterol
↓
pregnenolone → DHEA → estradiol
↓
progesterone
↓
testosterone → estradiol
↓
dihydrotestosterone

Front 30

QUESTION (4)

1. How does red yeast rice lower cholesterol?

2. What is one of the major precautions for taking red yeast rice?

3. What dangers are associated with taking statin drugs?

4. What are two additional supplements that help with cholesterol management?

Back 30

1.
* contains 9 different Monacolins that all inhibit HMG-CoA reductase
* also contains several plant sterols that compete for absorption with animal sterols

2. liver disease or drinking more than 2 alcoholic drinks per day may affect liver function, also taking it with statin drugs increases risk for overdose/liver damage because same effect

3. myalgia, muscle cramps, myopathy, arthritis, fever, chills, fatty liver changes in liver, cirrhosis, kidney problems.......red yeast rice does not have these side effects

4.
* Inositol hexanicotinate (IHN) - a nonflushing form of niacin (B3) that helps to remove excess cholesterol (or) decreases the deposit of cholesterol
* Coenzyme Q10 (CoQ10) - statins lower CoQ10, supplementing actually works synergistically with statins

Front 31

QUESTION (4)

1. How do plant sterols (sitosterol (main), campersterol, stigmasterol, sitostanol) help to lower cholesterol?

Back 31

1.
* plant sterols are different from cholesterol
* they have no double bonds and have a methyl or ethyl in their side chain
* not absorbed like cholesterol
* plant sterols compete with cholesterol to get mixed into a micelle
* plant sterols can't be absorbed, but for every one included in a micelle, a cholesterol doesn't get absorbed
* decreased cholesterol return to the liver stimulates upregulation of LDL receptors, which decreases serum cholesterol because more is taken up by the liver via LDL receptor
* can be taken with statins
* may interfere with carotenoid and α-tocopherol absorption

Front 32

QUESTION (4)

1. List several clincal recommendations for lowering cholesterol.

Back 32

1.
* dietary modifications - ↓cholesterol intake (animal products, ↑solublle fiber intake
* multiple vitamin for cofactors
* CoQ10 if taking statin drugs
* take inositol hexanicotinate (IHN) (can't take if taking statins)
* red yeast rice instead of statins
* plant sterols to decrease cholesterol absorption, increases LDL receptors & lowers serum cholesterol

Front 33

QUESTION (5)

1. What is the suggested consumption ratio of EFAs?

2. Why are the ω-3s and ω-6s considered essential?

3. How do we aquire EFAs in the diet?

Back 33

1. 5:1 - 10:1
US says 10:1
Canada & WHO says 5:1

2.
* Vertebrates lack the Δ12 and Δ15 desaturase enxymes
* vertebrates are incapable of forming double bonds beyond Δ9 and therefore can't make any of the EFAs


3.
* plants can synthesize EFAs
* vertebrates aquire EFAs by eating plants (leafy greens) or by eating animals that eat the plants (example fish or wild game)

Front 34

QUESTION (5)

1. Explain the delta and omega numbering systems of omega fatty acids.

Back 34

1.
* If the fatty acid is unsaturated, then either the delta system or the omega system will indicate the placement of double bonds
* The delta (Δ) system counts the double bonds from the carboxyl (COOH) end of the fatty acid, and lists the placement of all the double bonds. For example, linoleic acid, 18:2Δ9,12 contains 18 carbon atoms with 2 double bonds on the 9th and 12th carbons from the carboxyl end of the acid.
* The omega (ω or n-) system counts the double bonds from the methyl (CH3) end of the fatty acid, and only lists the first double bond. In the omega system, linoleic acid is 18:2n-6.
* after the first double bond, the remaining double bonds are always 3 carbons apart (for both n-3s and n-6s)

Front 35

QUESTION (5)

1. List food sources for the following omegas-3s:
alpha-linolenic acid (ALA)
eicosapentaenoic acid (EPA)
docosahexaenoic acid (DHA)

2. Should omega-3 supplements be taken with or without food?

3. Why should cod liver oil not be used as a supplement for omega 3s?

4. Which EFAs are included in infant formula and when did the FDA allow them to be included?

Back 35

1.
ALA - flaxseed, walnuts, canola, and their oils

EPA - fatty fish, crab, oysters, shrimp, eggs (enriched)

DHA - fatty fish, crab, oysters, shrimp, algae, eggs (enriched)

2. with food in divided doses if possible

3. cod liver oil contains significant amounts of vitamins A and D, to take enough as a supplement for omega-3s it increases the risk of overdosing on the fat soluble vitamins

4. In 2001 the FDA allowed DHA and arachidonic acid to be included in infant formula

Front 36

QUESTION (5)

1. What are eicosanoids and what is their physiological significance?

2. Why is consuming an appropriate balance/ratio of EFAs important in terms of eicosanoid production?

Back 36

1.
* derived from 20 carbon PUFAs
* 20 carbons PUFAs: Arachidonic acid (AA)- form series 2
EPA - form series 3
DGLA (derived from GLA) - form series 1
* inflammatory response stimulates metabolism of 20 carbon PUFAs via cyclooxygenase (or) lipoxygenase to form eicosanoids
* eicosanoids = prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs)

2.
* the 20 carbon (AA, EPA, DGLA) EFAs all compete for the same cyclooxygenase & lipoxygenase enzymes to start the metabolism process into either pro or anti inflammatory products
* series 1 middle
* series 2 pro-inflammatory
* series 3 anti-inflammatory

Front 37

QUESTION (5)

1. How are eicosanoids released from cell membranes?

2. List the order of eicosanoid metabolism to reach series 1, 2, and 3.

3. What does the cyclic pathway produce?

4. What does the linear pathway produce?

5. Name 2 drug classes that can block these pathways.

Back 37

1.
* phospholipases (phospholipase A2 is specific for arachidonic acid because AA is usually found in the 2nd FA position)

1.
* n-6: LA → GLA → DGLA → Group 1 → AA → Group 2

*n-3: ALA → EPA → Group 3

3.
Cyclic pathway: cyclooxygenase & peroxidase enzymes, produces PGs & TXs, example AA produces TXA2 pro-platelet aggregation

* Linear Pathway: 5-lipoxygenase enzyme, produces leukotrienes (LTA4 is the first step, induced by IFN-γ to form LTB4 a potent inflammatory agent)

5.
* NSAIDs block COX
* corticosteroid drugs block phospholipase A2

Front 38

QUESTION (5)

1. The COX pathway can convert EPA into what 2 products?

2. Name 3 stimuli for phospholipase A2 that would lead to increased AA metabolism.

3. What is the function of ALA?

4. What is the function of DHA?

4. What role does vitamin E play in PUFA metabolsm?

Back 38

1. EPA → PGI3 or TXA3

2. EPI, thrombin, bradykinin

3. precursor for long-chain EPA & DHA

4.
* high concentration in retina
* DHA plays important role in regeneration of rhodopsin, which is involved in converting light to vision
* required during retinal development for proper function
* protects neurons from apoptosis, may be related to effects of fluidity

4.
* vitamin E is a fat soluble antioxidant and prevents oxidation of PUFAs
* the more PUFAs the more vitamin E is required

Front 39

QUESTION (5)

1. Describe the process of EFA deficiency and point out any diagnositic markers.

2. Why is cow's milk linked to EFA deficiency?

3. Total Home Parenteral Nutrition must include which FAs to prevent EFA deficiency?

4. What disease is known to be associated with EFA deficiency?

Back 39

1.
* Linoleic & Arachidonic Acids are low in plasma
* eicosatrienoic acid (20:3 n-9) is an abnormal by-product of oleic acid desaturation & is a triene (3 double bonds) [DIAGNOSTIC]
* elevated triene/tetraene ratio = EFA deficiency
* EFA deficiency = eicosatrienoic acid 20:3 /arachidonate 20:4
* normal ratio = 0.1 - 0.2
* EFA deficiency = > 0.2

2.
* skim milk is low in linoleic acid and lead to growth failure in infants
* cow's milk has only 25% of the linoleic acid found in human milk

3. Linolenic Acid (n-3) & Lenoleic Acid (n-6)

4.
* cystic fibrosis
* increased eicosatrienoic acid (the bad n-9)
* decreased LA & DHA

Front 40

QUESTION (5)

1. Describe 5 clincally significant functions of prostaglandins.

2. What is the UL for n-6 PUFAs?

3. What adverse effects have been associated with overconsumption?

4. Describe the physiological significance of the following AA metabolites:
LTA4
TXA4
PGE2
PGI2

Back 40

1.
* PGE2 & PGE1 induce redness, heat, swelling, edema
* corticosteroids are used to treat reheumatoid arthritis, psoriasis, and eyes by bocking PG synthesis
* PGs have been used to terminate pregnancy in the 2nd trimester
* PGs may play a role in male fertility
* PGE, PGA, PGI2 are vasodialators

2. none set yet

3.
* EPA & DHA are associated with adverse effects on...
immune function
bleeding & increased risk of hemorrhagic stroke (reduced platelet aggregation & prolonged bleeding time)
oxidative damage (due to lipid peroxidation)

4.
* LTA4 - precursor for LTC4, LTD4, LTE4 (all of which trigger bronchioconstriction, vasoconstriction, contraction of smooth muscle, and are components of slow-reacting substance of anaphylaxis) & LTB4 (chemotactic agent, releases lysosomal enzymes, adhesion moelcule)

* TXA4 - platelet aggregation, vasoconstrictor, contraction of smooth muscle
* PGE2 - vasodialation, relaxes smooth muscle
* PGI2 - vasodialation, inhibits platelet aggregation

Front 41

QUESTION (2)

1. What are the 4 steps involved in converting FA into something the mitochondria can use for β-oxidation?

Back 41

1.
1) activation in the cytoplasm

FA + ATP + CoA →{acl-CoA synthase}→ Acyl-CoA + PPi + AMP

2) acyl-CoA passes through the outer mitochondrial membrane and joind carnitine

acyl-CoA + carnitine → {carnitine palmiloyl transferase I}→ Acylcarnitine

3) with the help of another enzyme it is able to pass through the inner mitochondral membrane

acylcarnitine → {carnitine acylcarnitine translocase} →
acylcarnitine

4) once inside it gets converted back to acyl-coA

acylcarnitine + CoA →{carnitine palmiloyl transferase II}→ acyl-CoA + carnitine

Front 42

QUESTION (2)

1. Calculating energy production using FAs involves determining how many turns of beta-oxidation will occur. How is this determined?

2. What are the ATP equivalent values assigned to FAD, NAD, and GTP?

Back 42

1. separate the chain into 2 carbon units and count the bonds between, odd #ed chains will have a 3 carbon propionyl-CoA unit at the end

2.
FAD = 2
NAD = 3
GTP = 1

Front 43

QUESTION (2)
ENERGY USING & ENERGY PRODUCING STEPS OF FA OXIDATION

1. Activation of FA

2. Carnitine Shuttle

3. β-oxidation

4. TCA

5. Propionyl-CoA

Back 43

1.
FA + 2ATP →{acyl-CoA synthase}→ acyl-CoA

2. no energy used or produced

3.
* acyl-CoA + FAD →{acyl-CoA dehydrogenase}→ trans-Δ-enoyl-CoA + FADH
* β-hydroxyl CoA + NAD →{β-hydroxy CoA} → 3-ketoacyl CoA + NADH

4.
* isocitrate + NAD →{isocitrate dehydrogenase}→ α-ketoglutarate + NADH
* α-ketoglutarate + NAD →{α-ketoglutarate dehydrogenase}→ sucinyl-CoA
* succinyl-CoA + GDP →{succinyl thiokinase}→ succinate
* succinate + FAD →{succinate dehydrogenase}→ fumerate + FADH
* malate + NAD →{malate dehydrogenase}→ OAA + NADH

5.
* proprionyl-CoA + ATP →{proprionyl CoA carboxylase & methylmalonyl CoA mutase} → succinyl-CoA
* succinyl-CoA + GDP →{succinyl thiokinase}→ succinate
* succinate + FAD →{succinate dehydrogenase}→ fumerate + FADH
* malate + NAD →{malate dehydrogenase}→ OAA + NADH

Front 44

QUESTION (2)

1. How are ketone bodies produced?

2. When CHO intake is low, what factor will lead to more ketoacids being produced?

3. What causes the fruity breath smell?

4. Where are the ketone bodies used for energy?

5. What is the most significant clinical ketosis condition called?

6. What causes this condition?

7. What is the danger of having too many ketone bodies in circulation?

Back 44

1.
* excessive beta-oxidation can produce more acetyl-CoA than the KREBS cycle can handle
* the extra acetyl-CoA gets converted to ketone bodies
* acetoacetate, beta-hydroxybutyrate, acetone

2.
* CHO intake produced OAA
* the KREBS cycle can only work with adequate OAA, which means the excess acytl-CoA will be turned into ketone bodies

3. acetoacetate can undergo spontaneous decarboxylation to acetone, which creates the sweet smell

4. extrahepatic tissues (heart & skeletal muscle especially) to preserve glucose for the brain

5. diabetic ketoacidosis (DKA)

6.
* reduced supply of glucose due to lack of insulin
* increased beta-oxidation due to high glucagon in circulation

7.
* ketone bodies are relatively strong acids and shift the blood pH
* many problems result, main concern is ability of hemoglobin to bind oxygen

Front 45

QUESTION (1)

1. Name the phospholipids PS, describe what they are used for, and what is attached in each position.

2. Name the phospholipids PI, describe what they are used for, and what is attached in each position.

3. Name the phospholipids PG, describe what they are used for, and what is attached in each position.

4. Name the phospholipids DPG, describe what they are used for, and what is attached in each position.

Back 45

1. Phosphotidylserine
1st palmitic (or) stearic
2nd long chain poly un
3rd serine

2. Phosphotidylinositol
1st stearic
2nd arachidonic
3rd inositol
involved in signal transmission for cell growth and differentiation (outside to inside communication)

3. Phosphotidylglycerol
Main function is percursor for diphosphotidylglycerols (DPG)
Found in mitochondrial membranes, surfactant, and a percursor for cardiolipin

4. Diphosphotidylglycerol
1st and 2nd positions are constantly remodeled as part of cell membrane
Found in mitochondrial membrane, surfactant, cardiolipin
Degraded by Phospholipases