Degradation of Fatty Acids and B-Oxidation

Question 1

How does acetyl CoA feed the KB synthesis instead of entering TCA

Answer 1

When NADH/NAD is high then malate –> OAA is reversed. Acetyl CoA can not enter the TCA

Question 2

B ox of unsaturated fa

Answer 2

Dietary unsaturated fatty acids contain cis double bonds. Cis-double bonds cannot be processed by the β oxidation machinery. β oxidation proceeds until the cis bond is reached. The cis bond is isomerized to trans bond and β oxidation can proceed further

Question 3

The main diff of peroxisomal degradation from mitochondrial B oxidation

Answer 3

No FAD(2H) production in peroxisomes- instead H2O2 is produced

Question 4

Regulation of B oxidation Insert pic

Answer 4

High I/g (during fed) stimulates acetylCoA carboxylase - then malony CoA inhibits CPTI (IN THE LIVER)

Question 5

allostric inhibitor of CPTI

Answer 5

malonyl CoA (formed from acetyl Coa by acetyl CoA carboxylase)

Question 6

fa activation

Answer 6

In order to be metabolized, fatty acids must be converted to fatty acyl CoA

Question 7

Tx or deficiency of carnitine metabolism

Answer 7

H. Carb, L fat diet: rich in medium chain length fa

Question 8

Hypoketotic diseases

Answer 8

Deficiencies in carnitine metabolism Deficiencies in β-oxidation (such as MCAD) Both cause hypoketotic hypoglycemia

Question 9

sources of fa during fed state

Answer 9

chylomicrons and VLDLs VLDLs are made by liver

Question 10

Intercellular localization of fa

Answer 10

Mitochondria Main site of b-oxidation Degradation of long, medium and short chain fatty acids Peroxisomes- very long and branched chain SER omega-oxidation in dicarboxylic acid

Question 11

MCAD deficiency

Answer 11

Hypoketotic hypoglycemia Elevated C6-C10 acylcarnitine levels in plasma and urine. Elevated C6-C10 dicarboxylic acids in urine (due to ω oxidation). (adipic and subaric acids are most diagnostic in urine). Similar onset (fasting, infection) and symptoms as in carnitine deficiency. Responsible for some of the sudden death during infancy. Treatment with glucose and carbohydrate rich diet.

Question 12

Transport of long chain fatty acids into mitochondria

Answer 12

carnitine-conjugated (longer than 12C) smaller than 12C carnitine is not required.

Question 13

Oxidation of medium chain fatty acids

Answer 13

Dietary medium chain fatty acids are not stored in triglycerides in the human body They do not need to form fatty acyl CoA or carnitine conjugates to enter mitochondria Once they are in the mitochondria, they are conjugated with CoA. Some medium chain fatty acids are produced in the peroxisome from very long chain fatty acids, conjugated to carnitine and then transported into mitochondria. β oxidation then proceeds similarly to the long chain fatty acids.

Question 14

carnitine storage

Answer 14

skeletal muscle

Question 15

carnitine

Answer 15

Synthesized from protein-bound lysine. Synthesis requires S-adenosyl-methionine (SAM) as methyl donor. Synthesis starts in skeletal muscle and completed in liver and kidney. Most carnitine is stored in skeletal muscle in the human body. Transported into cells by specific carnitine transporter. Carnitine can be used as a dietary supplement to accelerate fatty acid oxidation.

Question 16

w oxidaiton

Answer 16

Takes place in the smooth ER. Produces dicarboxylic acids. The dicarboxylic acids can undergo mitochondrial β oxidation. Normally, a minor process. Increases if β oxidation is deficient (see MCAD deficiency previously)

Question 17

deficiency of carnitine metabolism

Answer 17

Consequences of failure to degrade long chain fatty acids - during fasting or infection -leads to hypoketotic hypoglycemia during fasting -elevated liver enzymes and ammonia lipid droplet accumulation in: liver hear Sk. m.

Question 18

site of omega oxidation of fatty acids into dicarboxylic acids

Answer 18

SER

Question 19

CPTII deficiency

Answer 19

Plasma acylcarnitine- high Plasma free carnitine-low urine free carnitine- normal

Question 20

because of missing this enzyme, the liver can not produce acetyl Co A from KB

Answer 20

Succinyl CoA- acetoacetate transferase

Question 21

MCAD deficiency treatment

Answer 21

glucose and carb rich diet

Question 22

enzyme deficiencies that cause organic acidemias (priopionic or methyl malonyl acidemia)

Answer 22

enzyme defeciencies in the propionyl CoA degradation.

Question 23

CAC deficiency

Answer 23

Plasma acylcarnitine- high Plasma free carnitine-low urine free carnitine- low

Question 24

blood transport of fa

Answer 24

In fed state, dietary fatty acids are transported as triglycerides inside lipoprotein particles (chylomicrons). In fed state, fatty acids synthesized in the liver from glucose are transported as triglycerides inside lipoprotein particles (VLDLs). Fatty acids released from the adipose tissue (during fasting or exercise) are bound to albumin and delivered to target tissues.

Question 25

CPTIA deficiency (liver)

Answer 25

Plasma acylcarnitine- Low Plasma free carnitine-High urine free carnitine- Low

Question 26

Two conditions with high acylplasma carnitine, and normal urine free carnitine

Answer 26

CPTII and CAC deficiency

Question 27

Primary carnitine deficiency (transport into the cell)

Answer 27

Plasma acylcarnitine- low Plasma free carnitine-low urine free carnitine-elevated

Question 28

Condition under which w-oxidation increases

Answer 28

When B oxidation is deficient

Question 29

sources of fa during fasting or exercise

Answer 29

Triglycerides are degraded in the adipose tissue into fatty acids and glycerol by hormone sensitive lipase. The process is stimulated by elevated glucagon/insulin ratio and high epinephrine levels.

Question 30

Oxidation of odd fatty acids

Answer 30

The last cycle of β oxidation produces 1 acetyl CoA (2 carbon) and 1 propionyl CoA (3 carbon). Propionyl CoA is degraded to succinyl CoA which enters the TCA cycle. Enzyme deficiencies in the propionyl CoA degradation pathway cause organic acidemias (propionic or methyl-malonyl acidemia).

Question 31

Ketoacidosis

Answer 31

elevated KB in blood Type I diabetes – (lack of insulin, high glucagon/insulin ratio) adipose and liver “thinks” the body is fasting Acute consumption of large amounts of alcohol: Alcohol metabolism increases NADH, the malate–OAA reaction is reversed, acetyl-CoA is used for ketone body synthesis

Question 32

There are only few tissues/cells that do not use fatty acids during fasting as energy source

Answer 32

RBC Brain-most fa cant pass through