Fatty Acid Synthesis & Regulation

Front 1

Name some obesity-related diseases

Back 1

Diabetes
Hypertension
Cardiovascular
Cancer

Front 2

What are functions of fatty acid synthesis?

Back 2

1. To convert dietary cabohydrates and carbon skeletons of excess amino acids into triacyglycerols (TAG). TAG can be stored until needed during fasting.
2. To produce a variety of fatty acids.
They are components of complex lipids of biological membranes.
They are also precursors of eicosanoid hormones.

Front 3

Where do most animals store fat?

Back 3

White adipose tissue

Front 4

Where do sharks store fat?

Back 4

In the liver

Front 5

What is the importance of brown adipose tissue?

Back 5

It utilizes fat mainly for thermogenesis.
It expresses mitochondrial uncoupling protein.

Front 6

What is the largest organ in the body?

Back 6

White adipose tissue.
In normal-weight adult humans white adipose tissue represents 10-29% of total body weight.

Front 7

Is the total capacity for fat storage regulated?

Back 7

NO.
BUT fatty acid synthesis is regulated.

Front 8

How does fat mass increase obesity? (Two ways)

Back 8

1. By the increase in the size of adipocytes.
2. By the increase in the number of adipocytes.

Front 9

When are fatty acids synthesized?

Back 9

When there is an excess of calories in the diet.

Front 10

Where does FA synthesis occur?

Back 10

Mainly in the LIVER, but FA are also synthesized in adipose tissue.

Front 11

What is the major source of carbons for FA synthesis?

Back 11

Dietary carbohydrates.

Front 12

Are carbohydrates the only source of carbonds for FA synthesis?

Back 12

NO.
Amino acids and TCA cycle intermediates are also sources of carbons.

Front 13

What do descriptions of FA include?

Back 13

1. The number of carbon atoms
2. The double bonds in them

Front 14

How do you tell where the double bond is located? (two different ways)

Back 14

1. Counting carbons from the carboxyl end OR
2. Counting carbons from the methyl- or w (omega) end.

Front 15

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

Back 15

In milk

Front 16

How many fatty acid carbons do structural lipids and triacyglycerols contain?

Back 16

At least 16 carbons.

Front 17

How does the introduction of double bonds affect the FA melting temperature?

Back 17

It DECREASES the FA melting temperature.
NOTE: this is why unsaturated fatty acids are liquid at room temperature (i.e. oils)

Front 18

Which fatty acids are essential for humans (there are 2)

Back 18

1. Linoleic acid (w-6)- precursor of arachidonic acid.
2. Linolenic acid- precursor of other w-3 fatty acids.

Front 19

What does a linolenic acid deficiency lead to?

Back 19

Decreased vision and altered learning behaviors.

Front 20

What happens if linoleic acid is deficient in the diet?

Back 20

Arachidonic acid becomes essential.

Front 21

Arachidonic acid is a precursor of ________?

Back 21

Prostaglandins

Front 22

Name the three major source of fatty acids

Back 22

1. Diet
2. Lipogenesis (de novo synthesis in the liver)
3. Lipolysis (fats are stored in adipose tissue as triglycerides and released through lipolysis)

Front 23

Is lipogenesis activated or inhibited in type 1 diabetes?

Back 23

Inhibited

Front 24

The _______ shuttle provides carbons for FA synthesis

Back 24

Malate

Front 25

Name the two stages and two enzymes involved in FA synthesis

Back 25

1. Synthesis of precursor (malanoyl-CoA)
Enzyme: Acetyl-CoA carboxylase
Note- this is the committed step.
2. Elongation
Enzyme: FA synthase

Front 26

Explain the Malate shuttle

Back 26

1. Acetyl-CoA synthesis is in mitochondria.
2. FA synthesis is in the cytoplasm
3. Excess production of acetyl-CoA --> inhibition of pyruvate dehydrogenase
4. Pyruvate carboxylase converts pyruvate to oxaloacetate (OAA)
5. Acetyl-CoA + OAA= citrate
6. The citrate is transported to the cytosol and converted back to acetyl-CoA and OAA.

Front 27

What is the committed step in FA synthesis?

Back 27

The synthesis of Malonyl-CoA.
It is catalyzed by Acetyl-CoA carboxylase- a Biotin-dependent enzyme (ATP-driven reaction).

Front 28

Name the two major types of regulation of Acetyl-CoA Carboxylase

Back 28

1. Allosteric regulation
2. Hormone-mediated regulation

Front 29

Describe allosteric regulation of Acetyl-CoA Carboxylase.

Back 29

1. Elevated levels of citrate promotes aggregation-> Activation
2. Elevated leveles of palmitoyl-CoA inhibit the enxyme (end product inhibition)

Front 30

Describe hormone-mediated regulation of Acetyl-CoA Carboxylase.

Back 30

1. Insulin activates acetyl-CoA carboxylase.
Dephosphorylation promotes polymerization.
2. Phosphorylation inhibits acetyl-CoA carboxylase.
Phosphorylation promotes dissociation.

Front 31

Where does AMP-activated Kinase (AMPK) have an important role?

Back 31

In tissues that do not significantly synthesize FAs:
1. Skeletal muscle
2. Cardiac muscle

Front 32

What is the role of AMP-activated Kinase (AMPK) when AMP is high.

Back 32

1.AMPK phosphorylates acetyl-CoA carboxylase and inhibits its activity.
2. Malonyl-CoA production is diminished, releasing FA oxidation from inhibition (malonyl-CoA is an inhibitor of fatty acid oxidation)
3. This will lead to increased ATP production

Front 33

Describe long-term regulation of Acetyl-CoA Carboxylase (two ways)

Back 33

1. High carbohydrate/low fat diet INCREASES expression
2. Low carbohydrate/ high fat diet DECREASES expression

Front 34

_______ is a multifunctional dimeric enzyme. Its monomer has 7 different enzymatic activities, and it contains an acyl carrier protein (ACP) domain.

Back 34

Fatty Acid Synthase

Front 35

What is covalently linked to the acyl carrier protein domain of fatty acid synthase?

Back 35

Phosphopantetheine.(pant).

Front 36

What feature of Phosphopantetheine allows it to move from one active site to another within the complex?

Back 36

The long flexible arm

Front 37

Describe the condensation stage of FA synthesis (3 steps)

Back 37

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

Front 38

What are the two sources of NADPH for FA synthesis?

Back 38

1. Pentose phosphate pathway is the MAJOR source of NADPH.
2. Conversion of malate to pyruvate also produces cystolic NADPH

Front 39

Describe the effects of nutrition on fatty acid synthesis.

Back 39

* High carbohydrate/low fat diet= high rate of fatty acid synthesis
* Fasting/starvation or high fat diet=low rate of fatty acid synthesis.
NOTE: high concentration of circulating fatty acids inhibits lipogenesis.

Front 40

How many molecules of ATP does complete oxidation of one molecule of palmitate yield?

Back 40

131 molecules of ATP

Front 41

How many calories does complete oxidation of fatty acid to CO2 and H2O yield?

Back 41

9 kcal/g

Front 42

How many calories do carbohydrates and proteins yield?

Back 42

4 kcal/g

Front 43

How does Malonyl CoA inhibit fatty acid oxidation?

Back 43

1. During FA synthesis, levels of malonyl CoA is high
2. Malonyl CoA inhibits carnitine palmitoyltransferase (CPTI)
3. CPT1 transport long-chain FAs into mitochondria for B-Oxidation
4. Malanoyl CoA prevents oxidation of FAs during their synthesis.

Front 44

Where does fatty acid elongation occur?

Back 44

In the endoplasmic reticulum and mitochondria.
NOTE: these organelles use separate enzymatic processes

Front 45

What is a substrate for fatty acid elongase (FAE)

Back 45

Palmitoyl-CoA
Palmitoyl-CoA + malonylCoA -> stearoyl-CoA

Front 46

What length FAs (e.g. medium chain, long chain etc)are required for the synthesis of brain lipids?

Back 46

Very long chain FAs.
Brain tissue can produce FAs up to 24-C

Front 47

Where does desaturation of fatty acids occur?

Back 47

In the Endoplasmic Reticulum

Front 48

What catalyzes the desaturation of fatty acids?

Back 48

Mixed-function oxidases.
This reaction requires NADPH and O2
Palmitic (C16:0) → palmitoleic acid (C16:1, D9)

Front 49

Are humans able to introduce double bond from carbon 10 to the w-end of the chain?

Back 49

NO

Front 50

How are triacylglycerols formed?

Back 50

By fatty acid esterification-> loss of charge and formation of neutral fat

Front 51

Are fats solid or liquid at room temperature.

Back 51

Solid

Front 52

Are oils solid or liquid at room temperature?

Back 52

Liquid

Front 53

Do Triacylglycerols (TAGs)contain FA of the same type?

Back 53

NO.
TAGs usually contain FAs NOT of te same type.

Front 54

How are triacylglycerols stored?

Back 54

As droplets in adipocytes.

Front 55

What is the initial acceptor of fatty acids during triacylglycerol synthesis?

Back 55

Glycerol Phosphate (GP)

Front 56

What are the two pathways for glycerol phosphate (GP) production?

Back 56

1. In the liver and adipose tissue: GP can be produced from glucose: : glycolysis → dihydroxyacetone-P (DHAP) → glycerol-P
2. In the liver ONLY: glycerol → GP (adipocytes lack glycerol kinase)

Front 57

What catalyzes the conversion of FA to its activated form?

Back 57

Fatty acyl-CoA synthetases.
NOTE: FA must be converted to its activated form to participate in triacylglycerol synthesis

Front 58

Synthesis of triacylglycerol from glycerol phosphate and fatty acyl-CoA involves four reactions. What are they?

Back 58

1 & 2. Sequential addition of two FAs from fatty acyl CoA
3. Removal of phosphate
4. Addition of a 3rd FA

Front 59

Describe the synthesis of Triacylglycerol (TG) in Adipose tissue.

Back 59

1. After a meal, the TG stores in adipose tissue increase
2. Adipocytes synthesize lipoprotein lipase (LPL) and secrete it into the capillary of adipose in response to elevated insulin/glucagon ratio
3. LPL digests TG of chylomicrons and VLDL forming free FA
4. Free FAs that enter adipocytes are activated and converted to TGs

Front 60

What is the effect of insulin on glucose metabolism and its conversion to FAs in adipocytes?

Back 60

Insulin stimulates glucose metabolism and its conversion to FAs in adipocytes

Front 61

Describe the release of fatty acids from triacylglycerol (TG)

Back 61

1. During fasting, the decrease low insulin/glucagon ratio increases the synthesis of cAMP in adipocytes, stimulating lipolysis
2. High cAMP activates PKA, which, in turn, phosphorylates hormone-sensitive lipase
3. Lipase cleaves a FA from TG
4. Other lipases complete the lipolysis and FAs and glycerol are released into blood
5. FAs are oxidized in the of muscle and other tissues to produce energy

Front 62

Why are fatty acids used to resynthesize triacylglycerol?

Back 62

To limit fatty acid release into circulation

Front 63

What does resynthesis of triacylglycerol depend on?

Back 63

Adequate supply of glycerol-3-phosphate.

Front 64

Glycerol-3-phosphate is produced from carbons of, _____, _______, or ______ in adipocytes.

Back 64

Lactate, pyruvate, or amino acids.

Front 65

What is the key enzyme involved in the resynthesis of triacylglycerol?

Back 65

(PEPCK) Phosphoenolpyruvate carboxykinase is the key enzyme

Front 66

Describe the mechanism of Phosphoenolpyruvate carboxykinase (PEPCK)

Back 66

1. PEPCK is Induced by elevated [cAMP] in response to glucagon and epinephrin
2. PEPCK converts OAA to phosphoenolpyruvate (PEP)
3. PEP is converted to DHAP through gluconeogenesis
4. DHAP is reduced to G3P and used to re-esterify FAs before they leave the adipocyte, thus modulating free FA release by adipose tissue

Front 67

Can released glycerol be metabolized in adipocytes?

Back 67

NO because adipocytes lack glycerol kinase.

Front 68

Can plasma FAs be used by erythrocytes and the brain?

Back 68

NO

Front 69

Glycerol is transported to the ______ where it is _________

Back 69

Liver, phosphorylated

Front 70

Freed FAs are released into plasma and transported to the tissues in complex with _______

Back 70

Albumin

Front 71

________ are:
1. Components of blood lipoproteins, bile, and lung surfactant.
2. The source polyunsaturated FAs (arachidonic acid)

Back 71

Glycerophospholipids

Front 72

________ :
1. Components of myelin sheath in CNS
2. Serve in intercellular communication and antigens of ABO blood groups

Back 72

Sphingolipids

Front 73

Describe the two mechanisms involved in the syntheis of glycerophospholipids.

Back 73

1. Phosphate is removed to produce Diacylglycerol (DAG)
DAG reacts with activated head group, which is produced by addition of CDP
2. Phosphatidic acid reacts with CTP to form CDP-GAD
CDP-DAG react with head group
NOTE: these mechanisms are used to add head group to phosphatidic acid

Front 74

Name the two ways phosphatidylethanolamine (PEA) can be synthesized.

Back 74

1. DAG reacts with CDP-Ethanolamine to produce phosphatidylethanolamine
2. Phosphatidylserine can be converted to PEA by decarboxylation reaction

Front 75

Name the two ways phosphatidylcholine can be synthesized.

Back 75

1. DAG reacts with CDP choline to produce phosphatidylcholine (PC)
2. Phosphatidylethanolamine (PEA) can be converted to PC by amination reaction

Front 76

How is Phosphatidylserine formed?

Back 76

Phosphatidylethanolamine (PEA) can be converted to Phosphatidylserine (PS) by exchange reaction

Front 77

How is cardiolipin formed?

Back 77

CDP-DAG reacts with phosphatidylglycerol to form cardiolipin (component of the mitochondrial membrane)

Front 78

How is phosphatidylinositol (PI) formed?

Back 78

CDP-DAG reacts with inositol to form phosphatidylinositol (PI)

Front 79

How is PIP2 formed?

Back 79

By the phosphorylation of phosphatidylinositol. PIP2 is a source of second mesengers: DAG and IP3.

Front 80

Describe the synthesis of plasmalogen.

Back 80

1. Plasmalogen is produced from DHAP.
2. Fatty acyl CoA reacts with DHAP forming ester
3. Ether linkage is formed through exchange of fatty acyl group for fatty alcohol
4. Formation of double bond between carbons 1 and 2 of alkyl group produces a plasmalogen

Front 81

Where is Ethanolamine plasmalogen found?

Back 81

In myelin

Front 82

Where is Choline plasmalogen found?

Back 82

In heart muscle

Front 83

Where does plasmalogen synthesis occur?

Back 83

In peroxisomes.
Affected in individuals with Zellweger syndrome

Front 84

What causes respiratory distress syndrome?

Back 84

1. The respiratory distress syndrome (RDS) of a premature infants is related to a deficiency in the synthesis of a substance known as lung surfactant (phosphatidylcholine)
2. The premature infant does not produce adequate amounts of lung surfactant
3. RDS is a major cause of death in the newborn
4. RDS is preventable if prematurity can be avoided

Front 85

Phosphatidylcholine is produced and secreted by _________?

Back 85

Granular pneumocytes.
*It is the major component of lung surfactant that prevents alveolar collapse (atelectasis)
* Respiratory distress syndrome (RDS) can occur in adults whose surfactant-producing pneumocytes are damaged or destroyed

Front 86

Describe the degradation of glycerophospholipids by Phospholipase C

Back 86

1. Activated by hormonal stimuli
2. Produces second messengers DAG and IP3 from PIP2

Front 87

Describe the degradation of glycerophospholipids by Phospholipase A2

Back 87

1. Activated by the signals for the synthesis of eicosanoids
2. In repair of membrane lipids damaged by oxidative free-radical reactions

Front 88

What are the three major functions of sphingolipids?

Back 88

1. Intercellular communication
2. Antigenic determinant of ABO blood groups
3. Sphingomyelin is a component of the myelin sheath (it's the only sphingosine-based phospholipid)

Front 89

How is sphingomyelin synthesized?

Back 89

By the reaction of ceramide with phosphatidylcholine.

Front 90

How are sphingolipids degraded?

Back 90

By lysosomal enzymes

Front 91

Deficiency of sphingomyelinase results in _______ disease?

Back 91

Niemann-Pick

Front 92

Describe Niemann-Pick disease.
1. Metabolite accumulated
2. Symptoms

Back 92

1. Sphingomyelin
2. Hepatosplenomegaly & Neurodegenerative course (Type A)

Front 93

Obesity predisposes to several diseases. Name 6 of them.

Back 93

1. Diabetes mellitus type 2 (80% associated with obesity)
2. Coronary heart diseases
3. Hypertension
4. Stroke
5. Arthritis
6. Cancer

Front 94

Obesity developed from the interaction of _______ and ______

Back 94

Individual biology and the environment.

Front 95

________ is a condition when fatty tissue is increased to a point where it is a risk factor for certain health conditions or increased mortality

Back 95

Obesity

Front 96

What is the formula for Body mass index (BMI)?

Back 96

BMI= weight (kg)/(height [m])2

Front 97

BMI less than 18.5kg/m2 is considered ____________

Back 97

Underweight

Front 98

BMI of 18.5 - 24.9kg/m2 is considered ______________

Back 98

Normal weight

Front 99

BMI 25-30kg/m2 is considered _____________

Back 99

Overweight or grade 1 obesity

Front 100

BMI >30kg/m2 is considered

Back 100

Clinical or grade 2 obesity

Front 101

BMI > 40kg/m2 is considered

Back 101

Morbid or grade 3 obesity

Front 102

Name the two major hormone-like substances adipose tissue produces

Back 102

1. Leptin
2. Adiponectin

Front 103

What is the relationship of the amount of leptin in the blood to the body fat content?

Back 103

Amount of leptin in blood is proportional to the body fat content

Front 104

What are the effects of Leptin (3 major)

Back 104

1. Suppresses appetite (sensation of satiety)
2. Promotes lipolysis
3. Inhibits FA synthesis

Front 105

What is the effect of leptin on puberty and sterility in mice?

Back 105

Leptin can accelerate puberty and correct sterility in mice

NOTE: undernutrition can delay puberty

Front 106

What is the effect of leptin deficiency in animals?

Back 106

Animals deficient in leptin are obese and have low sensitivity to insulin

Front 107

What are the effects of leptin treatment?

Back 107

Leptin treatment leads to increased FAs oxidation and improves sensitivity to insulin

Front 108

What is the MAJOR hormone produced by adipocytes?

Back 108

Adiponectin

Front 109

What effect does Adiponectin have on AMP-activated protein kinase (AMPK) and nuclear transcription factor?

Back 109

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

Front 110

What are the effects of AMP-activated protein kinase AMPK) activation? 3 effects

Back 110

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

Front 111

What occurs when adipocytes increase in size?

Back 111

1. Less adiponectin is released by adipose tissues
2. The more obese the person is, the more difficult for circulating Fas and glucose to be used by other tissues