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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
high density lipoproteins (HDL)
source: liver role: reverse cholesterol transport
26
What is the chylomicron?
a molecule that transports dietary fats
27
How are dietary products absorbed?
by enterocytes
28
what are enterocytes?
cells that line the brush border of the small intestines
29
what happens to the dietary fats when they're ingested?
triglycerides are resynthesized under the control of several enzymes prior to incorporation into chylomicrons (CM)
30
Where are chylomicrons transported?
via the lymphatics and on into the bloodstream
31
When do chylomicrons acquire apoproteins from HDL?
following the release of the bloodstream
32
what is the structure of chylomicron?
a layer of phospholipid on the outside with embedded apoproteins and triglycerides inside the spherical shape
33
What do lipases breakdown?
lipoproteins
34
How do chylomicrons enter the bloodstream?
CMs travel from the lacteals of the intestine to the thoracic duct and to the left subclavian vein
35
Where is lipoprotein lipase located?
on the capillary endothelial cells lining a variety of tissues including adipose, heart and skeletal muscle
36
What do fatty acids undergo?
β-oxidation
37
Where does glycerol return?
to the liver for use in gluconeogenesis
38
lifecycle of chylomicrons
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
what is embedded in the chylomicrons membrane and found inside?
cholesterol
40
what are cholesterol esters?
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
life cycle of VLDL, IDL, HDL, LDL
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
What is HDL?
"good cholesterol" take cholesterol from peripheral tissues back to the liver for use or disposal lower total serum cholesterol
43
What is LDL?
"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
What is the caloric yield from fatty acids?
twice as much as carbohydrates
45
STEP 1: β-oxidation of fatty acids reaction
fatty acid + ATP + HS -- CoA --(ACYL CoA SYNTHETASE)--> acyl CoA + AMP + PPi ATP --> AMP (adenosine monophosphate)
46
Where does the generation of the Acyl CoA species occur?
on the outer mitochondrial membrane
47
What is acyl CoA coupled with to be transported into the matrix?
carnitine to form acyl carnitine
48
How are carnitine and acyl carnitine moved to and from the matrix?
translocase
49
STEP 2: the carnitine shuttle
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
What is primary carnitine deficiency?
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
What happens in the β-oxidation cycle?
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
overall reaction of β-oxidation of palmatic acid?
(16 carbon) palmitoyl CoA + 7 NAD+ + 7 H2O + 7 CoA --> 8 acetyl CoA + 7 FADH2 + 7 NADH 7 cycles
53
what does acetyl CoA enter?
the TCA cycle only if β-oxidation and carbohydrate metabolism are balanced, since oxaloacetate is needed for entry
54
What happens when fat breakdown predominates? | fasting
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
How many ATP molecules are made from the oxidation of palmitoyl?
35 from β-oxidation and 96 from 8 TCA or Krebs cycle= 131 | 2 ATP are used in acyl CoA so =129 ATP
56
What enzymes are involved in fatty acid biosynthesis?
acetyl-CoA and malonyl-CoA
57
What reactions form fatty acids?
decarboxylative condensation reactions involving the molecules acetyl-CoA and malonyl-CoA
58
how else is fatty acid biosynthesis called?
Lipogenesis
59
What reactions do fatty acids undergo?
reduction and dehydration by the sequential action of a ketoreductase (KR), dehydratase (DH), and enol reductase (ER) activity
60
What is the growing fatty acid group linked to?
an acyl carrier protein (ACP)
61
what is the overall reaction of fatty acid synthesis?
ACTIVATED ACETYL GROUP + ACTIVATED MALONYL GROUP condensation--> reduction-->dehydration--> reduction--> ACTIVATED ACYL GROUP ( lengthened by 2 C atoms)
62
What is the overall reaction of fatty acid degradation? (β-oxidation )
ACTIVATED ACYL GROUP oxidation--> hydration--> oxidation--> cleavage--> ACTIVATED ACYL GROUP (shortened by 2 C atoms) + ACTIVATED ACETYL GROUP
63
Distinctions between synthesis and degradation?
carriers: ACP vs CoA reducing power: NADPH v FAD/NAD+ locations; cytoplasm v mitochondrial matrix
64
Overall reaction of lipogenesis?
``` Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+ ---> Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+ ```
65
What does the desaturation of fatty acids require?
the action of fatty acyl-CoA desaturases
66
What is ∆-9 desaturase?
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
Where does FA biosynthesis happen in adults?
liver, adipose tissue and lactating breast
68
What are Disorders of β-oxidation? Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) c6-c12
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
Fatty acids within deposits are non-esterified and transported by?
albium
70
the majority of FA we consume are even chain length | But odd chain length result in?
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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