Lipid Metabolism I Flashcards

0
Q

How many kcal does the body get from the major fuel sources?

A

100,000 - TAG
600 - Glycogen
40 - Glucose

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1
Q

What are the major lipids present in human diet (plan and animal sources)?

A

Triacylglycerols (TAG)

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2
Q

What is a TAG composed of?

A

Glycerol with triacyl

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3
Q

What does lipid digestion depend on?

A

Length of fatty acids in the TAG

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4
Q

What enzymes digest short and medium chain FA in TAG?

A

Lingual and gastric lipase

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5
Q

How many carbons in a FA is considered short and medium chain length?

A

< 12 carbons.. These TAGs can be found in milk

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6
Q

What are fats emulsified by and where?

A

Bile salts in the small intestine

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7
Q

What is emulsification?

A

Suspension into small particles in the aqueous enfivronment

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8
Q

What is the polarity of bile salts?

A

amphipathic

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9
Q

What releases bile salts and other pancreatic enzymes?

A

Contraction of gall bladder

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10
Q

What gut hormone stimulates the contraction of gall bladder?

A

Cholecystokinin

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11
Q

Where does most of the digestion happen?

A

Small intestines

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12
Q

Why do fats cluster together?

A

Very hydrophobic

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13
Q

Why are bile salts necessary to digest lipids?

A

Because fats cluster together and its difficult for the lipase to get to it. Bile salts aid in opening

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14
Q

What is the purpose of emulsification?

A

Greatly increases the surface area of fats

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15
Q

After being emulsified what do fats become the substrate of?

A

pancreatic lipase

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16
Q

What hormone is released in response to acidic material?

A

Secretin

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17
Q

What does secretin cause? What is the purpose?

A

Release of bicarbonate which increases the pH to 6, this is optimal for intestinal enzymes

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18
Q

What lengths of FAs do pancreatic lipase digests?

A

All lengths

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19
Q

What are the products of pancreatic lipase?

A

Forms FA and 2-monoacylglycerol (2-MAG)

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20
Q

What does the pancreas produce that removes FA from cholesterol esters?

A

Esterase

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21
Q

What does the pancreas produce to remove FA from phospholipids?

A

Phospholipase A2

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22
Q

Where are short and medium chain FA absorbed into?

A

Intestinal epithelial cells

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23
Q

After the FA chains are absorbed into intestinal epithelial cells, how doe they reach the liver?

A

They enter portal blood and are transported into liver bound to serum albumin

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24
What are log chains of FAs and 2-MAGs packed into?
Micelles and emulsified by bile salts
25
What other lipids are also packaged into micelles?
Cholesterol, lyso PLs, and fat soluble vitamins
26
What are lipids absorbed across what, and where do the bile salts go?
Lipids are absorbed across microvilli and bile salts are left in gut to be recycled
27
Once in the intestinal cells, what are condensed to form TAG? Where does this occur in the intestinal cells?
MAGs and FA. Occur in the smooth ER
28
Once TAG is formed in the intestinal cells what are they packaged into?
Chylomicrons
29
What do chylomicrons contain in addition to TAG?
proteins and phospholipids | Cholesterol and fat soluble vitamins
30
What is the major apoprotein in intestinal cells?
B48
31
What is secreted by the intestinal cells via exocytosis?
Nascent chylomicrons
32
Where are nascent chylomicrons secreted to?
Lymphatic system
33
How do nascent chylomicrons enter the blood?
Thoracic duct
34
What is expressed on a mature chylomicron in the blood?
ApoE and ApoCII
35
What recognizes ApoE?
Receptors on surface of liver cells allowing endocytosis
36
What does ApoCII activate?
Activates lipoprotein lipase present on capillary endothelial cells in muscle and adipose tissue which digests chylomicrons
37
Why must lipoprotein lipase break down the chylomicrons?
Because chylomicrons cannot go through plasma membrane
38
What does lipoprotein lipase do to chylomicrons?
Hydrolyzes TG in the chylomicrons and FA is released.
39
Free FA are transported to what cells?
Adipocytes where TG are synthesized and stored in lipid droplets
40
What are the required 3 steps to use FA as fuel?
Mobilization - TAGs broken to FA and glycerol, released from adipose tissue and transported to energy requiring tissue Activation - Fatty acids must be activated and transported into mitochondria Degradation - Stepwise breakdown of FA into acetyl CoA which is then processed in TCA cycle
41
What two hormones mobilized FA from adipocytes?
Epinephrine and glucagon
42
How are hormones involved in the mobilization of FA?
Glucagon and epinephrine activate G protein which then goes to activate adenylate cyclase Adenylate cyclase converts ATP to cAMP. cAMP activates protein kinase A Protein kinase A activates perilipin and HS lipase. Perilipin activates ATGL with coactivator which converts TAG to DAG and HS lipase converts DAG to MAG MAG lipase breaks down MAG into Glycerol and FA
43
Where does fatty acid activation occur?
In the cytosol
44
How are long chain fatty acyl CoAs carried across the mitochondri membranes?
Carnitine shuttle
45
Where does Beta-oxidation occur?
Primarily in mitochondrial matrix
46
What is the first reaction in any FA metabolism?
converting FA into Acyl CoA with Acyl-CoA synthetase
47
What does the first reaction of FA metabolism do?
Traps FA in cells Makes it metabolically active PPi hydrolysis makes it irreversible
48
Once activated, what transfers Acyl CoA into the mitochondrial matrix?
Acyl Carnitine Translocase and carnitine
49
Explain the steps of FA beta oxidation in the mitochondrial matrix
Step 1: Acyl CoA is oxidized by Acyl CoA dehydrongenase. Becomes trans enoyl CoA and produces 1.5 ATP (FADH2) Step 2: Trans enyl CoA is hydrated and converted to L hydroxyacyl Step 3: L hydroxyacyl is oxidized into 3-ketoacyl CoA. Produces 2.5 ATP (NADH2) Step 4: 3-keytoacyl Coa is thiolysized into acyl CoA and Acetyl CoA. Acetyl-CoA = 10ATP
50
What is thiolysis reaction
It is a lytic reaction
51
The breakdown of paalmitoyl CoA will yield how much ATP?
108 ATP but net is 106 7 repetitions of B-oxidation spiral 4 ATP from NADH2 and FADH2 * 7 + 8 Acetyle CoA * 10 ATP = 108
52
Unsaturated and odd chain FA degradation require what 2 additional enzymes?
isomerase and reductase
53
What is an unsaturated FA?
Has double bonds
54
Odd numbered double bonds are handled by what enzyme?
isomerase
55
Even numbered double bonds are handled by what enzymes?
Reductase and isomerase
56
What do odd chained unsaturated FA give rise to?
Propionyl CoA and acetyl CoA
57
What is the fate of propionyl CoA?
Converted to succinyl CoA and then enters TCA cycle | Conversion requires vitamin B12 (cobalamin)
58
Describe the concept of the breakdown of palmitoleoyl CoA
Palmitoleoyl CoA is a double bond FA with its double bond between C9 and C10. The first three cuts are normal like saturated fatty acids but the fourth cut comes to a cis 3 enoyl CoA. This is not a substrate for acyl CoA dehydrogenase. So an isomerase comes in and converts the cis into trans and then it can become a substrate
59
What are the roles of isomerase and reductase?
Isomerase switches the enoyl from a cis to a trans. | Reductase deals with odd double bonds to reduce them
60
Where can FA beta oxidation occur other than the mitochondrial matrix?
In the peroxisomes because long chains are unable to be degraded in nmitochondria
61
What is the purpose of beta oxidation in peroxisomes?
To shorten the FA chains so they can go to the mitochondria for mitochondrian oxidation
62
What is used in the first oxidation of peroxisome oxidation?
FAD
63
True or False | ATP is generated in beta oxidation in peroxisomes?
False
64
What is a by product of beta oxidation in peroxisomes?
H2O2 - this is toxic and is degraded into water
65
True or False After the first step with Acyl CoA dehydrogenase, the beta oxidation in peroxisome is similar to beta oxidation in mitochondria?
True
66
What is the fate of Acetyl CoA formed from FA?
Enters the TCA cycle and combines with oxaloacetate to form citrate.
67
What happens if OAA is low due to low carbs?
Acetyl CoA is not used
68
True or false? | Fats burn in the flame of carbohydrates
True
69
When fasting or in diabetes what is the fate of OAA?
Consumed to glucose by gluconeogenesis
70
What happens to the excess Acetyl CoA in the TCA cycle?
Condenses to form ketone bodies
71
How are ketone bodies formed?
2 Acetyl CoA come together to form acetoacetyl CoA. Series of steps converts it to acetoacetate which breaks down to acetone and 3-hyroxybutyrate
72
what uses ketone bodies during starvation and where does it come from?
The heart and kidney cortex prefers ketone bodies. The brain uses ketone bodies in the CAC cycle. Ketone bodies are a soluble form of energy. Brain does not like it but when there is no glucose, glycogen or triglycerides then it switches to ketone bodies Ketones come from the breakdown of TAG in fat cells. The fatty acids go to the liver cells to be converted into ketone bodies. The ketone bodies go to the blood to be transported to the needed tissues.