Mtc Test 3: Lipid Metabolism

Front 1

What is the source of all carbons for fatty acids?

Back 1

acetyl CoA

Front 2

What is required for fatty acid synthesis?

Back 2

NADPH, ATP

Front 3

Where does fatty acid synthesis occur?

Back 3

cytosol

Front 4

Acetyl CoA is transported to the cytosol for fatty acid synthesis in the form of:

Back 4

citrate

Front 5

The ctirate-pyruvate shuttle generates what important cofactors:

Back 5

NAD+ required for glycolysis and NADPH required for fatty acid synthesis

Front 6

What is the rate limiting enzyme for fatty acid biosynthesis?

Back 6

Acetyl CoA carboxylase

Front 7

The activated intermediate for fatty acid synthesis is:

Back 7

malonyl CoA

Front 8

What is the cofactor for acetyl CoA carboxylase?

Back 8

biotin

Front 9

Malonyl CoA inhibits:

Back 9

entry of fatty acids into mitochondria; therefore, inhibits b-oxidation

Front 10

ACC-1 found in:

Back 10

cytosol of liver & adipose; produces malonyl CoA for fatty acid synthesis

Front 11

ACC-2 found in:

Back 11

mitochondrial membrane of muscle & liver; produces malonyl CoA for inhibition of B-oxidation in fed state; ensures these tissues primarily use glucose in fed state

Front 12

Fatty acid synthase

Back 12

- 2 identical subunits
- 7 catalytic sites
- catalyses all remaining reactions to convert malonyl groups to fatty acid

Front 13

Binding site for malonate on fatty acid synthase is:

Back 13

Phosphopantothenate group closely related to coenzyme A and comes from pantothenic acid

Front 14

1st step in fatty acid synthase reaction is:

Back 14

transfer of malonate from malonyl CoA to phosphopantotheinate on 1 subunit and acetyl group from acetyl CoA to cysteine residue on other subunit

Front 15

How many cycles of malonyl CoA addition to fatty acid ensues?

Back 15

7 cycles until 16-carbon acyl residue produced

Front 16

Final step in fatty acid synthesis is:

Back 16

hydrolysis to release chain as free palmitate

Front 17

Chain terminating process in fatty acid synthase dictated by:

Back 17

thiolase activity of 1 of domains of fatty acid synthase

Front 18

Fatty acids are modified by:

Back 18

elongating carbon chain & introducing double bonds

Front 19

What enzymes introduce double bonds into fatty acid residues?

Back 19

Desaturases

Front 20

Desaturases are very specific for:

Back 20

the position at which they introduce a double bond

Front 21

Desaturases require:

Back 21

COPPER

Front 22

What 4 steps are repeated in order for fatty acid biosynthesis?

Back 22

Condensation, reduction, dehydration, reduction

Front 23

Why are linoleic and linolenic fatty acids essential?

Back 23

We lack enzymes to introduce double bonds at the omega 3 and omega 6 positions

Front 24

What is a potential reason stearic acid doesn't raise cholesterol levels?

Back 24

It can be converted to unsaturated oleic aicd through remodeling

Front 25

Acetyl CoA carboxylase is activated at the cellular level (in cytosol) by:

Back 25

Citrate

Front 26

Acetyl CoA carboxylase is inhibited at the cellular level by:

Back 26

Palmitoyl CoA

Front 27

Activation of acetyl CoA carboxylase occurs when the enzyme is:

Back 27

Dephosphorylated

Front 28

Acetyl CoA carboxylase is activated at the whole body level by:

Back 28

Insulin

Front 29

Acetyl CoA carboxylase is inhibited at the whole body level by:

Back 29

Glucagon, Epinephrine

Front 30

Phosphorylation of acetyl CoA carboxylase occurs through activation of:

Back 30

cAMP-dependent protein kinase (PKA)

Front 31

Insulin dephosphorylates acetyl CoA carboxylase through action of:

Back 31

protein phosphatase

Front 32

What can partially activate acetyl CoA carboxylase even in absence of insulin?

Back 32

Citrate

Front 33

What can partially inactivate acetyl CoA carboxylase even in presence of insulin?

Back 33

Palmitoyl CoA

Front 34

How does lactate contribute to triglyceride overproduction associated with Type 2 diabetes?

Back 34

Lactate provides OAA & FAs the acetyl CoA needs for citrate formation; citrate can partially activate acetyl CoA carboxylase

Front 35

AMP-PK

Back 35

phosphorylates and inactivates acetyl CoA carboxylase

Front 36

AMP-PK is active when:

Back 36

AMP is high (fasting and exercise)
it decreases fatty acid synthesis and increases beta-oxidation

Front 37

AMP-PK is inactive when:

Back 37

glucose is high
- fed state and type 2 diabetes
- it increases fatty acid synthesis and decreases beta-oxidation

Front 38

What hormones, etc increase transcription of enzymes for fatty acid synthesis?

Back 38

Insulin, adipokines

Front 39

Why might unsaturated fats lower serum triglyceride levels?

Back 39

They seem to inhibit rate of transcription of enzymes associated with fatty acid synthesis.

Front 40

Transcription factor SREBP-1c upregulates the genes for which enzymes?

Back 40

Acetyl CoA carboxylase, fatty acid synthase, gly-3p acyltransferase

Front 41

How do fibrate drugs decrease the levels of enzymes associated with fatty acid synthesis?

Back 41

By activating PPAR alpha

Front 42

PPAR gamma controls:

Back 42

adipocyte differentiation, insulin sensitivity

Front 43

PPAR alpha:

Back 43

down-regulates fatty acid & TG synthesis, up-regulates B-oxidation

Front 44

What factors cause the liver to overproduce VLDL in Type 2 diabetes?

Back 44

Adipokines activate ACC-2; lactate produces OAA and acetyl CoA which are converted to citrate which also activates ACC-2

Front 45

Synthesis of triglycerides and compound lipids involves formation of:

Back 45

Phosphatidic acid

Front 46

Glycerol kinase

Back 46

converts glycerol to glycerol 3 phosphate in the liver

Front 47

In fed state, what intermediate is major source of 3 C backbone needed for triglyceride synthesis?

Back 47

DHAP

Front 48

In fasting state, hydrolysis of stored triglycerides in adipose results in:

Back 48

Release of glycerol

Front 49

Glyceroneogenesis

Back 49

Tissues convert glucose and amino acids to DHAP in fasting state; DHAP can be converted to glycerol-3-phosphate

Front 50

What enzyme is required for triglyceride formation?

Back 50

Glycerol 3-Pi acyl transferase

Front 51

Glycerol 3-Pi acyl transferase

Back 51

Catalyzes addition of fatty acids to glycerol 3-phosphate backbone

Front 52

Triglycerides can be formed from either:

Back 52

DHAP or glycerol phosphate

Front 53

Glycerol phosphate can be formed by either:

Back 53

Phosphorylation of glycerol (glycerol kinase); glyceroneogenesis in fasting state; reduction of DHAP in fed state

Front 54

Beta-oxidation occurs where?

Back 54

All tissues with mitochondria

Front 55

What are 2 stages of fatty acid oxidation?

Back 55

1. All carbons oxidized to acetyl CoA
2. Acetyl CoA oxidized by citric acid cycle

Front 56

How do hormones regulate HSL?

Back 56

Glucagon/epinephrine/glucocorticoids activate; insulin inhibits

Front 57

How are free fatty acids transported in blood?

Back 57

Bound to serum albumin

Front 58

What proteins appear to be regulated in parallel with hormone-sensitive lipase?

Back 58

Perilipin and adipose triglyceride lipase

Front 59

What protein does transport of fatty acids into the cell require?

Back 59

Fatty acid transport protein

Front 60

What enzyme catalyzes the formation of acyl CoA from free fatty acids?

Back 60

Acyl CoA synthetase

Front 61

What enzyme catalyzes formation of acyl carnitine on outer mitochondrial membrane?

Back 61

CPT-I

Front 62

What enzyme catalyzes formation of acyl CoA on matrix side of mitochondira?

Back 62

CPT-II

Front 63

What effect does exercise have on fatty acid oxidation?

Back 63

Increases CPT-I levels; Increases # of mitochondria

Front 64

What steps are involved in fatty acid oxidation?

Back 64

Oxidation, Hydration, Oxidation, Thiolysis

Front 65

Fatty acid oxidation produces:

Back 65

FADH2 and NADH

Front 66

Peroxisomes primarily perform oxidation on fatty acids of length:

Back 66

> C16; but definitely must be > 8

Front 67

Peroxisomes break down long chain fatty acids to:

Back 67

octanoyl CoA (C8) and acetyl CoA

Front 68

The first step in peroxisomal fatty acid oxidation utilizes what enzyme:

Back 68

acyl CoA oxidase

Front 69

Hormone-sensitive lipase hydrolyzes triglycerides to:

Back 69

free fatty acids and glycerol

Front 70

Malonyl Co-A inhibits:

Back 70

CPT-I

Front 71

What is the ultimate precursor for fatty acid synthesis?

Back 71

Citrate

Front 72

What drives beta-oxidation during fasting and starvation?

Back 72

mass action

Front 73

Levels of B-oxidation enzymes is regulated by:

Back 73

PPAR alpha

Front 74

PPAR alpha is activated by:

Back 74

omega 3 long chain polyunsaturated fatty acids

Front 75

PPAR alpha inactivated by:

Back 75

insulin (by way of MAPK) and glucose (by way of low AMP-PK levels)

Front 76

PPAR alpha increases levels of:

Back 76

fatty acid transport protein, acyl CoA synthetase, acyl CoA oxidase, CPT-I, other mitochondrial B-oxidation enzymes

Front 77

What is the mechanism of action of fibrate drugs?

Back 77

Activate PPAR alpha to stimulate B-oxidation

Front 78

What is the effect of exercise on PPAR alpha?

Back 78

Doubles PPAR alpha levels in muscle cells

Front 79

Where does ketone body synthesis occur?

Back 79

Exclusively in liver mitochondria

Front 80

Liver mitochondria have high concentrations of:

Back 80

HMG CoA synthase, HMG CoA lyase

Front 81

The primary keto-acid is:

Back 81

Acetoacetate

Front 82

Acetoacetate is reduced to:

Back 82

D3 hydroxybutyrate

Front 83

Where is acetoacetate:succinyl CoA transferase present?

Back 83

Mitochondria of all tissues except liver

Front 84

Thiolase

Back 84

cleaves acetoacetyl CoA to yield 2 molecules of acetyl CoA
- low in brain but induced by starvation

Front 85

Ability of mitochondria to use acetyl CoA limited by:

Back 85

Accumulation of NADH & ATP

Front 86

Acetyl CoA can't be used for fatty acid synthesis in fasting because:

Back 86

Acetyl CoA carboxylase inhibited by glucagon and fatty acyl CoA; this in turn forces acetyl CoA into the ketogenic pathway

Front 87

What causes acetyl CoA accumulation in type 1 diabetics?

Back 87

the enhanced gluconeogenesis depletes OAA and prevents acetyl CoA from re-entering citric acid cycle

Front 88

What is typical presentation of fatty acid oxidation disorder?

Back 88

infant or young child with lethargy & coma associated with fasting. HYPOKETONIC HYPOGLYCEMIA

Front 89

Presentation of CPT-II deficiency:

Back 89

Primarily involves muscle
Muscle weakness & exercise intolerance
Rhabdomyolysis following periods of intense exercise

Front 90

The presence of what in the urine can help in diagnosis of fatty acid oxidation disorders?

Back 90

The degradation products that accumulate in the urine

Front 91

What is the most common of the fatty acid oxidation enzyme defects?

Back 91

Defect in MCAD (medium chain acyl-CoA dehydrogenase)

Front 92

What is mechanism of hypoketonemia in fatty acid oxidation disorders?

Back 92

If can't oxidize fatty acids, can't produce precursors needed for ketone body production

Front 93

What is reason for hypoglycemia in fatty acid oxidation disorders?

Back 93

1. B-oxidation produces good deal of ATP needed for gluconeogenesis
2. body unable to use fatty acids or ketone bodies for energy so uses up a LOT of glucose

Front 94

Why does a defect in one dehydrogenase prevent oxidation of all fatty acids?

Back 94

Accumulation of fatty acyl CoA depletes cell of CoA and carnitine