Fatty Acid Metabolism / Ketone Bodies / lipid transport Flashcards Preview

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Flashcards in Fatty Acid Metabolism / Ketone Bodies / lipid transport Deck (82)
1

Long-chain fatty degradation requires

Carnitine dependent transport into mitochondrial matric

1

Inhibitor of carnitine acytransferase

Malonyl-coa

2

Steps of long chain degradation (and location

1. Fatty acid + coa --> Fatty acyl - coa (fatty acid coa synthase) (cytoplasm)
2. Carnitine dependent transportof Fatty acyl - coa into mitochondria
3. β-oxidation --> Fatty acyl - coa --> Acetyl coa (Acyl CoA dehydrogenase)
4. Acetyl coa --> Ketone bodies and TCA cycle

4

Systemic 1ry Carnitine deficiency - symptoms

1. Weakness
2. Hypotonia
3. Hypoketotic hypoglycemia

4

Acyl-coa dehydrogenase

Initial enzyme for β-oxidation
FAD to FADH2

5

Systemic 1ry Carnitine deficiency - pathophysiology

Inherited defect in transport of long chain fatty acids into the mitochondria --> toxic accumulation

7

Medium-chain acyl-coa dehydrogenase deficiency - pathophysiology / mode of inheritance / presentation

AR disorder of fatty acid oxidation --> decreased ability to break down fatty acids into acetyl coa --> accumulation of 8- to 10 - carbon fatty acyl carnites and hypoketotic hypoglycemia
may present in infancy or early childhood with vomiting, lethargy, coma + liver dysfunction --> can leat to sudden death

8

Mechanism of hypoglycemia in acyl-coa dehydrogenase deficiency

Acetyl coa is an +allosteric regulator of pyruvate carboxylase

8

Ketogenesis fuel and purpose (and location)

N the liver, fatty acids and amino acids are metabolyized to acetoacetate and β hydroxybutyrate (to be used in muscle and brain)

10

Ketogenesis fuel and purpose (and location)

In the liver, fatty acids and amino acids are metabolyized to acetoacetate and β hydroxybutyrate (to be used in muscle and brain)

11

Breath with ketones

Smells loke acetone (fruity odor)

12

types of ketone bodies (and urine test)

types: acetoacetate and β hydroxybutyrate
Urine test does not detect β hydroxybutyrate

12

Ketogenesis in alcoholism

Excess NADH shunts oxaloacetate to malate . Buildup of acetyl coa which shunts glucose and FFA toward the production of ketone bodies

13

3 main situations of ketogenesis (why)

1. Prolonged starvation (depletion of oxaloacetate for gluconeogenesis)
2. Diabetic ketoacidosis (depletion of oxaloacetate for gluconeogenesis)
3. Alcoholism (excess NADH shunts oxaloacetate to malate
--> buildup of acetyl-coa

14

Ketogenesis in prolonged starvation and diabetic ketogenesis

Oxaloacetate is depleted for gluconeogenesis. Buildup of acetyl coa which shunts glucose and FFA toward the production of ketone bodies

16

Ketogenesis in the liver - steps and metabolism

FA, aminoacids --> Acetyl-Coa --> HMG-CoA (HMG-CoA synthase) --> Autoacetate --> β-Hydroxybutyrate --> acetone (blood) --> expired by lungs
at extra hepatic tissue: β-Hydroxybutyrat --> acetoacetate --> Acetoacetyl-Coa (through TCA) --> Acetyl - Coa --> TCA

17

1g carbohydrate, 1g fat, 1g protein

fat --> 4 kca, carbohydrate --> 4 kca, alcohol --> 9Kcal

17

Metabolic priorities for fasting and starvation

Supply sufficient glucose to the brain and RBC and to preserve protein

18

energy source at exercise (time)

Ovreal performance: 0-1min declining and after plateau (peak at 0)
ATP: 0-2 sec (peak at 0)
Creatine phosphate: 0-10 sec (peak at 2)
aerobic metabolism: O-... (peak at 50 sec and then plateau)
Anaerobic metabolism: 0-1mon (peak at 25 sec)

20

Fed state (after a meal regulation) mechanism / regulation

Glycolysis and aerobic respiration
Insulin stimulates storage of lipids, proteins, glycogen

21

Fasting state (between meals) mechanism / regulation

Major: hepatic glycogenolysis
Minor: hepatic gluconeogenesis, adipose release of FFA
Glucagon, adrenaline stimulate use of fuel reserve

22

Fasting state (between meals) mechanism is regulated by

Glucagon, adrenaline stimulate use of fuel reserve

22

Glycogen serve depleted after how long

1 day

23

RBC cannot use ketones because

They lack mitochondria

24

Starvation after 3 days

Adipose stores (ketone bodies become the main source)
After these are depleted, vital protein degration leading to organ faillure and death

25

Starvation day 1-3 Blood glucose maintained by

1. hepatic gluconeogenesis
2. Adipose relase of FFA
3. Muscle and liver, which shift fuel use from glucose to FFA
4. Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl coa (from odd-chain FFA)

26

What does determine survival time at starvation

Amount of excess stores

27

Cholesterol synthesis rate limiting step is catalyzed by

HMG-CoA reductase

28

HMG-CoA reductase reaction

HMG-CoA to mevalonate

29

HMG-CoA regulation

Insulin+
Thyroxine +
Cholesterol -
Glucagon -

30

LCAT

lecithin cholesterol acyltransferase

31

2/3 of plasma cholesterol is esterified by

Lecithin cholesterol acyltransferase (LCAT)

33

LCAT reaction

Cholesterol to cholesterol ester

34

Statins mechanism of action

HMG-CoA reductase inhibitor

35

Cholesterol use

needed to 1. maintain cell membrane integrity, and to
2. synthesize bile acid, 3. steroids, and 4. vit D

36

CETP

Cholesterol ester transfer protein

37

CETP function

Mediates transfer of cholesterol esters to other lipoprotein particles and TGs to HDL

38

type of lipases

1. Pancreatic lipase
2. Lipoprotein lipase (LPL)
3. Hepatic TG lipase
4. Hormone sensitive lipase

39

type of lipases and their action

1. Pancreatic lipase --> Degradation of dietary triglycerides in small intestine
2. Lipoprotein lipase (LPL) --> Degradation of TG circulating In chylomicrons and VLDLs. Found on vascular endothelial surface
3. Hepatic TG lipase --> Degradation of TG remaining in IDL
4. Hormone sensitive lipase --> Degradation of TG stored in adipocytes

40

Nascent HDL is produced from

Liver, intestine

41

Nascent to mature HDL - enzyme

Lecithin cholesterol acyltransferase (LCAT)

42

mature HDL - next step

CETP (Cholesterol ester transfer protein): mediates transfer of cholesterol esters to other lipoproteins particles (to VLDL, IDL, LDL)

43

Major apolipopoteins - types

E, A-I, C-II, B-48, B-100

44

Lipd particles

1. Chylomycron
2. Chylomycron remnants
3. VLDL
4. IDL
5. HDL
6. LDL

45

Apolipoprotein E function

Mediates remnant uptake

46

Apolipoprotein E is found at (particles)

1. Chylomycron
2. Chylomycron remnants
3. VLDL
4. IDL
5. HDL
(all except LDL)

47

Apolipoprotein A-1 function

Activates Lecithin cholesterol acyltransferase (LCAT) -- Cholesterol to cholesterol ester

48

Apolipoprotein A-1 is founded

Chylomicrons
HDL

49

Apolipoprotein C-II function

Lipoprotein lipase cofactor

50

Apolipoprotein C-II is founded

Chylomicrons, VLDL, HDL

51

Apolipoprotein B-48 function

Mediates chylomicrons secretion

52

Apolipoprotein B-48 is founded

1. Chylomycron
2. Chylomycron remnants

53

B100 function

Binds LDL receptor
Composition and secretion of VLDL

54

B100 is founded

VLDL
IDL
LDL

55

Lipoproteins are composed of

Varying proportions of cholesterol, TGs and phospholipids

56

Lipoproteins that carry the most cholesterol

LDL
HDL

57

Transports cholesterol from liver to tissues

LDL

58

Transports cholesterol from tissues to the liver

HDL

59

Chylomicrons function / mechanism / source

secreted by Intestinal epithelial cells --> Deliver dietary TGs to peripheral tissue and becomes chylomicron remnants (by LPL) --> Chylomicron remnants (mostly depleted of their TGs) --> Deliver cholesterol to liver

60

VLDL function / source

secreted by liver --> Delivers hepatic TGs to peripheral tissue

61

IDL function / source

formed in the degradation of VLDL (by LPL) --> Delivers TGs and cholesterol to liver

62

LDL - function / source

Formed in the degradation of IDL (by HL in the liver and the peripheral tissue). Delivers hepatic cholesterol to peripheral tissues --> taken up by target cells via receptor-mediated endocytosis

63

HDL function

1. Cholesterol transport from cholesterol transport from peripheral tissue to liver
2. Act as a repository for apoC and apoE (needed for chylomicrons and VLDL metabolism)

64

......increases HDL synthesis

Alcohol

65

HDL is secreted from

Liver
Intestine

66

Familial dyslipidemias - types and mode of inheritance

- type 1 (Hyperchylomicronemia) - AR
- type 2a (hypercholesterolemia) - AD
- type 4 (Hypertriglyceridemia) - AD

67

Familial dyslipidemias - type 1 (Hyperchylomicronemia) - pathogenesis

LPL or APO C-II deficiency

68

Familial dyslipidemias - type 1 (Hyperchylomicronemia) - labs

- Increased 1. Chylomycrons, 2. TG, 3. cholesterol in blood
- Creamy layer is supernatant

69

Familial dyslipidemias - type 1 (Hyperchylomicronemia) - clinical presentation

1. Pancreatitis
2. Hepatosplenomegaly
3. eruptive/pruritic xanthomas
(NO HIGH RISK FOR ATHEROSCLEROSIS)

70

Familial dyslipidemias - type 2a (hypercholesterolemia) - pathogenesis

Absent or defective LDL receptors

71

Familial dyslipidemias - type 2a (hypercholesterolemia) - lab

High 1. LDL 2. cholesterol

72

Familial dyslipidemias - type 2a (hypercholesterolemia) - values of cholesterol

heterozygotes --> 300mg/dl
homozygous --> 700+ mg/dl

73

Familial dyslipidemias - type 2a (hypercholesterolemia) - heterozygous vs homozygous according to frequency and values of cholesterol

heterozygotes --> 1:500 --> 300mg/dl
homozygous --> very rare --> 700+ mg/dl

74

Familial dyslipidemias - type 2a (hypercholesterolemia) - clinical presentation

- accelerated atherosclerosis (may have MI before 20)
- tendon (Achilles) xanthomas
- corneal arcus

75

Familial dyslipidemias - type 4 (Hypertriglyceridemia) - pathogenesis

Hepatic overproduction of VLDL

76

Familial dyslipidemias - type 4 (Hypertriglyceridemia) - labs

- High 1. VLDL, 2. TG
- Hypertriglyceridemia (more than 1000)

77

Familial dyslipidemias - type 4 (Hypertriglyceridemia) - clinical presentation

pancreatitis

78

Familial dyslipidemias - types and pathogenesis (and mode of inheritance)

- type 1 (Hyperchylomicronemia) - AR --> LPL or apoC-II deficiency
- type 2a (hypercholesterolemia) - AD --> Absent or deficient LDL receptors
- type 4 (Hypertriglyceridemia) - AD --> Hepatic overproduction of VLDL

79

Familial dyslipidemias - types and clinical presentation

- type 1 (Hyperchylomicronemia) --> pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas
- type 2a (hypercholesterolemia) --> accelerated atherosclerosis (may have MI before 20), tendon (Achilles) xanthomas, corneal arcus
- type 4 (Hypertriglyceridemia) --> pancreatitis

80

Fatty acid metabolism 1ry occurs in

1. liver
2. lactating mammary glands
3. adipose tissue

81

fatty acid synthesis

citrate (mit) --> to cytoplasm through mit membrane --> acetyl-coa (ATP citrate)
acetyl coa + Biotin + CO2 --> Malonyl-CoA -->
fatty acid synthesis (palmitate, a 16C FA)

82

Medium-chain acyl-coa dehydrogenase deficiency - treatment

treat by avoiding fasting