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POM (Principles of Medicine) > Cell Metabolism II > Flashcards

Cell Metabolism II Flashcards

1
Q

what are the 5 main classes of lipids?

A 
free fatty acids
triacylglycerols
phospholipids
glycolipids
steroids
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2
Q

What are fatty acids?

A

hydrocarbon chains with a terminal carboxylic acid group

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3
Q

What does saturated mean?

A

Absence of double bonds

every carbon atom is attached to 4 other atoms

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4
Q

How are fatty acids stored in the cytoplasm of cells?

A

in the form of triacylglycerols

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5
Q

What are triacylglycerols?

A

Molecules composed of 3 fatty acids attached to a glycerol molecule

attachments: ester linkages

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6
Q

What do the ester linkages do to the carboxylic acid groups?

A

Neutralise them to help keep the pH of cells in a normal range

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7
Q

What are the characteristics of fatty acids?

A

reduced and anhydrous

ideal storage molecules

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8
Q

What does fatty acid metabolism lead to?

A

Acetyl CoA production

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9
Q

how are fats broken down?

A

Fats –> fatty acids –> acetyl CoA (produced in mitochondria)

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10
Q

What are the 3 sources of fats?

A

diet
De novo biosynthesis (liver) (production of fats)
storage deposits in adipose

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11
Q

What are bile salts generated from and where?

A

cholesterol
in the liver
stored in the gal bladder

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12
Q

What are bile salts?

A

They have a hydrophobic part and a hydrophilic part

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13
Q

What is the role of bile salts?

A

Solubilize fatty acids

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14
Q

What happens with bile salts during digestion?

A

they pass from the bile duct into the intestine

they emulsify fats in the intestine, aiding their digestion and absorption of fats and also that of fat-soluble vitamins

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15
Q

what are fat-soluble vitamins?

A

A,D,E and K

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16
Q

What does a lack of bile salts result in?

A

the majority of fats passes through the gut undigested and unabsorbed resulting in steatorrhea (fatty stool)

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17
Q

What is orlistat?

A

A protein inhibitor of gastric and pancreatic lipases

a chemically synthesised derivative of lipstatin, a product of Streptomyces toxytricini

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18
Q

What does orlistat do?

A

reduces fat absorption by 30% which is almost completely excreted by the faecal route

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19
Q

What is it effective in treating?

A

obesity ( for up to 2 years)

main side effects: abdominal pain, urgency to defecate, increased flatus and steatorrhea

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20
Q

How are fats transported around the body?

A

transported in the plasma by lipoproteins which are categorized according to their density

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21
Q

chylomicrons (CM) lipoproteins

A

source: intestines
role: dietary fat transport

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22
Q

very low density lipoproteins (VLDL)

A

source: liver
role: endogenous fat transport

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23
Q

intermediate density lipoproteins (IDL)

A

source: very low density lipoproteins (VLDL)
role: LDL precursor

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24
Q

low density lipoproteins (LDL)

A

source: intermediate density lipoproteins (IDL)
role: cholesterol transport

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25
Q

high density lipoproteins (HDL)

A

source: liver
role: reverse cholesterol transport

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26
Q

What is the chylomicron?

A

a molecule that transports dietary fats

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27
Q

How are dietary products absorbed?

A

by enterocytes

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28
Q

what are enterocytes?

A

cells that line the brush border of the small intestines

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29
Q

what happens to the dietary fats when they’re ingested?

A

triglycerides are resynthesized under the control of several enzymes prior to incorporation into chylomicrons (CM)

30
Q

Where are chylomicrons transported?

A

via the lymphatics and on into the bloodstream

31
Q

When do chylomicrons acquire apoproteins from HDL?

A

following the release of the bloodstream

32
Q

what is the structure of chylomicron?

A

a layer of phospholipid on the outside with embedded apoproteins and triglycerides inside the spherical shape

33
Q

What do lipases breakdown?

A

lipoproteins

34
Q

How do chylomicrons enter the bloodstream?

A

CMs travel from the lacteals of the intestine to the thoracic duct and to the left subclavian vein

35
Q

Where is lipoprotein lipase located?

A

on the capillary endothelial cells lining a variety of tissues including adipose, heart and skeletal muscle

36
Q

What do fatty acids undergo?

A

β-oxidation

37
Q

Where does glycerol return?

A

to the liver for use in gluconeogenesis

38
Q

lifecycle of chylomicrons

A

intestinal villus –> nascent chylomicron –(HDL)–>transfer of apoproteins–> the triglycerides are broken down to glycerol + free fatty acids
chylomicron remnants can pick up more HDL and these are recognised by the liver

39
Q

what is embedded in the chylomicrons membrane and found inside?

A

cholesterol

40
Q

what are cholesterol esters?

A

synthesized in the plasma from cholesterol and the acyl chain of phosphatidylcholine (lecithin) via a reaction catalyzed by lecithin: cholesterol acyltransferase (LCAT)

cholesterol + phosphatidylcholine –(LCAT)–> cholesterol ester + lysophosphatidylcholine

41
Q

life cycle of VLDL, IDL, HDL, LDL

A

liver–> VLDL –(glycerol + ffa)–> lipid-depleted remnant –(transfer of apoproteins HDL)–> IDL –(transfer of CE from HDL)–> LDL which is either taken up by the liver or macrophages

42
Q

What is HDL?

A

“good cholesterol”
take cholesterol from peripheral tissues back to the liver for use or disposal
lower total serum cholesterol

43
Q

What is LDL?

A

“bad cholesterol”
prolonged elevation of LDL levels lead to atherosclerosis (hardening of the arteries)
transport cholesterol synthesised in the liver to peripheral tissues with more than 40% of their weight is made up of cholesterol esters

44
Q

What is the caloric yield from fatty acids?

A

twice as much as carbohydrates

45
Q

STEP 1: β-oxidation of fatty acids reaction

A

fatty acid + ATP + HS – CoA –(ACYL CoA SYNTHETASE)–> acyl CoA + AMP + PPi

ATP –> AMP (adenosine monophosphate)

46
Q

Where does the generation of the Acyl CoA species occur?

A

on the outer mitochondrial membrane

47
Q

What is acyl CoA coupled with to be transported into the matrix?

A

carnitine to form acyl carnitine

48
Q

How are carnitine and acyl carnitine moved to and from the matrix?

A

translocase

49
Q

STEP 2: the carnitine shuttle

A

carnitine+ Acyl CoA–> Acyl carnitine + CoA
enzyme: CARNITINE ACYLTRANSFERASE I
acyl carnitine moved into the matrix
acyl carnitine + CoA –>carnitine + Acyl CoA
enzyme: CARNITINE ACYLTRANSFERASE II
carnitine is moved back out

50
Q

What is primary carnitine deficiency?

A

autosomal recessive disorder
symptoms: cardiomyopathies, muscle weakness, hypoglycemia)
mutation in gene–> reduced ability of cells to take up carnitine needed for β-oxidation of fatty acids

51
Q

What happens in the β-oxidation cycle?

A

The acyl CoA undergoes a sequence of oxidation, hydration, oxidation and thiolysis reactions (collectively called β-oxidation)

this results in the production of one molecule of acetyl CoA and an acyl CoA species which is 2 carbons shorter than the original

52
Q

overall reaction of β-oxidation of palmatic acid?

A

(16 carbon) palmitoyl CoA + 7 NAD+ + 7 H2O + 7 CoA –> 8 acetyl CoA + 7 FADH2 + 7 NADH
7 cycles

53
Q

what does acetyl CoA enter?

A

the TCA cycle only if β-oxidation and carbohydrate metabolism are balanced, since oxaloacetate is needed for entry

54
Q

What happens when fat breakdown predominates?

fasting

A

acetyl CoA forms acetoacetate, D-3-hydroxybutyrate and acetone known as ketone bodies

enzymes: 1: 3-ketothiolase
2: hydroxymethylglutaryl CoA synthase
3: hydroxymethylglutaryl CoA cleavage enzyme
4: D-3-hydroxybutyrate dehydrogenase

55
Q

How many ATP molecules are made from the oxidation of palmitoyl?

A

35 from β-oxidation and 96 from 8 TCA or Krebs cycle= 131

2 ATP are used in acyl CoA so =129 ATP

56
Q

What enzymes are involved in fatty acid biosynthesis?

A

acetyl-CoA and malonyl-CoA

57
Q

What reactions form fatty acids?

A

decarboxylative condensation reactions involving the molecules acetyl-CoA and malonyl-CoA

58
Q

how else is fatty acid biosynthesis called?

A

Lipogenesis

59
Q

What reactions do fatty acids undergo?

A

reduction and dehydration by the sequential action of a ketoreductase (KR), dehydratase (DH), and enol reductase (ER) activity

60
Q

What is the growing fatty acid group linked to?

A

an acyl carrier protein (ACP)

61
Q

what is the overall reaction of fatty acid synthesis?

A

ACTIVATED ACETYL GROUP + ACTIVATED MALONYL GROUP
condensation–> reduction–>dehydration–> reduction–>
ACTIVATED ACYL GROUP ( lengthened by 2 C atoms)

62
Q

What is the overall reaction of fatty acid degradation? (β-oxidation )

A

ACTIVATED ACYL GROUP
oxidation–> hydration–> oxidation–> cleavage–>
ACTIVATED ACYL GROUP (shortened by 2 C atoms) + ACTIVATED ACETYL GROUP

63
Q

Distinctions between synthesis and degradation?

A

carriers: ACP vs CoA
reducing power: NADPH v FAD/NAD+
locations; cytoplasm v mitochondrial matrix

64
Q

Overall reaction of lipogenesis?

A 
Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+ --->
Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+
65
Q

What does the desaturation of fatty acids require?

A

the action of fatty acyl-CoA desaturases

66
Q

What is ∆-9 desaturase?

A

The enzyme that creates oleic acid and palmitoleic acid from stearate and palmitate
it generates a double bond nine carbons from the terminal carboxyl group

67
Q

Where does FA biosynthesis happen in adults?

A

liver, adipose tissue and lactating breast

68
Q

What are Disorders of β-oxidation?
Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD)
c6-c12

A

Autosomal recessive. Predominantly occurring in Caucasians
If undiagnosed, can be fatal
not good at breaking down fatty acids for e
get most cals from carbohydrates
no long fasts (10-12 hours)

69
Q

Fatty acids within deposits are non-esterified and transported by?

A

albium

70
Q

the majority of FA we consume are even chain length

But odd chain length result in?

A

3 c propionyl CoA on final oxidation

undergoes a series of reactions that yields succinyl-CoA which can enter the TCA cycle

POM (Principles of Medicine) (17 decks)

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