Fatty Acid Oxidation & Ketone Body Metabolism

Question 1

what mobilizes fatty acids?

Answer 1

hormone sensitive lipase

Question 2

what activates hormone sensitive lipase?

Answer 2

glucagon and epinephrine

Question 3

where does oxidation of fatty acids occur?

Answer 3

matrix of the mitochondria

Question 4

what is carnitine synthesized by in the liver?

Answer 4

lysine and methionine

Question 5

What does each round of beta-oxidation produce?

Answer 5

a NADH+H+, a FADH2, and acetyl coA

Question 6

Where does oxidation occur?

Answer 6

between the alpha and beta carbon

Question 7

to break a Nchain fatty acid, how many spirals is it?

Answer 7

(N/2)-1

Question 8

how many spirals does each ATP use?

Answer 8

5

Question 9

what does the final spiral of B-oxidation of odd-chain length fatty acids yield?

Answer 9

propionyl CoA

Question 10

a deficiency of B12 leads to what?

Answer 10

increased levels of methylmalonyl CoA

Question 11

what is a negative allosteric modulator of carnitine palmitoyl transferase I?

Answer 11

malonyl coA

Question 12

in a well fed state, what does insulin do

Answer 12

it keeps acetyl coA carboxylase active and increases malonyl coA

Question 13

during fasting and starvation, what does glucagon do?

Answer 13

it causes lipoylsis and increases fatty acids which inhibits acetyl coA carboxylase

Question 14

(1) autosomal recessive
(2) impairs oxidation of medium chain fatty acids (C8-C12)
(3) accumulation of medium chain fatty acids and esters in tissues
(4) spillover of C8-C12 acylcarnitine species in blood
(5) hypoglycemia during fasting due to lack of ATPs
(6) decreased gluconeogenesis and ketone body formation
(7) non-ketotic hypoglycemia and block in hepatic beta-oxidation
(8) lethargy, coma, and death if untreated
(9) treated by IV glucose, prevented with frequent feeding, high carb, low fat diet

Answer 14

MCAD Deficiency

Question 15

(1) inherited (autosomal recessive) or acquired
(2) mutation in genes for Carnitine Palmitoyl Transferase I or II
(3) low protein diet, impaired synthesis of carnitine in liver disease, loss of carnitine during hemodialysis process
(4) decreased LCFA metabolism leads to accumulation of LCFAs in tissues and wasting of acyl-carnitine in urine
(5) Symptoms: cardiomyopathy, skeletal muscle myopathy, encephalopathy, impaired liver function, muscle ache and weakness, rhabdomyolysis and myoglobinuria upon exercise
(6) treated with IV glucose and cease of muscle activity

Answer 15

Carnitine Deficiency

Question 16

(1) autosomal recessive
(2) mutation in PEX genes encoding for peroxins
(3) accumulation of VLCFAs and BCFAs that are normally degraded in peroxisomes
(4) Symptoms: liver and kidney dysfunction, hepatomegaly, high levels of copper and iron in blood, severe neurologic defects, hypomyelination, craniofacial and skeletal malformations

Answer 16

Zellweger Syndrome

Question 17

(1) autosomal recessive
(2) deficiency of peroxisomal phytanic acidhydroxylase
(3) impaired-oxidation of phytanic acid
(4) buildup of phytanic acid and derivatives in plasma and tissues
(5) cerebellar ataxia, retinitis pigmentosa, chronic polyneuropathy
(6) treated with low-phytanic acid diet

Answer 17

Refsum Disease

Question 18

(1) caused by ingestion of unripe Ackee fruit which contains hypoglycin A
(2) hypoglycin A is metabolized to methylenecyclopropylacetic acid (MCPA)
(3) MCPA interferes with transport of LCFAs into mitochondria and inhibits acyl-CoA dehydrogenases involved in beta-oxidation
(4) decrease in ATPs and gluconeogenesis
(5) severe vomiting 2-6 hours after ingestion, severe hypoglycemia, convulsions, coma, death

Answer 18

Jamaican Vomiting Sickness

Question 19

when does ketone body synthesis occur?

Answer 19

during periods of starvation and low insulin levels

Question 20

Which ketone body is volatile?

Answer 20

acetone

Question 21

Which ketone bodies are water soluble?

Answer 21

acetoacetate and beta-hydroxybutyrate

Question 22

(1) low insulin/glucagon ratio stimulates excess beta-oxidation depleting NAD+ and saturating TCA cycle with acetyl CoA shunting acetyl CoA toward ketone body formation
(2) acetoacetic acid and 3-hydroxybutyric acid (ketone bodies) accumulate in blood and decrease pH
(3) acetone is volatile and hence exhaled giving fruit odor to breath

Answer 22

Diabetic Ketoacidosis

Question 23

What does Active hormone sensitive lipase do?

Answer 23

It breaks triacylglycerol to di- and mono- acylglycerol, releasing FAs

Question 24

What does monoacylglycerol lipase do?

Answer 24

it acts on monoalcylglycerol to release FAs and glycerol

Question 25

What activates fatty acid by adding CoA?

Answer 25

Acyl CoA synthetase