Lipid Metabolism and Catabolism Ketone Body Synthesis and Utilization Flashcards Preview

Biochemistry Post Midterm > Lipid Metabolism and Catabolism Ketone Body Synthesis and Utilization > Flashcards

Flashcards in Lipid Metabolism and Catabolism Ketone Body Synthesis and Utilization Deck (66):
1

why can't glycerol formed in the adipose tissue not be reused in the adipose tissue?

adipose tissue lacks glycerokinase

2

what does glycerol enter once it it enters the liver?

glycolysis
gluconeogenesis
TAG synthesis

3

What is the storage form of lipid?

TAG

4

where and how is TAG stored?

white adipose tissue as lipid droplets

5

when are fatty acids in the TAG released as free fatty acids?

energy deficient state - FASTING

6

What enzyme breaks down TAGS?

hormone sensitive (HS) lipase

7

which state is HS lipase active? What activates it?

phosphorylated state
low insulin/glucagon ratio
fasting, flight, fight
- epinephrine stimulated via cAMP

8

what are the free fatty acids from adipose tissue bound to in blood?

albumin

9

which is NOT an important fuel source for the brain during starvation?

free fatty acids (not oxidized for energy by the brain)

10

what is beta oxidation?

oxidation of fatty acids at the beta carbon of the fatty acid

11

where does beta oxidation take place?

mitochondria

12

What are the stages of beta oxidation?

activation of fatty acid (cytosol)
transport of fatty acid from the cytosol to mitochondria
beta oxidation proper (reactions of beta oxidation)

13

what inhibits CPT-i?

malonyl CoA (when fatty acid synthesis is active, beta oxidation is inhibited)

14

what does one sequence of reactions of beta oxidation result in?

the cleavage of 2 C atoms (removed as acetyl CoA)

15

where are fatty acids used for beta oxidation and energy metabolism especially?

heart
skeletal muscle
liver

16

what fatty acids pass BBB to give energy to brain?

omega 3 and 6 only! - free fatty acids cannot pass

17

how are fatty acids activated? What is formed?

fatty acyl CoA synthetase (thiokinase)
forms fatty acyl CoA

18

whats the purpose of the carnitine shuttle?

transport long chain (16 - 20 C) fatty acyl groups into the mitochondria for beta oxidation

19

do medium chain fatty acids need a shuttle?

no, they enter directly into the mitochondrial matrix where they are activated to medium chain fatty acyl CoA for beta oxidation

20

where is CPT-I found? What are its substrates? What is the product?

outer mitochondrial membrane
fatty acyl CoA and free carnitine
forms fatty acyl carnitine

21

when is the carnitine shuttle activated?

when there is increased availability of cytosolic fatty acids during fasting

22

when fatty acid synthesis is taking place, what is inhibited?

carnitine shuttle

23

what inhibits CPT-I?

malonyl-CoA

24

when is malonyl-CoA formed?

in liver cytosol during fatty acid synthesis

25

what is deficiency of CPT-I due to? What are the symptoms?

rare, due to deficiency of the isozyme found in the liver
leads to severe hypoglycemia and hypoketonemia

26

What is deficiency of CPT-II due to? What are the symptoms?

affects the isozyme of the muscles
leads to cardiomyopathy and muscle weakness

27

what happens to TAGs in CPT-II deficiency?

TAGS accumulate in skeletal muscle and prolonged exercise leads to myoglobinuria and elevated levels of CK-MM in blood

28

where are the enzymes for beta oxidation present?

mitochondrial matrix

29

what does a cell need in order to perform beta oxidation?

mitochondria and an active ETC and OP which reforms NAD+ and FAD needed as coenzymes for Beta oxidation

30

oxygen deficiency leads to high levels of NADH, which does what?

inhibits beta oxidation
inhibits PDH and TCA cycle

31

what does each spiral of Beta oxidation produce?

1 FADH2
1 NADH
1 acetyl CoA
1 fatty acyl CoA that is 2 C shorter

32

how many equivalents of ATP are produced in beta oxidation?

5 ATP

33

what does 1 round of the TCA cycle produce?

3 NADH
1 FADH2
1 GTP

34

how many ATP equivalents are produced in 1 round of TCA?

12 ATP

35

why is it significant that beta oxidation only cleaves 2 C from the fatty acyl CoA?

leaves a shorter fatty acyl CoA that can continue in more beta oxidation spirals

36

how many ATP does the total degradation of palmitate generate?

129 ATP

37

how many ATP are formed when glucose is subjected to aerobic glycolysis, PDH and TCA cycle?

38 ATP (using malate -aspartate shuttle)

38

what does odd chain fatty acids produce in beta oxidation?

acetyl CoA
and
the last acyl CoA = propionyl CoA

39

What is the significance of propionyl CoA?

only part of the fatty acid that can provide carbons for gluconeogenesis

40

what does propionyl CoA carboxylase need as a cofactor?

biotin

41

what does methylmalonyl CoA mutase need as a cofactor>

Vitamin B12

42

what accumulates as a result of Refsum disease?

phytanate

43

what is deficient in Refsum Disease?

deficiency of the peroxisomal phytanyl CoA alpha - hydroylase = defect in alpha oxidation

44

what are the symptoms of Refsum disease?

visual defects
ataxia
polyneuropathy
skeletal manifestations

45

is there a Tx for Refsum disease? What is it?

Yes, dietary restriction of branched chain fatty acids

46

what is MCAD deficiency?

most common inherited autosomal recessive enzyme deficiency
decreased ability to oxidize fatty acids with 6-10C (medium chain)

47

what are the symptoms of MCAD deficiency?

on fasting, the liver and muscles are not able to use fatty acids as an energy source
profound hypoglycemia!

48

what are excreted in urine with MCAD deficiency?

medium chain acyl carnitines
dicarboxylic acids
presence of CK-MM and myoglobin in urine = skeletal muscle damage

49

what leads to the inhibition of MCAD by hypoglycin A?


unripe ackee fruit - ONLY unripe!
Jamaican vomiting sickness

50

what does Jamaican vomiting sickness inhibit and result in?

inhibits beta oxidation
results in profound hypoglycemia

51

how much energy supply is from fatty acid oxidation on an overnight fast?

60-70%

52

what are common features of systemic fatty acids oxidation disorders? (MCAD, carnitine deficiency, CPT deficiency)

hypoglycemia
hypoketosis

53

what accumulates in Zellweger syndrome and why?

very long chain fatty acids accumulate
cannot be degraded because lack of peroxisomes

54

what are the clinical manefestations of Zellweger syndrome?

neurological manifestations (mental retardation)
hepatomegaly
fatal in infancy!

55

how is ketone bodies in liver made?

acetyl CoA from fatty acid oxidation are converted to ketone bodies - peripheral tissues cannot synthesize ketone bodies

56

what are the three ketone bodies?

acetoacetate
3-hydroxybutyrate (beta hydroxybutyrate)
acetone

57

which ketone bodies are transported to peripheral tissues? What happens to them there?

acetoacetate and 3-hydroxybutyrate

reconverted to acetyl CoA - that are oxidized by TCA cycle!

58

what organ synthesizes ketone bodies? why?

liver
contains lots of mitochondrial HMG CoA synthase

59

what is exhaled and smelt on breath of DM type I patients?

acetone

60

when does the liver synthesize ketone bodies?

during fasting, fight or flight situations

61

where does ketogenesis take place?

mitochondria

62

when is 3-hydroxybutyrate formed?

when ratio of NADH / NAd+ is increased - when Beta oxidation is predominant

63

what does the brain use in addition to glucose during prolonged starvation?

ketone bodies

64

What is the 'protein sparing effect of ketone bodies'?

Ketonebodies can be used by the brain during fasting –this adaptation spares the breakdown of muscle protein (amino acids) for gluconeogenesis

65

what does the brain use in addition to glucose during prolonged starvation?

ketone bodies

66

What is the 'protein sparing effect of ketone bodies'?

Ketonebodies can be used by the brain during fasting –this adaptation spares the breakdown of muscle protein (amino acids) for gluconeogenesis