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Biochem > Exam3Lec3LipidMetabolismFattyAcidMetabolism > Flashcards

Exam3Lec3LipidMetabolismFattyAcidMetabolism Flashcards

1
Q

Fatty acids are taken up by cells, where they may serve as precursors of what three things?

A

in the synthesis of other compunds, fuels for energy for production, and substrates for ketone body synthesis

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2
Q

What is the major form of energy storage?

A

Fat
stores 100,000 kcal of fuel
release 9 kcal of energy per molecule

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3
Q

What are the intermediates in fatty acid metabolism?

A

Phospholipids( in membranes)
Eicosanoids: this includes prostaglandins and leukotrienes which play a role in physiological regulation

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4
Q

What are some precursors of acetyl coA?

A

glucose to pyruvate, amino acids

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5
Q

What are some products of Acetyl CoA?

A

fatty acids, triglycerides, energy, phospholipids, eicasonoides, ketone bodies, cholesterol (steroid hormones and bile salts)

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6
Q

What is the central intermediate in lipid metabolism?

A

Acetyl CoA

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7
Q

What is the structure of Acetyl CoA?

A
  1. Acetyl group
  2. Coenzyme A ( Beta-mercaptoethylamone, pantothenic avid, 3,5-adenosine diphosphate)
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8
Q

What is the basic structure of fatty acids?

A

A long LINEAR hydrocarbon chain of around 12-24 C , with an EVEN number of carbons and a carboxylic acid group.

even number of carbons in hydrocarbon chain
carboxylic acid group

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9
Q

One system of fatty acid classification is based on the number of what?

A

double bonds

The many fatty acids which occur naturally arise primarily through
variation of chain length and degree of saturation.

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10
Q

No double bonds is classified as what type of fatty acid, and provide an example

A

Saturated fatty acid
EX: stearic acid
18:0

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11
Q

One double bond is classified as what type of fatty acid, and provide an example

A

monounsaturated fatty acid
EX: oleic acid
18:1delta9

most prevalent in human body

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12
Q

All double bond occuring in natural mammalian amino acids is in what configuaration?

A

CIS

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13
Q

Two or more double bonds is classified as what type of fatty acid, and provide an example

A

polyunsaturated fatty acids
EX: linoleic acid
NEVER conjugated
created methylene bridge

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14
Q

Unsaturated fatty acid has what type of backbone, and this is important for what?

A

Bent due to steric hinderance of protons, this is important for the melting point of fatty acid

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15
Q

The more db in fatty acids the ______ the melting point

A

lower

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16
Q

Bends and kinks in polyunsaturated fatty acids are liquid at room temperature, meaning that is takes ____ heat to melt

A

less

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17
Q

What are the 5 naturally occurring fatty acids and their carboxyl reference?

A
  1. palmitic acid-16:0
    2.stearic acid-18:0
    3.oleic acid-18:1 delta^9
    4.linoleic acid-18:2 delta^9,12
    5.linolenic acid-18:3 delta^9,12,15
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18
Q

What is the first carbon, second carbon, and last carbon following the carboxyl carbon in a fatty acid chain?

A

1st carbon=alpha carbon
2nd carbon=beta carbon
last carbon (farthest from the carboxyl grp)=omega carbon

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19
Q

Fatty acid synthesis occurs primarily in the cytoplasm of which tissues?

A

liver, adipose (fat), CNS, lactating mammary gland

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20
Q

De Novo FA synthesis comes from

A

glucose (starting compound)

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21
Q

____is the major source of acetyl CoA for fatty acid synthesis

A

glucose

Acetyl CoA for fatty acid synthesis COMES mostly from glycolytic breakdown of glucose.

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22
Q

What is the reaction for the de novo synthesis of Fatty Acids?

A

Glucose–> 2 pyruvate (through glycolysis.
2 pyruvate–> 2 acetyl CoA (by pyruvate dehydrogenase)

8 acetyl CoA + 7 ATP + 14 (NADPH + H+) -> palmitate (16:0) + 8 CoA + 7 (ADP + Pi) + 14 NADP+ + 6 H2O

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23
Q

Glucose yield Acetyl CoA, explain this process

A
  1. Glucose is degraded to pyruvate by glycolysis
  2. Pyruvate moves to mitochondria and pyruvate dehydrogenase oxidatively decarboxylated pyruvate forming acetyl CoA. THIS IS THE PDH COMPLEX
    3, Acetyl CoA can serve as a substrate for citrate synthesis
  3. Citrate can leave mitochondria and go to cytosol (where fatty acid is made) and ATP citrite lyase splits citrate into Acetyl Coa and OAA
24
Q

What is the conditions inducive to the synthesis of FA?

A

The ratio of insulin to glucagon must be high (high insulin, low glucagon)

fed state-you make FA

25
Q

What is the acetyl CoA carboxylase reaction?

A

Acetyl CoA (2c) + Bicarb (1c)—> malonyl CoA (3c)

enzyme: Acetyl CoA Carboxylase (ACC) with Biotin as a co-factor

this is how we acquire malonyl coA

26
Q

What is the RLE in de novo fatty acid synthesis?

A

Acetyl CoA Carboxylase (ACC) with Biotin as a co-factor

27
Q

What are the isoforms of ACC and specify which tissues they occur in

A

Alpha and Beta
alpha: liver, adipose tissue, lactating mammary
beta: skeletal muscle, heart muscle, liver

28
Q

What are the mechanisms of regulation of ACC?

A

Phosphorylaton (inactive)
1. Mediated by AMP-dependent protein
2. Kinase and Protein Kinase A

Dephosrylation (Active)
1. Mediated by phosphoprotein phosphotase

Allosteric regulation
1. Citrate is positive effector
2. Long chain FA negative effector

29
Q

Which ACC isoform is mostly involved in FA synthesis?

A

ACC alpha

30
Q

Is citrate a physiological regulator of ACC?

A

NO

31
Q

If we have a high insulin/glucagon ratio, which regulation occurs?

A

Phosphoprotein phosphatase is activated, this de-phosphorylates and the reaction is now activated

32
Q

What is the role of Carbohydrate-Responsive element binding protein ChREBP) as a regulator of lipid synthesis in the liver?

A

ChREBP is a major glucose-responsive transcription factor. Expression of ChREBP gene is induced in liver in response to increased glucose uptake

33
Q

Explain how ChREBP contributes to the transcription of lipogenic genes?

A
  1. High glucose uptake, X5P dephosphorylates ChREBP.
  2. ChREBP transloates to the nucleus where it binds to Carbohydrates response elements (ChoREs).
  3. ChREBP acts with Sterol Response Element Binding protein (SREBP).
  4. SREBP binds with SRE (as well as incr GK) and this turns on lipogenic genes such as acetyl coA carboxylase and fatty acid synthetase to make more fat

acts synergestically with SREBP

34
Q

What are 7 examples of lipogenic genes?

A

1.acetyl coA carboxylase
2.fatty acid synthetase
3.ATP citrate lyase
4.Glucose-6-dehydrogenase
5.6-phosphate-gluconate dehydrogenase
6.Malic enzyme
7.Fatty acid desaturase

35
Q

Fatty acid synthase resides in the ____ and under physiological conditions it exsists as a ____

A

cytosol, homodimer

must be in dimeric configuration (“head to head”)

36
Q

We have 2 identical peptides of fa synthase, How many enzymatic activity do we have on each polypeptide chain?

A

7 enzymatic activities per polypeptide,

this enhances synthetic process

37
Q

Describe the process of creating carbon chain w/ fatty acid synthase

A
  1. You have your fatty acid synthase with two components: cysteine residue and ACP residue. We made Acetyl coa so it comes in and is added to the ACP esterifying it
  2. The acetyl coA that was just added to the acp side is then transfereed to the cys side.
  3. We made malonyl coA so that comes in and is added to the ACP side
  4. Co2 is lost from bicarbonate. Because we lost a carrbon from ACP, cys transfers its carbon grp to ACP
  5. NADPH comes in (this came from maleic enzyme or PPP) and added 2 H to ACP side
  6. ACP side is hydrolyzed, so H2O is lost, and we creates a double bond.
  7. NADPH comes in again and we now have 2 CH2 with no double bond so we creates a 4-C sat ACP.
  8. The whole process starts again a buncch of times so ACP transferes its beta and omega c group from acetly coa to cys side then same steps 3-7 where we add 2 extra carbons every time we add malonyl coA.
  9. At the end the 1st FA is created which is palmitate (16C FA)

elongates from omega carbon to carbonlyl carbon

38
Q

What is the major saturated fatty acid synthesized de novo?

A

Palmitate

39
Q

Describe fatty acid elongation

How do we get it longer than 16 C

A

There are two fatty acid elongases, one in the mitochondria where it uses ACETYL-CoA to add 2C at a time. There is another in the ER and it uses MALONYL coA to elongate the FA. Note that we require NADPH. We extend the fatty acid by 2 carbons.

we use fatty acid elongase enzyme to lengthen chain.

40
Q

Explain adding double bonds to fa

this step is optional

A

Fatty acid desaturase is associated with the ER and is required to introduce db in fa. It is a multi-enzymic complex, and it has a source of “reducing equivalent: meaning that it used NADH to add H bonds (bc we lose a water) to go from saturated to monounsaturated (db).
In order for a saturated fatty acid to be a substrate for fa desaturase in must be in SCoA (sterol-CoA) form.

Note that cyanide sensitive factor (CSF) factor is the last acceptor for electrons donated by NADH.

We use fatty acid de-saturase. Note that this step is optional

41
Q

What is the major desaturase in mammalian systems?

A

Delta 9

inserts db b/w 9 and 10th C

42
Q

In mammalian fa desaturase system cannot insert double bond where?

A

Beyond the 9-10th positon of carbon. Becuase of this, linolenic and linoleic acids are essential fa meaning we must get from diet.

43
Q

If we do not get enough fatty acids, what diease can occur and explain it.

A

Essential fatty acid dificiency: lack of essential fatty acid uptake (linoleic acid, linolenic, arachidonic)
Metabolic characterists: incr concentration of mead acids to compensate for lack of essential fatty acids, scaly dermatitis and alopceia.

mead acid: 20:3delta5,8,11

44
Q

Why do we need polyunsat fa?

A

They contribute to the fluidity of the membrane

45
Q

Linoleic acid to arachidonic acod

A

18:2delta9,12–> 19:3delta6,9,12–>20:3delta8,11,15–>20:4delta5,8,11,14–> eicosanoids

linoleic acid–> desatu at 6th C–> elongate and every thing moves down by 2–> desatruate at 5th C=arachidonic acid–> eicosanoids

46
Q

What are the major organs synthesizing triglycerides?

A

Liver and adipose tissue

47
Q

What is the major storage form of fat?

A

Triglycerides (3 FA + GLYCEROL BACKBONE)

48
Q

How do we synthesize triglycerides?

A

We make glycerol phospate in the liver or adipose tissue. In the liver we can use glucose (glycolysis) or glycerol to make this. I. adipose tissue we can only use glucose (glycolysis).

We have our glycerol phosphate and acetyltransferase adds 1 fatty acid grp to make LPA. Acetylctranferase comes in again adn adds a 2nd FA group to make Phosphatiditc DAG. Phosphatase comes in and removes the phosphate grp to create DAG. This can act as a 2nd messenger or acetyl transferase can come in again, add a 3rd fa grp to make TRIAGLYCEROL (TAG).

49
Q

___ can funtion as an endocrone and secretory organ

A

Adipose tissue

50
Q

Fatty acids are synthesized under conditions of

A

of nutritional abundance, especially from carbohydrates (high Insulin/glucagons ratio)

51
Q

Fatty acids biosynthesis requires ____ which is provided primarily by the reactions catalyzed by malic enzyme and G6PDH and 6 phosphogluconate dehydrogenase.

A

NADPH

52
Q
  • Most fatty acids are stored in the form of
A

triacylglycerol

53
Q

Fatty acids may be elongated by enzymes associated with the

A

endoplasmic reticulum or the mitochondri

54
Q

Fatty acids are desaturated by enzymatic activities associated with the _____

A

endoplasmic retculum

55
Q

____ is a major regulation of hepatic lipogenesis.

A

ChREBP

56
Q

______ and ____are essential fatty acids. Mammalian Fatty Acid Desaturase cannot insert double bonds
beyond the _____position in the fatty acid

A

Linoleic Acid ,Linolenic Acid, 9-10

57
Q

What are our 7 lipogenic genes?

A
  1. Acetyl-CoA carboxylase
  2. Fatty acid synthase
  3. ATP citrate lyase
  4. Glucose-6-phosphate dehydrogenase
  5. 6-phosphoglucoronate dehydrogenase
  6. Malic enzyme
  7. Fatty acid desaturase

Biochem (17 decks)

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