fatty acid oxidation

Question 1

number of carbons for:

short, medium, long, very long chain FA

Answer 1

short= 2-4
medium= 6-12
long= 14-20
very long= over 22

Question 2

C present in most dietary and stored fats

Answer 2

16, 18

Question 3

major pathway for b-oxidation occurs in the-

Answer 3

mitochondria

Question 4

when is b-oxidation in the peroxisome needed?

Answer 4

b-oxidation in the peroxisome is an intermediate step that is needed for very long chain FA (22+ Carbons); this process will break FA into Medium chain length and then FA will enter mitochondria for completion

Question 5

in b-oxidation, how are FA transported into the cell?

Answer 5

via fatty acid binding proteins

Question 6

in b-oxidation, where/how are FA activated

Answer 6

in cytoplasm, acyl-CoA syntheses add CoA to activate FA using ATP

Question 7

what is the location of acyl-CoA syntheses? why are there many isoforms?

Answer 7

located on the ER and outer mito membranes

many isoforms bc each is specific for one FA length

Question 8

what FA use the carnitine shuttle?

Answer 8

Long chain

medium chain do not require

Question 9

3 steps in the carnitine shuttle

Answer 9

1-CPT1 on outer mito membrane facing cytosol, transfers FA from CoA to OH of carnitine (forming acylcarnitine) and moving into inner membrane space
2- antiporter on the inner mito membrane mediates exchange of carnitine for acylcarnitine, now acylcarnitine in mito matrix
3- CPT2 in mito matrix transfers FA from carnitine back to CoA

Question 10

what is the main control mechanism of FA oxidation? how?

Answer 10

carnitine shuttle

through regulation by malonyl-CoA

Question 11

what forms malonyl-CoA? why is it formed?

Answer 11

malonyl-CoA is formed from acetyl-coA using acetyl-CoA carboxylase, in response to high acetyl-CoA

Question 12

how does malonyl-CoA inhibit the carnitine shuttle?

Answer 12

malonyl-CoA inhibits CPT1

Question 13

what is the end product of b-oxidation?

Answer 13

acetyl-CoA

Question 14

what are the fates (3) of acetyl-CoA derived from b-oxidation?

Answer 14

in fed state- acetyl-CoA is oxidized in TCA cycle
in fasted state- acetyl-CoA is used to make ketone bodies in liver, in peripheral tissues ketone bodies are converted back to acetyl-CoA and are used for TCA cycle/energy

Question 15

4 enzymes used in b-oxidation

Answer 15

1- acyl-CoA dehydrogenase
2- enoyl-CoA hydratase
3- b-hydroxyacyl-CoA dehydrogenase
4- acyl-coA acetyltransferase

Question 16

describe the action of acyl-CoA dehydrogenase

Answer 16

makes C=C between a and B carbons, uses FAD+

Question 17

describe the action of enoyl-CoA hydralase

Answer 17

adds H2O to add OH to B carbon

Question 18

describe the action of b-hydroxyacyl-CoA dehydrogenase

Answer 18

removes H from OH on B carbon, to make C=O, uses NAD+

Question 19

describe the action of acyl-CoA acetyl transferase

Answer 19

adds CoASH to make acyl-CoA + acetyl-CoA

Question 20

what is unique about the acyl-coA dehydrogenase that is used for very long chain FA?

Answer 20

it is bound to the inner mito membrane, all others are soluble in mito matrix

Question 21

what is contained in the “trifunctional protein complex”?

Answer 21

enoyl-CoA hydralase, b-hydroxyacyl-CoA dehydrogenase and acyl-CoA acetyltransferase for long chain FA; those for shorter chain FA are soluble in matrix

Question 22

how many ATP are used in the activation process of FA?

Answer 22

2, one in the cytosol and 1 inside the mitochondria

Question 23

describe regulation of b-oxidation by malonyl-coA

Answer 23

malonyl-CoA will decrease b-oxidation; malonyl-CoA is synthesized by acetyl-CoA carboxylase when acetyl-CoA levels are high, malonyl-CoA inhibits CPT1 and thereby decreases b-oxidation

Question 24

describe regulation of b-oxidation by insulin

Answer 24

insulin promotes FA synthesis by promoting the activity of acetyl-CoA carboxylase. Increased acetyl-CoA carboxylase activity will cause increased levels of malonyl-CoA that will inhibit CPT1 and decrease b-oxidation

Question 25

describe regulation of b-oxidation by energy charge

Answer 25

when ATP levels are high, ETC will slow. this will decrease the availability of NAD+ and thereby slows b-oxidation

Question 26

what is the main source of odd chain FA?

Answer 26

dietary in milk, comes from cow flora's production of propionate that becomes incorporated into milk fats

Question 27

what is the result of b-oxidation of an odd chain FA?

Answer 27

final reaction will yield 1 acetyl-CoA and 1 propionyl-CoA

Question 28

what will happen to proprionyl-CoA after b-oxidation is complete?

Answer 28

in the liver, propionyl-CoA will be converted to succinyl-CoA that is then converted to oxaloacetate by the TCA cycle. Resulting oxaloacetate is then used for gluconeogenesis

Question 29

what is unique about b-oxidation of very long chain FA?

Answer 29

Very long chain (22+) must be converted to medium or short chain FA in peroxisomes before it can enter the mitochondria

Question 30

what do peroxisomes use for FA transport?

Answer 30

import- ABC transporters | export- carnitine shuttle

Question 31

what is unique about oxidation in perxisomes?

Answer 31

less energy is harnessed because FAD+ is used to form H2O2 (then broken down by catalase), NADH is generated and transferred to mitochondria, no ATP is directly made. Overall is less energentially favorable

Question 32

zellweger syndrome

Answer 32

lack of functional peroxisomes that causes an accumulation of FA C24-32

Question 33

X-linked adrenoleukodystrophy

Answer 33

specific defect in peroxisomal oxidation of VLCFA leading to their accumulation

Question 34

what is the purpose of a-oxidation?

Answer 34

for branched-chain FA-used when there is a methyl group present on the b-carbon, a-oxidation will remove the methyl group so that the compound can undergo b-oxidation

Question 35

where is a-oxidation?

Answer 35

in peroxisomes

Question 36

what is a common reaction that requires a-oxidation?

Answer 36

chlorophyll --> phytanic acid

Question 37

refsum disease

Answer 37

defective a-oxidation leads to accumulation of branched chain FA in the CNS, neurologic sx appear first

Question 38

what is the action of w-oxidation?

Answer 38

w-oxidation is a detox pathway that oxidizes the w-carbon to form a dicarboxylic acid that is more soluble and can be excreted

Question 39

what class of enzymes commonly use w-oxidation?

Answer 39

cytochrome P450

Question 40

medium chain acyl-CoA dehydrogenase deficiency

Answer 40

medium chain FA accumulate, will be converted to dicarboxylic acids by w-oxidation and excreted; m/c genetic disease related to FA catabolism, fasting and exercise will cause hypoketotic hypoglycemia

Question 41

2 types of ketone bodies

Answer 41

acetoacetate and b-hydroxybutarate

Question 42

what is the main ketone body in blood?

Answer 42

b-hydroxybutarate

Question 43

what enzyme is used to convert between the 2 types of ketone bodies?

Answer 43

b-hydroxybutarate dehydrogenase

Question 44

after how many days of fasting will ketone body levels plateau?

Answer 44

20

Question 45

what triggers the formation of ketone bodies?

Answer 45

during fasting, oxaloacetate is used up by gluconeogenesis and thus TCA cycle slows leading to accumulation of acetyl-CoA; acetyl-CoA present in liver mitochondria is used to make ketone bodies

Question 46

how are ketone bodies used for energy? (3)

Answer 46

b-hydroxybutarate --> acetoacetate --> acetoacyl-CoA --> 2 acetyl-CoAs

Question 47

what are the enzymes used for ketone body degradation?

Answer 47

1- b-hydroxybutarate dehydrogenase 2- succinyl-CoA/acetoacetate-CoA transferase 3- thiolase

Question 48

how does acetone form?

Answer 48

spontaneous decarboxylation of acetoacetate will form acetone

Question 49

why are children more prone to ketosis? (3)

Answer 49

- use more energy per Kg mass - high higher brain to liver ratio - deplete glycogen stores more rapidly

Question 50

what is the m/c cause of ketosis in children?

Answer 50

infections that cause anorexia/vomiting

Question 51

what is the basis of a ketogenic diet?

Answer 51

3:1 lipid to carbohydrate calories

Question 52

2 diseases that can be helped with ketogenic diet

Answer 52

epilepsy (dec seziures) | pyruvate dehydrogenase def

Question 53

why are medium chain FA "more ketogenic"?

Answer 53

MCFA are more likely to be oxidized vs. stored OR be incorporated into membranes (overall- more likely to be used and not stored)

Question 54

hypoglycemia in the absence of increased ketone body formation suggests-

Answer 54

disease of FA transport/oxidation

Question 55

systemic carnitine deficiency

Answer 55

decreased carnitine will decrease carnitine shuttle and cause impaired use of long chain FA. deficiency is caused by defect in OCTN-2 leading to impaired reabsorption of carnitine from the kiddy and impaired accumulation of carnitine in mm, treat with carnitine and high carb/low fat diet