Fatty Acid Catabolism

Question 1

Why are triacylglycerols best long-term storage fuel?

Answer 1

FA chains are highly reduced
yield 2x the energy of protein and carbs
don’t affect osmolarity due to hydrophobicity
relatively inert - low risk of undesirable reactions

Question 2

percent energy derived from beta oxidation in heart and liver
percent energy from fatty acids in TAGs

Answer 2

80% energy from heart and liver
FA contribute to 95% of energy from TAGs

Question 3

sources of fat
stored

Answer 3

autophagy, dietary fats, fats produced by liver
adipocytes, liver, ovaries, testes, adrenal cortex

Question 4

Overview of lipid digestion and transport

Answer 4

1) bile salts in small intestine emulsify fats by water soluble enzymes
2) intestinal lipases degrade triacylglycerols/diacylglycerol/monoacylglycerol into free FA and glycerol
3) FA and glycerol taken up into intestinal mucosa and reformed into TAG
4) TAGs + cholesterol + apolipoproteins combined into chylomicrons
5) chylomicrons travel in blood and lymph to tissues
6) Lipoprotein lipase oxidizes FA as fuel or re-esterified for storage

Question 5

Lipoprotein lipase is activated by

Answer 5

apoC-II in bloodstream to convert TAGs into fatty acid and glycerol
apoC-II dictates dropoff pathway through body

Question 6

Increasing density of lipid transport molecules (low to high)

Answer 6

chylomicrons (100-500nm diameter), VLDL, LDL, HDL, VHDL

Identification of different densities of molecules by ultra-centrifugation

Question 7

Apolipoprotein definition

Answer 7

Apolipoproteins are lipid-binding proteins in the blood that are responsible for the transport of triacylglycerols, phospholipids, cholesterol, and cholesteryl esters between organs

Apolipoproteins act as signals to for uptake and metabolism of chylomicron contents

Question 8

hormones that activate hormone-sensitive lipase
type of signaling

Answer 8

glucagon and epinephrine (mobilization of fatty acids from storage)
G protein coupled receptor signaling via cAMP/PKA

Question 9

Mobilization of fatty acids from storage pathway

Answer 9

1) Glucagon binds GPCR, G protein, adenylyl cyclase, cAMP
2) PKA active phosphorylates hormone sensitive lipase and perilipin proteins
3) PKA active also triggers dissociation of CGI from perilipin
4) CGI recruits adipose triacylglycerol lipase TAG–> DAG
5) Active hormone sensitive lipase gets access to lipid droplet surface converting DAG –> MAG
6) Monoacylglycerol lipase MAG –> free FA and glycerol
7) up to 10 FA bound by serum albumin in blood for transport

Question 10

Perilipin

Answer 10

protein that coats lipid droplets and makes them inaccessible and prevents mobilization of fatty acids

Question 11

CGI-58

Answer 11

comparative gene identification
58 specifically in adipose tissue

Question 12

Glycerol catabolic pathway

Answer 12

Phosphorylation: Glycerol –> Glycerol-3-phosphate
Enzyme: glycerol kinase (uses ATP)

Oxidation: Glycerol-3-phosphate –> dihydroxyacetone phosphate
Enzyme: glycerol-3-phosphate dehydrogenase (NOT GADPH)

Isomerization: dihydroxyacetone phosphate –> Glyceraldehyde-3-phosphate
Enzyme: triose phosphate isomerase
Continues on to glycolysis

Question 13

Activation of FAs for transport into mitochondria

Answer 13

12C FA and lower can just enter unassisted

14C FA and higher require acyl-CoA activated
Enzyme: fatty acyl-coA synthase
Location: mitochondria
ATP + Fatty acyl –> Fatty acyl-adenylate (enzyme bound) + 2Pi
Fatty acyl-adenylate + CoA-SH –> Fatty acyl CoA + AMP

Question 14

Fatty acyl-CoA can also be used to

Answer 14

synthesize longer membrane lipids

Question 15

in plants fatty acid beta oxidation occurs in

Answer 15

Peroxisomes

Question 16

carnitine acyltransferase I is inhibited by

Answer 16

malonyl coA (1st intermediate of FA synthesis)

Question 17

transport of FA into mitochondria

Answer 17

1) carnitine acyltransferase I replaces coA for carnitine on FA
2) complex enters mitochondrial matrix
3) carntine acyltransferase II replaces carnitine for CoA inside matrix
4) carnitine returns across mitochondria matrix in antiport with incoming acyl-carnitines

Question 18

beta oxidation of 16C saturated FA equation
enzymes in order and their products

Answer 18

ex. 1 palmitoyl-coA –> 8 Acetyl coA, 7 FADH2/7 NADH/7 H+ ( 28 ATP + 7 H2O)
1) acyl-coA dehydrogenase (FAD –> FADH2)
2) enoyl-CoA hydratase (H2O used)
3) beta-hydroxylacyl-CoA dehydrogenase (NAD+ –> NADH + H+)
4) acyl-coA acyltransferase / thiolase (CoA-SH used, produces Acetyl coA for CAC)

Question 19

equation to calculate products of beta oxidation

Answer 19

4C FA –> 2 Acetyl-CoA, 1 FADH2/NADH/H+, 4(1) ATP, 1 H2O

Question 20

Beta Oxidation enzymes in bacteria

Answer 20

Short chain FA: 4 enzymes unanchored

Long chain FAs: 3 enzymes (middle has activity of 2/3) anchored to mitochondrial membrane (matrix side)

Question 21

Beta oxidation of unsaturated FA

Answer 21

enoyl coA hydratase cannot act on unsaturated FA

Two additional enzymes required enoyl-coA isomerase (for mono and polyunsaturated FA) and enoyl-CoA reductase (for polyunsaturated FA only)

As a larger FA is catabolized, each round can require different enzymes

Question 22

example off 16C FA, 14C, 12C, 3C FA

Answer 22

16C: Palmitate acid
14C: Myristic acid
12C: Lauric acid
3C: Propionate

Question 23

Odd #C FA beta oxidation pathway

Answer 23

for an odd numbered C FA like propionyl-coA to form succinate to enter CAC

1) Propionyl-coA + biotin + HCO3 –> D-methylmalonyl-coA
propionyl-coA carboxylase

2) D-Methylmalonyl-coA –> L-methylmalonyl-coA
methylmalonyl-coA epimerase

3) L-methylmalonyl-coA + B12 –> succinyl-coA
methylmalonyl-coA mutase

Question 24

When does beta oxidation occur?

Answer 24

when there is need for energy (Low ATP activates AMPK leading to carnitine shuttle activation)
Carnitine shuttle is point of commitment

Question 25

What inhibits beta oxidation?

Answer 25

Malonyl-coA inhibits carnitine acetyltransferase I (b/c glucose is available)
High NADH inhibits beta-hydroxylacyl-coA dehydrogenase
High acetyl coA inhibits thiolase (acetyl-coA acyltransferase)

Question 26

what is AMPK?

Answer 26

AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is present in all mammalian cells
Beta oxidation enzyme regulator
Stimulates carnitine shuttle

Question 27

PPARg is

Answer 27

transcription factor that regulates beta oxidation enzymes

Question 28

Omega Oxidation pathway

Answer 28

Used for medium chain FA like 10C/12C

Location: ER
1) mixed-function oxidase
2) alcohol dehydrogenase
3) aldehyde dehydrogenase

Question 29

Omega Oxidation pathway

Answer 29

Used for medium chain FA like 10C/12C
Oxidation of FA from end farthest from carbonyl group
Forms double ended carbonyl ends from which acetyl coA can be produced in beta-oxidation

Location: ER in liver and kidney
1) mixed-function oxidase
2) alcohol dehydrogenase
3) aldehyde dehydrogenase

Question 30

types of ketone bodies
where they are produced
how to are used as energy

Answer 30

acetone, acetoacetate, beta-hydroxybutyrate
acetone produced in low concentrations
produced in the liver and transported to other tissues for conversion to acetyl coA
brain can adapt to use ketones for fuel during starvation

Question 31

ketone synthesis pathway

Answer 31

1) thiolase
2 acetyl coA –> acetoacetyl-coA
2) HMG coA synthase (liver cytosol)
acetoacetyl-coA –> HMG coA
3) HMG-coA lyase (liver mitochondria)
HMG-coA –> acetoacetate
4) beta-hydroxybutyrate hydrogenase
acetoacetate –> beta-hydroxybutyrate
OR
4) acetoacetate decarboxylase
acetoacetate –> acetone

Question 32

ketone catabolism pathway

Answer 32

liver cannot use ketone bodies as fuel lacking beta-ketoacyl coA transferase

1) betahydroxybutyrate dehydrogenase
betahydroxybutyrate –> acetoacetate
2) beta-ketoacyl coA transferase
acetoacetate –> acetoacetyl-coA
3) thiolase + CoA-SH
acetoacetyl-coA –> 2 acetyl-coA