Block 3 - Bsf: Fatty Acid Synthesis And Regulation

Front 1

What are the 2 main functions of fatty acid synthesis?

Back 1

To convert dietary carbohydrates and carbon skeletons of excess amino acids into TAG
(TAG can be stored until needed during fasting).

To produce a variety of fatty acids
(ex: components of complex lipids of biological membranes; precursors of eicosanoid lipid hormones)

Front 2

T/F

All animals store fat in white adipose tissue.

Back 2

False!

Most animals store fat in white adipose tissue. But, for example, sharks store fat in the liver.

Front 3

Brown adipose tissue in mammals uses fat mainly for what?

Back 3

Thermogenesis

It expresses mitochondrial uncoupling protein.

Front 4

What % of total body weigh is white adipose tissue in normal-weight adult humans?

Back 4

10-29%

Front 5

T/F

Both fatty acid synthesis and total capacity for fat storage are regulated.

Back 5

False!

Although fatty acids (FA) synthesis is regulated, the total capacity for fat storage is not.

Front 6

What 2 ways can fat mass increase in obesity?

Back 6

By the increase in the size of adipocytes and by the increase in the number of adipocytes.

Front 7

When are fatty acids (FAs) synthesized?

Back 7

When we have excess of calories in the diet

Front 8

Where does FA synthesis occur?

Back 8

Mainly in the liver, although FA are also synthesized in adipose tissue

Front 9

What is the major source of carbons for FA synthesis?

Back 9

Dietary carbohydrates

Front 10

Are carbohydrates the only source of carbons for FA synthesis?

Back 10

No, also amino acids and TCA cycle intermediates

Front 11

Name the fatty acid that is omega-6 fatty acid and 18:2 (9, 12).

Back 11

Linoleic acid

Front 12

Where are FAs with a chain length of 4-10 found?

Back 12

Milk

Front 13

There are at least how many carbons in structural lipids and TAGs?

Back 13

16

Front 14

Introduction of double bonds (increases/decreases) FA melting temperature.

Back 14

Decreases

Front 15

What 2 FAs are essential for humans?

Back 15

Linoleic acid and Linolenic acid

Front 16

What FA is the (omega-6) precursor of arachidonic (precursor of prostaglandins)?

Back 16

Linoleic acid

Front 17

What FA is the precursor of other omega-3 fatty acids?

Back 17

Linolenic acid

Front 18

What deficiency can result in decreased vision and altered learning behaviors?

Back 18

Linolenic deficiency

Front 19

What becomes essential if linoleic acid is deficient in the diet?

Back 19

Arachidonic acid

Front 20

What are the sources of fatty acids?

Back 20

Diet and synthesis de novo in the liver (lipogenesis)

Front 21

Fats are stored in ____________ as triglycerides and release through __________.

Back 21

adipose tissue, lipolysis

Front 22

T/F

Lipogenesis is critical for humans.

Back 22

False!

Lipogenesis is not critical for humans.
It is important in the development of obesity.

Front 23

(Lipogenesis/lipolysis) is inhibited in type 1 diabetes mellitus.

Back 23

Lipogenesis

Front 24

What provides carbons for FA synthesis?

Back 24

Malate shuttle

Front 25

T/F

FA synthesis is the reverse of beta-oxidation of FAs.

Back 25

False!

FA synthesis is
not reversal of b-oxidation of FA

Front 26

What is the 2 stage process of FA synthesis?

Back 26

synthesis of precursor → elongation

Front 27

Which enzyme catalyzes the committed step in FA synthesis?

Back 27

Acetyl-CoA carboxylase

Front 28

What does acetyl-CoA carboxylase synthesize?

Back 28

Malonyl-CoA

Front 29

What are the sources of fatty acids?

Back 29

Diet and synthesis de novo in the liver (lipogenesis)

Front 30

Fats are stored in ____________ as triglycerides and release through __________.

Back 30

adipose tissue, lipolysis

Front 31

T/F

Lipogenesis is critical for humans.

Back 31

False!

Lipogenesis is not critical for humans.
It is important in the development of obesity.

Front 32

(Lipogenesis/lipolysis) is inhibited in type 1 diabetes mellitus.

Back 32

Lipogenesis

Front 33

What provides carbons for FA synthesis?

Back 33

Malate shuttle

Front 34

T/F

FA synthesis is the reverse of beta-oxidation of FAs.

Back 34

False!

FA synthesis is
not reversal of b-oxidation of FA

Front 35

What is the 2 stage process of FA synthesis?

Back 35

synthesis of precursor → elongation

Front 36

Which enzyme catalyzes the committed step in FA synthesis?

Back 36

Acetyl-CoA carboxylase

Front 37

What does acetyl-CoA carboxylase synthesize?

Back 37

Malonyl-CoA

Front 38

What provides carbons for FA synthesis?

Back 38

Malate shuttle

Front 39

T/F

FA synthesis is the reverse of beta-oxidation of FAs.

Back 39

False!

FA synthesis is
not reversal of b-oxidation of FA

Front 40

What is the 2 stage process of FA synthesis?

Back 40

synthesis of precursor → elongation

Front 41

Which enzyme catalyzes the committed step in FA synthesis?

Back 41

Acetyl-CoA carboxylase

Front 42

What does acetyl-CoA carboxylase synthesize?

Back 42

Malonyl-CoA

Front 43

FA synthase is a multifunctional enzyme located where in the cell?

Back 43

Cytoplasm

Front 44

T/F

FA synthase is an acyl-carrier protein (ACP).

Back 44

True!

Front 45

Acetyl-CoA synthesis occurs in the ___________, while FA synthesis occurs in the _________.

Back 45

Mitochondria, cytoplasm

Front 46

Excess production of acetyl-CoA inhibits what enzyme?

Back 46

Pyruvate dehydrogenase

Front 47

Pyruvate carboxylase converts pyruvate to what?

Back 47

Oxaloacetate

Front 48

What two compounds are needed to make citrate in the mitochondria?

Back 48

Acetyl-CoA + oxaloacetate

Front 49

Where is the citrate transported to be converted back to acetyl-CoA and OAA?

Back 49

Cytosol

Front 50

Acetyl-CoA carboxylase is dependent on what?

Back 50

Biotin

Front 51

T/F

The conversion of acetyl-CoA to malonyl-CoA is ATP-driven.

Back 51

True!

Front 52

How do elevated levels of citrate affect acetyl-CoA carboxylase?
What type of regulation is this?

Back 52

Promotes aggregation → Activation

Allosteric regulation

Front 53

How do elevated levels of palmitoyl-CoA inhibit acetyl-CoA carboxylase?

What type of regulation is this?

Back 53

Inhibit (end product inhibition)

Allosteric regulation

Front 54

What hormone activates acetyl-CoA carboxylase?

Polymerization is promoted by (phosphorylation/dephosphorylation).

Back 54

Insulin

Dephosphorylation promotes polymerization

Front 55

How does phosphorylation affect acetyl-CoA carboxylase?

What type of regulation is this?

Back 55

Phosphorylation inhibits acetyl-CoA carboxylase and promotes dissociation.

Hormone-mediated regulation

Front 56

Which enzyme has an important role in tissues that do not significantly synthesize FAs?

What are a couple examples of these kinds of tissues?

Back 56

AMP-activated Kinase (AMPK)

Skeletal and cardiac muscles

Front 57

When AMP is high, AMPK ____________ acetyl-CoA carboxylase and ________ its activity.

Back 57

Phosphorylates, inhibits

Front 58

When AMP is high, production of what will be diminshed?
Therefore, what will be able to occur?

Back 58

Malonyl-CoA

Malonyl-CoA functions mainly as an inhibitor of fatty acid oxidation. Therefore, beta-oxidation of fatty acids can occur when malonyl-CoA is low.

Front 59

Low AMP levels will stimulate (increased/decreased) ATP production.

Back 59

Increased

Front 60

What 2 forms of long-term regulation increase or decrease expression of acetyl-CoA carboxylase?

Back 60

High carbohydrates/low-fat diet increases expression

Starvation or high fat/low carbohydrate diet decreases expression

Front 61

How many different enzymatic activities does the FA synthase monomer have?

Back 61

7

Front 62

Phosphopantetheine (Pant) is covalently linked to which domain of FA synthase?

Its long flexible arm allows it to do what?

Back 62

the ACP (acyl carrier protein) domain.

The long flexible arm of Pant allows it to move from one active site to another within the complex.

Front 63

The condensation stage of FA synthesis is catalyzed by which enzyme?

Back 63

FA synthase.

The acetyl group from acetyl CoA is transferred to ACP and then to the active site Cys of b-ketoacyl synthase
Malonyl group is transferred to ACP (1)
Beta-ketoacyl synthase catalyzes condensation of acyl and malonyl moieties (2)

Front 64

What are a couple of sources of NADPH?

Back 64

Pentose-P pathway and conversion of malate to pyruvate

Front 65

What is the major source of NADPH for FA synthesis?

Back 65

Pentose-P pathway

Front 66

How is the synthesis of FA synthase affected by a high carbohydrate/low fat diet?

Back 66

High rate of fatty acid synthesis

Front 67

How is the synthesis of FA synthase affected by fasting/starvation or a high fat diet?

Why?

Back 67

Low rate of fatty acid synthesis.

Because the high concentration of circulating fatty acids inhibits lipogenesis.

Front 68

What is the equation for FA synthesis?

Back 68

8 Ac-CoA + 7ATP + 14 NADPH + 14H+ → palmitate + 8 CoA + 6H2O + 7 ADP + 7Pi + 14 NADP+

Front 69

a) Complete oxidation of one molecule of palmitate yields _________ ATP
b) Complete oxidation of FA to CO2 and H2O yields _____ kcal/g
c) Carbohydrates and proteins yield only ____ kcal/g

Back 69

a) ~131 molecules
b) 9
c) 4

Front 70

During FA synthesis, the levels of malonyl CoA are (low/high).

Back 70

High

Front 71

What inhibits carnitine/palmitoyltransferase (CPTI)?

Back 71

Malonyl CoA

Front 72

What transports long-chain FAs into mitochondria for beta-oxidation?

Back 72

Carnitine/palmitoyltransferase (CPTI)

Front 73

What prevents oxidation of FAs during their synthesis?

Back 73

The high levels of malonyl-CoA during FA synthesis inhibit CPTI (thereby inhibiting the transport of long-chain FAs into the mitochondria for beta-oxidation).

Front 74

What are the short-term regulatory agents for acetyl-CoA carboxylase (Palmitate biosynthesis)?

Back 74

Citrate (allosteric activation)
C16-C18 acylCoAs (allosteric inhibition)
Insulin (stimulation)
Glucagon (inhibition)
cAMP and AMP-mediated phosphorylation (inhibition)
Dephosphorylation (stimulation)

Front 75

What are the long term (on the level of enzyme synthesis) regulatory agents of acetyl-CoA carboxylase (palmitate biosynthesis)?

Back 75

High-carbohydrate diet (stimulation)
Fat-free diet (stimulation)
High fat diet/PUFAs (inhibition)
Fasting (inhibition)
Glucagon (inhibition)

Front 76

What are the regulatory agents of FA synthase?

Which of these are on the level of enzyme synthesis?

Back 76

Phosphorylated sugars (allosteric activation)
High-carbohydrate diet (stimulation)
Fat-free diet (stimulation)
High-fat diet/PUFAs (inhibition)
Fasting (inhibition)
Glucagon (inhibition)

All but phosphorylated sugars regulate on the level of enzyme synthesis.

Front 77

Where does FA elongation occur?

Back 77

In the endoplasmic reticulum (ER) and mitochondria.

These organelles use separate enzymatic processes.

Front 78

Palmitoyl-CoA is a substrate for what enzyme?

Back 78

Fatty acid elongase (FAE)

Palmitoyl-CoA + malonyl-CoA -> stearoyl-CoA

Front 79

Brain tissue can produce FAs up to how many carbons?

Back 79

24 carbons.

These very long FAs are required for synthesis of brain lipids.

Front 80

Where does the desaturation of FAs occur?

Back 80

In the ER

Front 81

What process is catalyzed by mixed-function oxidases and requires NADPH and O2?

Back 81

Desaturation of FAs

Palmitic (C16:0) → palmitoleic acid (C16:1, D9)

Front 82

T/F

Humans have the ability to introduce double bond from carbon 10 to the w-end of the chain.

Back 82

False!

Humans lack ability to introduce double bond from carbon 10 to the w-end of the chain

Front 83

For desaturation of FAs, what must you have in the diet?

Back 83

Must have polyunsaturated linoleic and linolenic acids in the diet

Front 84

How are triacylglycerols (TAGs) formed?

Back 84

By FA esterification → loss of charge and formation of neutral fat

Front 85

TAGs that are solid at room temp are what?

Back 85

Fats

Front 86

TAGs that are liquid at room temp are what?

Back 86

Oils

Front 87

T/F

TAGs usually contain FAs of the same type.

Back 87

False!

TAGs usually contain FAs not of the same type.

Front 88

Whatis the initial acceptor of FA during TG (triglyceride) synthesis?

Back 88

Glycerol phosphate (GP)

Front 89

Where are the two pathways for GP production?

Back 89

In the liver and adipose tissue

Front 90

In both the liver and adipose tissue, what can GP be produced from?

Back 90

Glucose

glycolysis → dihydroxyacetone-P (DHAP) → glycerol-P

Front 91

In the liver only, what can GP be produced from?

Back 91

glycerol → GP (adipocytes lack glycerol kinase)

Front 92

FA must be converted to its activated form to participate in TG synthesis.
The reaction is catalyzed by what?

Back 92

The family of fatty acyl-CoA synthetases

Front 93

What reactions are involved in the synthesis of TG from GP and fatty acyl-CoA?

Back 93

Sequential addition of two FAs from fatty acyl CoA
Removal of phosphate
Addition of third FA

Front 94

After a meal, adipocytes synthesize what and secrete it into the capillary of adipose in response to (low/elevated) insulin/glucagon ratio.

Back 94

Lipoprotein lipase (LPL)

Elevated

Front 95

After a meal, what does LPL digest?

Back 95

TG of chylomicrons and VLDL forming free FA

Front 96

Free FAs that enter adipocytes are ______ and converted to _______.

Back 96

Active, TGs

Front 97

Insulin stimulates glucose metabolism and its conversion to ______ in ________.

Back 97

FAs, adipocytes

Front 98

During fasting, the low insulin/glucagon ratio increases the synthesis of _______ in adipocytes, stimulating _________.

Back 98

cAMP, lipolysis

Front 99

During fasting high cAMP activates _______, which, in turn, phosphorylates _________________.

Back 99

PKA, hormone-sensitive lipase

Front 100

After a meal, what does LPL digest?

Back 100

TG of chylomicrons and VLDL forming free FA

Front 101

Free FAs that enter adipocytes are ______ and converted to _______.

Back 101

Active, TGs

Front 102

Insulin stimulates glucose metabolism and its conversion to ______ in ________.

Back 102

FAs, adipocytes

Front 103

During fasting, the low insulin/glucagon ratio increases the synthesis of _______ in adipocytes, stimulating _________.

Back 103

cAMP, lipolysis

Front 104

During fasting high cAMP activates _______, which, in turn, phosphorylates _________________.

Back 104

PKA, hormone-sensitive lipase

Front 105

What cleaves a FA from TG?

Back 105

Lipase

Front 106

Other lipases complete the lipolysis and FAs and glycerol are released into the ______.

Back 106

Blood

Front 107

In what mechanism are FAs used to resynthesize TG to limit FAs release into circulation?

Back 107

Glyceroneogenesis

Front 108

Resynthesis of TG in glyceroneogenesis depends on an adequate supply of what?

Back 108

Glycerol 3-phosphate (G3P)

Front 109

What is G3P produced from in adipocytes?

Back 109

G3P is produced from carbons of lactate, pyruvate or AAs

Front 110

What is the key enzyme in glyceroneogenesis?

Back 110

(PEPCK) Phosphoenolpyruvate carboxykinase

Front 111

PEPCK is induced by (low/elevated) [cAMP] in response to glucagon and epinephrine

Back 111

Elevated

Front 112

In glyceroneogenesis...

PEPCK converts a)______ to PEP.
PEP is converted to b)_______ through gluconeogenesis.
DHAP is reduced to c)______ and used to re-esterify FAs before they leave the adipocyte, thus modulating d)________________ by adipose tissue

Back 112

a) OAA
b) DHAP
c) G3P
d) Free FA release

Front 113

Can released glycerol be metabolized in adipocytes?

Why/why not?

Back 113

No, because there isn't any glycerol kinase

Front 114

Where is glycerol transported to to be phosphorylated?

Back 114

The liver

Front 115

Freed FAs are released into plasma and transported to the tissues in complex with what transporter?

Back 115

Albumin

Front 116

What tissues cannot use plasma FAs?

Back 116

Erythrocytes and the brain

Front 117

What lipids are componenets of blood lipoproteins, bile and lung surfactant?

Back 117

Glycerophospholipids

Front 118

What lipids are the source of polyunsaturated FAs (arachidonic acid)?

Back 118

Glycerophospholipids

Front 119

What lipids are components of myelin sheath in CNS?

Back 119

Sphingolipids

Front 120

What lipids serve in intercellular communication and antigens of ABO blood groups?

Back 120

Sphingolipids

Front 121

Two different mechanisms are used to add head group to phosphatidic acid:

a)_________ is removed to produce DAG. DAG reacts with activated head group, which is produced by addition of b)_____.

Phosphatidic acid reacts with c)________ to form d)__________. (d) reacts with head group.

Back 121

a) Phosphate
b) CDP
c) CTP
d) CDP-DAG

Front 122

What does DAG react with to produce phosphatidylethanolamine (PEA)?

Back 122

CDP-Ethanolamine

Front 123

What does DAG react with to produce phosphatidylcholine (PC)?

Back 123

CDP choline

Front 124

What type of reaction converts PEA to PC?

Back 124

Methylation reaction

Front 125

What type of reaction converts PEA to Phosphatidylserine (PS)?

Back 125

Exchange reaction

Front 126

What type of reaction converts PS to PEA?

Back 126

Decarboxylation reaction

Front 127

CDP-DAG reacts with phosphatidylglycerol to form what?

Back 127

Cardiolipin

Front 128

What is cardiolipin a component of?

Back 128

the mitochondrial membrane

Front 129

CDP-DAG reacts with inositol to form what?

Back 129

Phosphatidylinositol (PI)

Front 130

How can phosphatidylinositol (PI) be converted to PIP2?

Back 130

Phosphorylation

Front 131

What second mesengers is PIP2 a source of?

Back 131

DAG and IP3

Front 132

What type of lipid is plasmalogen?

Back 132

Plasmalogen is an ether glycerolipid

Front 133

Plasmalogen is produced from DHAP in the following steps:

Fatty acyl CoA reacts with DHAP forming a)_______. Ether linkage is formed through exchange of b)_________ group for c)_________. Formation of d____________ between carbons 1 and 2 of alkyl group produces a plasmalogen

Back 133

a) ester
b) fatty acyl
c) fatty alcohol
d) double bond

Front 134

Where is ethanolamine plasmalogen found?

Back 134

Myelin

Front 135

Where is choline plasmalogen found?

Back 135

Heart muscle

Front 136

Where does plasmalogen synthesis occur?

Back 136

Peroxisomes

Front 137

What is affected in individuals with Zellweger syndrome?

Back 137

Synthesis of plasmalogen

Front 138

The respiratory distress syndrome (RDS) of premature infants is related to a deficiency in what?

Back 138

Lung surfactant (phosphatidylcholine)

Front 139

T/F

RDS is a major cause of death in newborns.

Back 139

True!

Front 140

Is RDS preventable?

Back 140

Yes - RDS is preventable if prematurity can be avoided.

Front 141

What produces and secretes phosphatidylcholine?

Back 141

Granular pneumocytes

Front 142

What is the major component of lung surfactant that prevents alveolar collapse (atelectasis)?

Back 142

Phosphatidylcholine

Front 143

T/F

RDS can occur in adults.

Back 143

True!

RDS can occur in adults whose surfactant-producing pneumocytes are damaged or destroyed.

Front 144

What is Phospholipase C activated by?

Back 144

Hormonal stimuli

Front 145

What enzyme produces second messengers DAG and IP3 from PIP2?

Back 145

Phospholipase C

Front 146

What activates phospholipase A2?

Back 146

Signals for the
synthesis of eicosanoids

Front 147

What enzyme is involved in repair of membrane lipids damaged by oxidative free-radical reactions?

Back 147

Phospholipase A2

Front 148

What is the only sphingosine-based phospholipid?

Back 148

Sphingomyelin

Front 149

What phospholipid is synthesized by the reaction of ceramide with phosphatidylcholine?

Back 149

Sphingomyelin

Front 150

Sphingolipids are degraded by what?

Back 150

Lysosomal enzymes

Front 151

Neimann- Pick disease is caused by a deficiency in what enzyme?

Back 151

Sphingomyelinase

(No man PICKs his nose with his SPHINGer! - Thanks Bondarenko!)

Front 152

Obesity has been shown to predispose people to what diseases?

Which one is 80% associated with obesity?

Back 152

Diabetes mellitus type 2, coronary heart diseases, hypertension, stroke, arthritis, and cancer.

Diabetes mellitus 2 is 80% associated.

Front 153

What are the BMI ranges?

Back 153

BMI less than 18.5kg/m2 = underweight
BMI of 18.5 - 24.9kg/m2 = normal weight
BMI 25-30kg/m2 = overweight or grade I obesity
BMI >30kg/m2 = clinical or grade II obesity
BMI > 40kg/m2 = morbid or grade III obesity

Front 154

What is the amount of leptin in the blood proportional to?

Back 154

Body fat content

Front 155

What hormone suppresses appetite (sensation of satiety), promotes lipolysis, and inhibits FA synthesis?

Back 155

Leptin

Front 156

Animals deficient in a)________ are obese and have low sensitivity to b)_________.

Back 156

a) Leptin
b) Insulin

Front 157

What does leptin treatment lead to?

Back 157

Increased FAs oxidation and improved sensitivity to insulin

Front 158

What hormone can accelerate puberty and correct sterility in mice?

On the other hand, what can delay puberty?

Back 158

Leptin

Undernutrition

Front 159

What is the major hormone produced by adipocytes?

Back 159

Adiponectin

Front 160

Adiponection production and release is reduced when adipocytes become (smaller/larger).

Back 160

Larger

Front 161

What does adiponectin activate?

Back 161

AMP-activated protein kinase (AMPK) and nuclear transcription factor

Front 162

Activation of AMPK leads to what effects in the muscle, liver, and blood?

Back 162

Enhanced FA oxidation and glucose uptake by the muscle
Enhanced FA oxidation in the liver
Reduced blood glucose levels and free FAs

Front 163

T/F

The more obese the person is, the more difficult it is for circulating FAs and glucose to be used by other tissues.

Back 163

True!