Fatty Acid Metabolism Flashcards

1
Q

How are Fatty Acids named?

A

Either alpha, beta convention (start near carbonyl)
or
omega convention (start at end). Ex omega 3 FAs have a double bond from 3-4 carbon from the end.

Most fatty acids have an even number of carbons. (#carbon:#double bond) .

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2
Q

Describe the structure of palmitate.

A

Palmitate is a saturated fatty acid with 16 carbon atoms and no double bonds, represented as (16:0).

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3
Q

Define unsaturated fatty acids.

A

Unsaturated fatty acids contain one or more double bonds between carbon atoms, which can affect their physical properties.

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4
Q

How does the presence of double bonds affect the melting point of fatty acids?

A

The melting points of fatty acids are generally higher if they have longer carbon chains and are saturated, while unsaturated fatty acids tend to have lower melting points.

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5
Q

Explain the difference between cis and trans fatty acids.

A

Cis fatty acids
Have hydrogen atoms on the same side of the carbon double bond, which causes the carbon chain to kink. Cis fatty acids are found in natural foods like nuts, fish, and corn oil. They are generally considered beneficial for human health because they can help keep the heart healthy.

Trans fatty acids
Have hydrogen atoms on opposite sides of the carbon double bond, which makes the fat more linear and rigidly packed. Trans fatty acids are mostly created during the hydrogenation process, which stabilizes polyunsaturated oils to keep them solid at room temperature. They are not essential and have no known health benefit. Trans fats are typically found in hydrogenated oils.

Trans fats can raise “bad” cholesterol and lower “good” cholesterol, which can increase the risk of heart disease. The more trans fats eaten, the greater the risk of heart and blood vessel disease.

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6
Q

What is the significance of polyunsaturated fatty acids?

A

Polyunsaturated fatty acids have multiple double bonds that are typically three carbons apart, which can influence their health effects and physical properties.

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7
Q

How does the carbon chain length affect the properties of fatty acids?

A

Longer carbon chains in fatty acids generally lead to higher melting points and can influence their physical state at room temperature.

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8
Q

Define saturated fatty acids and provide an example.

A

Saturated fatty acids have no double bonds between carbon atoms. An example is stearic acid, represented as (18:0) with 18 carbon atoms.

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9
Q

Describe the impact of trans fatty acids on health.

A

Trans fatty acids are considered bad for cholesterol levels and can increase the risk of heart disease.

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10
Q

What is the chemical representation of oleate?

A

Oleate is an unsaturated fatty acid with 18 carbon atoms and one double bond, represented as (18:1).

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11
Q

Explain the notation used for fatty acids, such as (16:0) or (18:1).

A

The notation indicates the total number of carbon atoms followed by the number of double bonds in the fatty acid.

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12
Q

Define triacylglycerols.

A

Triacylglycerols, also known as triglycerides, are a type of fat found in the body, primarily stored in adipose (fat) cells.

They are composed of 3 fatty acids and glycerol esterified together.

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13
Q

Describe the energy content of triacylglycerols compared to glycogen.

A

Fatty acids are considered more reduced than glycogen because their carbon atoms have more hydrogen bonds and fewer oxygen atoms compared to the carbon atoms in glycogen, meaning they have a greater potential to release energy when oxidized during metabolism; essentially, fatty acids have a higher “reduction state” due to their chemical structure, allowing them to store more energy per gram than carbohydrates like glycogen

Triacylglycerols are more reduced so they provide more energy than glycogen, offering 9 kcal/g compared to glycogen’s 4 kcal/g.

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14
Q

How do triacylglycerols differ from glycogen in terms of water content?

A

Triacylglycerols contain no water, while glycogen has a water content of 2:1 water to glycogen.

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15
Q

Explain significance of the ratio of triacylglycerols to glycogen in energy storage.

A

15 kg of triacylglycerols can provide the energy equivalent of 90 kg of glycogen, highlighting the efficiency of fat as an energy storage form.

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16
Q

Fatty Acid Degradation vs Synthesis, which is more significant and common?

A

Degradation because we have energy needs every day. The fat we eat daily gets degraded and used as energy. Synthesis only occurs if there’s excess.

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17
Q

What role do lipases play in the metabolism of triacylglycerols?

A

Lipases are enzymes that break down triacylglycerols into glycerol and fatty acids, facilitating their use as energy.

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18
Q

How does insulin influence the synthesis of triacylglycerols?

A

Insulin inhibits lipases to decrease Fatty Acid Degradation

Insulin promotes the synthesis of triacylglycerols, aiding in fat storage and energy regulation.

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19
Q

Describe the relationship between epinephrine, glucagon, and triacylglycerol metabolism.

A

Epinephrine and glucagon stimulate lipases to break down triacylglycerols, promoting the release of fatty acids for energy use. They also inhibit FA synthesis.

Think: When you’re fasting and run out of glucose, you’re body breaks down fat.

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20
Q

What is the significance of glycerol in energy metabolism?

A

Glycerol can be converted into dihydroxyacetone phosphate (DHAP), which can enter glycolysis or gluconeogenesis, contributing to energy production.

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21
Q

How are fatty acids transported to the liver and muscle tissues?

A

Fatty acids are transported to the liver (and muscle tissues) by serum albumin, a protein that binds to fatty acids in the bloodstream.

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22
Q

Explain the process of fatty acid activation before entering the mitochondrial matrix.

A

Fatty acid activation involves the conversion of fatty acids into acyl-CoA using ATP, which prepares them for subsequent metabolism in the mitochondrial matrix.

A synthestase is an enzyme that uses ATP. Synthase doesn’t need ATP generally.

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23
Q

How does beta-oxidation contribute to energy production?

A

Beta-oxidation is the process by which fatty acids are broken down in the mitochondrial matrix to produce acetyl-CoA, NADH, and FADH2, which are used in the citric acid cycle and oxidative phosphorylation for ATP production.

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24
Q

How does acyl-CoA enter the mitochondrial matrix?

A

Acyl-CoA enters the mitochondrial matrix by first being converted to palmitoyl-carnitine through the action of carnitine palmitoyl transferase I, allowing long-chain fatty acids to cross the mitochondrial membrane.

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25
Q

Define the role of carnitine in fatty acid metabolism.

A

Carnitine facilitates the transport of long-chain fatty acids into the mitochondrial matrix by forming palmitoyl-carnitine, which can cross the mitochondrial membrane.

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26
Q

What inhibits the transport of long-chain fatty acids into the mitochondrial matrix?

A

The transport of long-chain fatty acids into the mitochondrial matrix is inhibited by malonyl-CoA, which is a product of fatty acid synthesis.

This is a form of negative feedback regulation

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27
Q

Do short and medium-chain fatty acids require carnitine for mitochondrial entry?

A

No, short and medium-chain fatty acids can enter the mitochondrial matrix directly without the need for carnitine.

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28
Q

How can muscle pain and weakness be related to carnitine palmitoyl transferase II deficiency?

A

Muscle pain and weakness can occur due to the inability to properly metabolize fatty acids, leading to energy deficits in muscle cells, which may result in rhabdomyolysis.

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29
Q

Define rhabdomyolysis and its potential consequences.

A

Rhabdomyolysis is a condition characterized by the breakdown of muscle tissue, releasing myoglobin into the bloodstream, which can lead to kidney damage and other serious complications.

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30
Q

Describe what conditions would reveal a carnitine palmitoyl transferase I or II deficiency in the body.

A
  • High Fat Diet
  • Fasting; spaced out meals
  • High Activity Lifestyle
31
Q

What dietary changes might help manage symptoms of carnitine palmitoyl transferase II deficiency?

A

A diet low in long-chain fatty acids and higher in carbohydrates may help manage symptoms by reducing the reliance on fatty acid metabolism for energy.

Also higher frequency meals.

32
Q

Describe the steps of beta oxidation. Keep it simple.

A

Beta carbon on the fatty acid is oxidized into a carbonyl then cleaved to remove 2 carbons as Acetyl coA, which can enter TCA and oxidative phosporylation. This repeats until all carbons are used up.

33
Q

Here is a more detailed image of the beta oxidation mechanism. What is the name of the enzyme that catalyzes the first oxidation? The last step is not a hydrolyis but a ________.

A

Acyl CoA dehydrogenase; Thiolysis

34
Q

Define odd chain fatty acids.

A

Odd chain fatty acids are fatty acids that contain an odd number of carbon atoms, which results in the production of a 3 chain intermediate called propionyl-CoA during beta-oxidation.

35
Q

How does methyl malonyl-CoA mutase help us break down odd chain fatty acids?

A

The propionyl-Coa from the odd chain FA is converted to methyl malonyl-CoA and Methyl malonyl-CoA mutase is an enzyme that converts methyl malonyl-CoA to succinyl-CoA, which can enter the TCA cycle.

36
Q

Methyl malonyl-CoA mutase uses which important vitamin as a coenzyme?

A

Vitamin B12

37
Q

What is unique about Vit B12’s structure?

A

It has a metal-carbon bond to cobalt. The only known metal-carbon bond in biochemistry.

38
Q

Describe the role of intrinsic factor in relation to Vitamin B12.

A

Intrinsic factor is a protein produced in the gut that binds to Vitamin B12, facilitating its transport and absorption in the body.

Intrinsic Factor can decline in old age leading to deficiency (Pernicious anemia).

39
Q

Where is Vit B12 made? How do we get it in our system? Which diets are low in it? How can we treat people who are low in Vit B12?

A
  • Made by bacteria in guts of animals
  • Instrinsic factor binds and helps us absorb it from animal products like liver
  • Vegans; can get B12 injections
40
Q

What metabolite’s presence indicates inadequate levels of Vitamin B12?

A

The presence of methylmalonic acid (MMA) increases when Vitamin B12 levels are inadequate.

41
Q

Why is it preferable to test for an increase in methylmalonic acid rather than a decrease in Vitamin B12 concentration?

A

Testing for an increase in methylmalonic acid is preferable because it provides a more sensitive indicator of Vitamin B12 deficiency, as MMA levels rise when B12 is insufficient, even before B12 levels drop significantly.

Lets you know if you have a functional amount or not.

42
Q

Can you perform beta oxidation on unsaturated fatty acids?

A

Yes, there’s an ezyme that will move double bonds to the 2-3 Carbon position for beta oxidation

43
Q

Describe the ATP yield from one molecule of palmitate (16:0).

You don’t need to know this

A

One molecule of palmitate yields a total of 106 ATP: 80 ATP from 8 Acetyl-CoA, 10.5 ATP from 7 FADH2, and 17.5 ATP from 7 NADH, minus 2 ATP for fatty acid activation.

44
Q

Define the role of Acetyl-CoA in ATP production from fatty acids.

A

Acetyl-CoA is produced from fatty acids like palmitate and enters the TCA cycle, contributing to the generation of ATP through the production of CO2, FADH2, and NADH.

45
Q

How do fatty acids differ from triacylglycerols in terms of glucogenic potential?

A

Fatty acids are not glucogenic, meaning they cannot be converted into glucose, while triacylglycerols can be glucogenic through the glycerol component, which can be converted to glucose.

46
Q

Explain the process of fatty acid activation and its ATP cost.

A

Fatty acid activation involves the conversion of fatty acids to acyl-CoA, which costs 2 ATP (from AMP + 2 Pi).

47
Q

What is the significance of the statement ‘You can’t make glucose from acetyl-CoA’?

A

This statement highlights that Acetyl-CoA cannot be converted back into glucose, as it leads to the production of CO2 in the TCA cycle.

48
Q

How many NADH and FADH2 are produced from the breakdown of palmitate?

A

The breakdown of palmitate produces 7 FADH2 and 7 NADH.

1 fadh2 and 1 nadh is made per cycle

49
Q

Describe the conversion of glycerol in the context of glucose production.

A

Glycerol can be converted to dihydroxyacetone phosphate (DHAP), which can then be converted into glucose, making it glucogenic.

50
Q

What are the end products of the TCA cycle when Acetyl-CoA is utilized?

A

The end products of the TCA cycle when Acetyl-CoA is utilized are 2 CO2, FADH2, and NADH.

51
Q

Describe the role of medium chain-length acyl-CoA dehydrogenase in fatty acid metabolism.

A

It is the first step in beta-oxidation and acts on fatty acid chains that are 6 to 12 carbons long.

52
Q

How does medium chain-length acyl-CoA dehydrogenase deficiency manifest during fasting?

A

It can lead to coma in severe cases due to hypoketotic hypoglycemia.

53
Q

Define hypoketotic hypoglycemia and its significance in fatty acid metabolism diseases.

A

Hypoketotic hypoglycemia is a condition characterized by low ketone bodies and low blood sugar, often seen in fatty acid metabolism disorders.

54
Q

What is the incidence rate of medium chain-length acyl-CoA dehydrogenase deficiency?

A

It occurs in approximately 1 in 10,000 individuals.

55
Q

How is medium chain-length acyl-CoA dehydrogenase deficiency related to sudden infant death syndrome (SIDS)?

A

It is implicated in about 10% of SIDS deaths.

56
Q

Describe the role of ketone bodies in the body. Why not just send acetyl-CoA into bloodstream?

A

Ketone bodies serve as transportable forms of Acetyl-CoA, primarily produced by the liver, and are utilized by various tissues such as brain, muscle, renal cortex, and heart (prefers them to glucose), especially during fasting and starvation.

Acetyl-CoA cannot directly travel through the bloodstream because of its large, highly reactive structure, so when the body needs to transport energy from fatty acid breakdown, it converts acetyl-CoA into ketone bodies, which are smaller and more readily cross the blood-brain barrier, allowing them to be used as an energy source by other tissues when glucose is low.

57
Q

How does the brain utilize ketone bodies during fasting?

A

During fasting, the brain cannot take up fatty acids and instead relies on ketone bodies, which are converted to Acetyl-CoA for energy.

58
Q

Define the conditions under which ketone bodies increase in the body.

A

Ketone bodies increase during starvation and in type I diabetes due to elevated fatty acid oxidation and reduced glucose availability.

59
Q

Fatty acid synthesis occures in the cytoplasm and requires Acetyl-CoA, which can not pass through membranes. How do we get Acetyl-CoA out of the mitochondrial matrix and into the cytoplasm?

A

Acetyl-CoA combines with OAA to become citrate (think TCA), move into the cytoplasm, then converted back so it can be used.

60
Q

A lot of NADPH is needed to make fatty acids (anabolic). How is NADPH generated during the process of fatty acid synthesis?

A

NADPH is generated through the action of the malic enzyme, which converts malate to pyruvate, producing NADPH and CO2 in the process.

61
Q

Describe the anaplerotic reactions in the context of fatty acid synthesis.

A

Anaplerotic reactions replenish intermediates in the citric acid cycle, which are necessary for the synthesis of fatty acids and other metabolic processes.

62
Q

In which tissue does the majority of fatty acid production take place?

A

The majority of fatty acid synthesis occurs in the liver. This is because the liver is the primary site for de novo lipogenesis, the process of creating new fatty acids from acetyl-CoA.

Also takes place in mammary glands and adipose tissue.

63
Q

Define the structure of fatty acid synthase.

A

Fatty acid synthase is a mega enzyme with multiple activities, facilitating various steps in fatty acid synthesis.

64
Q

The first step of fatty acid synthesis is the activation of Acetyl-CoA. Which enzyme catalyzes this rxn and what is formed?

A

Acetyl CoA Carboxylase uses CO2 to add a carboxyl group to Actetyl CoA. Biotin is involved as a Co2 donor. This forms malonyl-CoA.

65
Q

What key molecules inhibit and activate Acetyl CoA Carboxylase?

A

inhibit: Epi/glucagon, palmitoyl-CoA
activate: Insulin, Citrate

66
Q

Describe the process of converting acetyl-CoA to palmitoyl-CoA.

A

The conversion involves the sequential addition of two-carbon units from malonyl-CoA to the growing fatty acid chain, ultimately producing palmitoyl-CoA.

67
Q

Describe the role of Acyl Carrier Protein (ACP) in fatty acid synthesis.

A

ACP serves as a carrier for acyl groups during the fatty acid synthesis process, facilitating the transfer of acyl chains.

68
Q

Define the function of the Condensing Enzyme in fatty acid synthase.

A

The Condensing Enzyme catalyzes the condensation reaction between Acetyl-CoA and malonyl-CoA, forming a longer carbon chain.

69
Q

Explain the significance of NADPH in fatty acid synthase reactions.

A

NADPH provides the reducing power needed for the biosynthesis of fatty acids, specifically used in two reactions during the synthesis process.

70
Q

How does the process of fatty acid synthesis repeat until palmitate is formed?

A

The process involves repeated cycles of condensation, reduction, dehydration, and another reduction, using malonyl-CoA and Acetyl-CoA until the desired chain length is achieved.

71
Q

How many ATP molecules are invested to raise the energy level during fatty acid synthesis?

A

1 ATP each round to create malonyl-CoA.

Seven ATP molecules are invested to raise the energy level during palmitate synthesis.

72
Q

Explain the role of NADPH in fatty acid synthesis.

A

NADPH provides reducing power for fatty acid synthesis, with 8 NADPH generated from the malic enzyme and 6 from the Pentose Phosphate pathway.

73
Q

What is the significance of linoleate (12:2) and linolenate (18:3) in fatty acid metabolism?

A

Linoleate (18:2) and linolenate (18:3) are essential fatty acids that serve as precursors to prostaglandins. We can’t produce fatty acids with double bons past C-9 so we have to eat them.

74
Q

Identify where longer and unsaturated fatty acids are synthesized.

A

Longer and unsaturated fatty acids are synthesized on the cytoplasmic side of the endoplasmic reticulum and in peroxisomes.