Structure And Functions Of Fatty Acids And Triacylglycerols

Question 1

Fatty acids

Answer 1

. Long chain (16-24c) carboxylic acids
. Saturated, monounsaturated, or polyunsaturated (omega-3/omega-6) w/ cis double bonds
. Essential fatty acids can’t be synthesized in humans

Question 2

Triglycerides

Answer 2

3 fatty acids esterified to glycerol

Question 3

Fatty acid functions

Answer 3

. Metabolic fuel that generate ATP during oxidation w/in mitochondria
. Metabolized to water soluble ketones in liver to be used as alternative fuel
. Involved in cell signaling process and components of structural lipids

Question 4

Fatty acids biosynthesis locations

Answer 4

. Liver

. Lactating mammary glands

Question 5

Rate limiting /regulated step in fatty acid biosynthesis

Answer 5

. Acetyl-CoA carboxylated to form Malonyl -CoA via acetyl-CoA carboxylase 1 (ACC1)
. ACC1 lipgenic enzyme in cytosol
. Biotin-dependent
. Requires ATP

Question 6

Fatty acid synthase

Answer 6

. Multienzyme complex w/ 6 enzymatic domains
. Catalyzes stepwise formation of palmitic acid from malonyl-CoA
. Adds 2C units from malonyl CoA to form palmitic acid (16-C fully saturateD)
. 2 NADPH required
. Rxn: 8 acteyl-CoA (2C) + 7 ATP + 14NADPH -> palmitic acid [16:0]
. Needs

Question 7

Other long-chain fatty acids formed from palmitic acid through ____

Answer 7

Elongation and desaturation rxns

Question 8

Translocation of acetyl CoA from mitochondrial matrix. To cytosol

Answer 8

. Transported in form of citrate made by condensation of acetyl CoA and oxaloacetate by citrate synthase
. In cytosol, citrate is cleaved via ATP-citrate lyase to regenerate acetyl CoA

Question 9

Allosteric activation/inhibition of ACC1

Answer 9

. Inter conversion of active polymeric form of ACC1 w/ inactive protomeric (subunit) form of enzyme
. Pos.: citrate (promotes polymerization of ACC1)
. Neg: long-chain fatty acids (promote depolymerization)

Question 10

Reversible phosphorylation/dephosphorylation of ACC1

Answer 10

. Insulin stimulates phosphatase to dephosphorylate ACC1 to activate it

Question 11

AMP-activated protein kinase (AMPK)

Answer 11

. Activated by AMP
. Promotes phosphorylation and inactivity of ACC1
. When ATP low, AMP high, ACC1 inhibited

Question 12

Long-term regulation of ACC1

Answer 12

. Induction.inhibition of expression of ACC1 gene

. Regulated by dietary factors and hormones

Question 13

Fatty acid elongation

Answer 13

Malonyl-CoA is 2C donor permitting elongation of pamitoyl-CoA by enzymes in smooth ER

Question 14

Fatty acid desaturation

Answer 14

. Desaturase enzymes introduce cis-double bonds at carbons 4,5,6, and 9
. Most common desaturation btw C9-10 of palmitic acid and stearic (18:0) acid converting it to palmitoleic acid (16:1(9)) and oleic acid (18:1(9))
. need NADH and oxygen

Question 15

T/F humans can’t introduce double bonds beyond C9 position

Answer 15

T

Question 16

Essential fatty acids

Answer 16

. Linoleic acid (18:2(9, 12))
. Alpha-linolenic acid (18:3(9, 12, 15))
. Sometimes arachidonic acid (20:4(5,8,11,13)) but can technically be synthesized w/in body from linoleic acid

Question 17

Desaturation and elongation of alpha-linolenicacid produces ____

Answer 17

Eicosapentaenoic acid (20:5(5,8,11,14,17))
Docosahexaenoic acid (22:6(4,7,10,13,16,19))

Question 18

Desaturation and elongation of linoleic acid forms ____

Answer 18

Omega-6 family of long-chain polyunsaturated acids

Question 19

Alpha-linolenic acid desaturation and elongation creates ___

Answer 19

Omega-3 family

Question 20

Substrates for pro- and anti-inflammatory eicosanoids

Answer 20

. Arachidonic acid (ARA)
. Eicosapentaenoic acid (EPA)
. These along w/ docosahexaenoic acid (DHA) accumulate in cell membranes in brain

Question 21

Storages of fatty acids as TAG

Answer 21

. Fatty acids in excess form triglycerides
. TAG packaged into VLDL particles and excreted into blood
. In muscle and adipose, lipoprotein lipase lipoprotein lipase hydrolyzes TAG present in circulating VLDL to release free fatty acids that are taken up into tissues and oxidized to form ATP or re-esterified to glycerol forming long-term energy reserve

Question 22

Limiting step of fatty acid oxidation and how is it regulated?

Answer 22

Carnitine shuttle by malonyl-CoA

Question 23

Lipases used in intracellular lipolysis

Answer 23

. Adipose triglyceride lipase (ATGL)
. Hormone-sensitive lipase (HSL)
. Monoglyceride lipase (MGL)

Question 24

How is low lipase activity in fed state achieved?

Answer 24

. ATGL not accos. W/ cofactors protein CGI-58 (complexed w/ perilipin A)
. HSL localized to cytosol

Question 25

What occurs when lipolysis is stimulated in fasted state w/ lipases

Answer 25

. Phosphorylation of perilipin A and HSL . CGI-58 dissociates from perilipin and assoc. w/ ATGL to be fully active . HSL activates and migrates to surface of lipid droplet where it assoc. w/ perilipin A

Question 26

In fasted state, fatty acids released from adipocytes bind to ___

Answer 26

Albumin and are transported in blood to tissues

Question 27

After transport into cells, how are fatty acids activated?

Answer 27

. Converted to fatty acyl-CoA by long-chain fatty acyl-CoA synthase that is assoc. w/ outer mitochondrial membrane . Needs ATP to do this

Question 28

Carnitine shuttle

Answer 28

. Translocates fatty acids from cytosol to mitochondrial matrix . Carnitine acyltransferse (CAT-1) on outer mitochondrial membrane transfers fatty acyl group from CoA to Carnitine . Complex migrates through intermembrane space and inner mitochondrial membrane . Carnitine acyltransferase II (CAT-II) releases fatty acid from carnitine and regenerates activated fatty acyl-CoA . Rate limiting step of beta-oxidation

Question 29

T/F short and medium chain fatty acids (4-12C) enter mitochondria w/ carnitine shuttle

Answer 29

F, have independent mechanism

Question 30

Mitochondrial beta-oxidation

Answer 30

. Long-chain fatty acids oxidized through repeating series of 4 rxns of beta-oxidation . Each cycle of beta-oxidation releases acteyl-CoA and generates FADH2 and NADH Net: palmitoyl-CoA + 7FAD + 7H2O + 7NAD + 6CoA -> 8 acetyl-CoA + 7FADH2 + 7NADH + 7H (each cycle has 1 FADH2, NADH, and Acetyl CoA)

Question 31

MCAD deficiency

Answer 31

. Medium-chain acyl-CoA dehydrogenase (MCAD) is most common inborn error of fatty acid metabolism

Question 32

Ketone body location

Answer 32

. Fatty acids in liver cells converted to ketone bodies for metabolic fuel for non-hepatic tissues including brain

Question 33

How are fatty acids metabolized in muscle?

Answer 33

, metabolized to CO2 and H2O via beta-oxidation and TCA to generate ATP

Question 34

Ketogenesis in hepatocytes

Answer 34

. During extended fast . Acetyl-CoA from fatty acid oxidation exceeds capacity of TCA to oxidize it to CO2 and H2O . 3 Acetyl-CoA forms HMG CoA in mitochondria . HMG-CoA forms acetoacetate . Some Enters blood directly as fuel, most are reduced to beta-hydroxybutyrate (major ketone) . Some acetoacetate spontaneously decarboxylates to acetone in blood which is excreted

Question 35

Ketolysis in peripheral tissues

Answer 35

. Beta-hydroxybutyrate and acetoacetate transported into mitochondrial matrix . Converted back to acetyl CoA . Catabolized by TCA cycle to generate ATP

Question 36

Enzyme that converts acetoacetate to acetoacetyl-CoA during ketolysis and where is is absent?

Answer 36

. SCOT enzyme . Also called mitochondrial thiophorase . NOT in liver so liver can’t use fatty acids as fuel

Question 37

Ketogenic amino acids

Answer 37

. Leucine and lysine | . Catabolism of carbon skeletons leads to ketone bodies

Question 38

If fatty acid has more than one double bond, they are spaced at ___ carbon intervals

Answer 38

3 carbon intervals

Question 39

Amount of contribution that biosynthesis of TAGs

Answer 39

Small because it is inefficient

Question 40

DHA and ARA have roles in ___

Answer 40

. Brain development . Cortical visual acuity . Cognition . Infant development

Question 41

TAG formation

Answer 41

Glycerol phosphate + 3 acyl CoA + H2O -> TAG + 3 CoA + P

Question 42

ROle of ACC2 in regulation of fatty acid oxidation

Answer 42

. On outer mitochondrial membrane | . Makes malonyl CoA from acetyl CoA that inhibits CAT1 stopping fatty acid oxidation

Question 43

Net ATP from one palmitic acid

Answer 43

129 ATP