Part 2 - lecture 3.3 - Exam

Question 1

Can TGs cross cell membranes?

Answer 1

No - they need to be hydrolyzed by lipoprotein lipase and hormone-sensitive lipase to release FAs and glycerol to other tissues

Question 2

Where does lipoprotein lipase work?

Answer 2

Hydrolyzes TGs in plasma lipoproteins and located of surface of enodthelial cells of capillarires and adjoining tissue cells

Question 3

Where does hormone sensitive lipase work?

Answer 3

Hydrolyzes TGs in adipose tissue to release products into plasma

Question 4

What happens when lipoprotein lipase hydrolyzes TGs?

Answer 4

Hydrolyzes FAs from 1 or 3 position of triglycerols in VLDL or chylomicrons – free FAs then bind to albumin or are taken up by tissue

Question 5

What happens when hormone sensitive lipase hydrolyzes TGs?

Answer 5

In adipose tissue Removes first FA from 1 or 3 position but controlled by cAMP
Epinephrine, glucagon and ACTH stimulate while insulin inhibits – released FAs bind to albumin and glycerol returns to liver

Question 6

What does utilization of FAs for energy production depend on?

Answer 6

Metabolic status of body and varies from tissue to tissue

Question 7

What type of tissues rely on utilization of FAs for energy production?

Answer 7

Cardiac and skeletal

Question 8

What brings on increase of FA utilization for energy?

Answer 8

Storage - also uses ketone bodies

Question 9

Where does beta oxidation of FAs occur?

Answer 9

Mitochondria

Question 10

How does beta oxidation of FAs occur?

Answer 10

Step by step removal of C2 AcCoA from carboxyl end of FA - dehydrogenation, hydration, oxidation, thiolysis – FADH2 and NADH produced at each step and AcCoA used in TCA – NADH and FADH2 used in terminal oxidation

Question 11

How much ATP/palmitate does beta oxidation of FAs give?

Answer 11

129 ATP

Question 12

What do FAs convert to in beta oxidation and how?

Answer 12

Fatty Acyl CoA by fatty acyl CoA synthase which is located on the outer mito membrane – uses 1 ATP

Question 13

What carries acyl groups across mito membrane?

Answer 13

Carnitine for C12-C18 chains - (shorter are independent) - on outer membrane acyl transferred by carnitine pamitoyltransferase I (CPT1) and on inner translocase moves acyl carnitine and through CPTII becomes acylCoA

Question 14

How are FAs activated to fatty acylCoA and where is the enzyme found?

Answer 14

Fatty acylCoA synthase on outer mito membrane

Question 15

How many ATP are used in beta oxidation?

Answer 15

2 - 1 at CPTI and 1 at CPTII steps

Question 16

What are the types of acyl-CoA dehydrogenases?

Answer 16

VLCAD, LCAD, MCAD, SCAD

Question 17

What do genetic defects of CoA dehydrogenases lead to?

Answer 17

Accumulation of FA in liver – hepatic mitochondrial damage and impaired liver function – metabolic derangements - can be detected in urine

Question 18

What happens in dehydrogenation in beta oxxidation?

Answer 18

Dehydrogenase removes H atoms to form enoyl CoA – trans double bond and FAD reduces – 2 ATP formed from each double bond formed

Question 19

What happens in hydration in beta oxidation?

Answer 19

With water and enoyl-CoA hydratase gives 3-L-Hydroxyacyl-CoA

Question 20

What happens during the second dehydrogenation of beta oxidation?

Answer 20

3-:-hydroxyacyl-CoA dehydrogenase gives beta-ketoacyl CoA and NADH which can yield 3 ATPs

Question 21

What happens in the last step of beta oxidation?

Answer 21

Cleavage of beta-ketoacyl-CoA to AcCoA and fatty acyl-CoA that is 2C shorter by thiolase

Question 22

What are the reverse enzymes for synthesis in beta oxidation?

Answer 22

Thioesterase – reductase instead of dehydrogenase and dehydratease instead of hydratase

Question 23

What regulates beta oxidation?

Answer 23

availability of substrates and cofactors and rate of processing acetyl CoA - CPTI inhibited by Malonyl CoA

Question 24

What is the rate limiting step of beta oxidation?

Answer 24

Transport of FAs to the mitochondria by carnitine shuttle system

Question 25

How many ATPs are generated by one palmitate after beta oxidation and TCA, etc.?

Answer 25

129 ATP

Question 26

What happens to odd chain FAs for oxidation?

Answer 26

Converted to propionyl CoA --(biotin)--> methylmalonyl CoA --mutase(VB12)--> succinyl CoA for TCA

Question 27

What happens to unsaturated FA oxidation?

Answer 27

Need isomerase to change cis to trans formation for hydratase enzyme - if polyunsaturated then an additional NADPH-dependent reductase is needed

Question 28

What goes through oxidation in peroxisomes and how?

Answer 28

Very long chain FA (C20 or more) use dehydrogenase to produce FADH2 which is oxidized by O2 to H2O2 which catalase uses to reduce to water

Question 29

What is zellweger syndrome?

Answer 29

Genetic defect in peroxisomal assembly in all tissues -- leads to accumulation of VLCFA

Question 30

What is adrenoleukodystrophy?

Answer 30

A genetic x linked defect in peroxisomal oxidation -- leads to accumulation of VLCFA

Question 31

Where does beta oxidation of branched-chain FAs stop?

Answer 31

At the methyl branch and additional enzymes are needed

Question 32

What is Refsume disease?

Answer 32

A rare deficiency in extra enzymes needed for branched chain FA -- causing nerological symptoms due to phytanic acid build up

Question 33

Where does alpha-oxidation of FA occur and what enzymes are used and what does it produce?

Answer 33

ER and mitochondria, monooxygenase enzymes with cytochrome P450, NADPH, oxygen and produces hydroxylated FAs

Question 34

Where does omega-oxidation of FAs occur and what is produced?

Answer 34

ER, enzymes produce dicarboxylic acids

Question 35

What makes up ketone bodies? and what are they important fr?

Answer 35

Acetoacetic acid and beta-hydroxybutyric acid - important for CNS -- water-soluble forms of lipid-based energy

Question 36

What is the primary site for ketone synthesis?

Answer 36

Liver, some in kidney -- in mitochondrial matrix

Question 37

How does ketone synthesis occur?

Answer 37

2 AcCoA condense by beta-ketothiolase to give acetoacyl CoA which condenses with another AcCoA to give beta-hydroxymethylglutaryl COA (HMGCoA) --> cleaved by HMGCoA lyase to give acetyl CoA and acetoacetic acid `

Question 38

What is acetoacetate from ketone synthesis converted into?

Answer 38

A fraction reduced to D-beta-hydroxybutyrate and acetone by decarboxylation

Question 39

Where else can HMGCoA be made?

Answer 39

In cytosol of liver but lyase is absent and HMGCoA is instead used for cholesterol synthesis

Question 40

How are ketone bodies utilized?

Answer 40

Used by cardiac and skeletal muscle and the CNS, when starvation is induced or when their is an insulin deficiency ketone bodies replace glucose as a major fuel source

Question 41

What must be formed for keton bodies to be used by non-hepatic tissues?

Answer 41

Acetoacetyl CoA by acetoacetate-succinyl CoA transferase which is is present in most-non hepatic tissues but not liver

Question 42

What are the roles of insulin and glucagon in AcCoA ketone formation?

Answer 42

Insulin stimulates glycolysis which generates AcCoA for energy and FA and cholesterol Glucagon stimulates AA and FAs to give energy and ketone bodies