Quiz 1 Lipid Metabolism

Question 1

Degradation of fatty acids is termed ____.

Answer 1

Beta oxidation

Question 2

The major source of carbon for fatty acid synthesis is __.

A. Fats
B. Carbohydrates
C. Protesin

Answer 2

B. Dietary carbohydrates are the majors source of carbon for fatty acid synthesis

Question 3

Fatty acid synthesis primarily occurs in the ___.

Answer 3

Liver

*also in adipose tissue, brain, kidneys, and lactating mammary glands

Question 4

The end product of fatty acid synthesis is ___.

Answer 4

Palmitic Acid = 16 carbon molecule

Question 5

The precursor of Fatty Acid synthesis is ___.

Answer 5

Acetyl-CoA

Question 6

Acetyl-CoA is made in the ___ but needed in the ___ for Fatty Acid synthesis.

Answer 6

Mitochondria / cytoplasm

Question 7

Acetyl-CoA is ___ to form ___ during the rate limiting step of Fatty Acid synthesis.

Answer 7

Carboxylated / Malonyl-CoA

Question 8

How is Acetyl-CoA transported out of the mitochondria?

Answer 8

Acetyl-CoA is converted to Citrate by Citrate Synthase

—>Citrate can exit the mitochondria via a Citrate shuttle

—>Citrate outside the mitochondria can be reconverted to Acetyl-CoA by ATP Citrate Lyase

• Citrate splits into Acetyl-CoA and OAA
• OAA is a precursor for pyruvate and will be re-uptaken into the mitochondria

Question 9

Regulation of Citrate Lyase:

Answer 9

Activators: Glucose / Insulin
*signals body of FED state and the need for glucose storage

Inhibition: PUFA / Leptin
*signals HUNGRY state and the need for glucose release (therefore, inhibition of glucose storage)

Question 10

Conversion of Acetyl-CoA to Malonyl-CoA by ___ is the rate limiting step of Fatty Acid synthesis.

Answer 10

Acetyl-CoA Carboxylase

Question 11

Acetyl CoA Carboxylases uses ___ and ___ as coenzymes during FA synthesis.

Answer 11

ATP / Biotin

Question 12

Regulation of Acetyl-CoA Carboxylase:

Answer 12

Activators: Citrate / Insulin
*signals FED state and a need for glucose storage

Inhibitors: Glucagon / Epinephrine / high [AMP] / Palmitate / PUFA
*signals HUNGRY or EXERCISE and need for glucose release

*high carb/low fat diet can up-regulate gene expression for it as well

Question 13

Malonyl-CoA inhibits ___ which is the rate limiting step of FA degradation

Answer 13

Carnitine Acyltransferase

Question 14

Malonyl-CoA undergoes 7 reactions in the ___ to form Palmitate.

Answer 14

Fatty Acid Synthase Complex (aka. FAS Complex)

Question 15

FAS Complex is made of ____ each 7 enzyme activities and an acyl carrier protein.

Answer 15

2 identical dimers

Question 16

The ACP of the FAS Complex has a ___ that assists in moving the substrate along the different enzymatic active sites.

Answer 16

Flexible arm

Question 17

What pathway generates NADPH?

Answer 17

Pentose Phosphate Pathway (PPP)

Question 18

Incoming Malonyl-CoA binds to the ___ on the FAS Complex.

Answer 18

Cysteine (-SH) on the PAN acid

*Acetyl-CoA binds to the cysteine on the CYS end for the 1st step

Question 19

What are the 4 reactions in the FA synthesis catalyzes by the FAS Complex?

Answer 19

1. Condensation - forms a beta-ketoacyl group
2. Reduction
3. Dehydration
4. Reduction - forms a 4C fatty acyl group

Question 20

Insulin always activates a ___ which ___ a substrate.

Answer 20

Phosphatase / de-phosphorylates

*Glucagon and Epinephrine activate kinases (ex: PKA) that phosphorylate substrates

Question 21

Regulation of FAS Complex:

Answer 21

Activators: insulin / glucogcorticoid hormones (stress) / high carb, low fat diet

Inhibitors: high fat diet / starvation / PUFA

Question 22

FA chains longer than Palmitate are synthesized in the ___ or the ___.

Answer 22

SER (smooth ER) / mitochondria

• SER uses Malonyl- CoA as carbon donor
• mitochondria uses Acetyl-CoA as carbon donor

Question 23

Human beings cannot synthesize FA with a double bond beyond ___.

Answer 23

Carbon 9 and 10

*reason why people must consume essential fatty acids

Question 24

___ stores the most energy in the body.

A. Glycogen
B. TAGs
C. Proteins

Answer 24

B. TAGs in fat and muscle provide the most energy

Question 25

Where are TAGs made?

Answer 25

Intestinal cells => dietary intake

Hepatocytes and adipocytes => de novo synthesis

Question 26

Fatty acids must be activated by adding ___ before they can combine with other substrates (like glycerol)

Answer 26

CoA

*this is done by Fatty Acyl CoA Synthetase

Question 27

Deitary TAGs are broken down into ___ and ___ in the intestinal lumen by lipases.

Answer 27

MAG / FFA

Question 28

TAG synthesis in intestinal cells forms __ which are released into the lymphatic system before entering the blood.

Answer 28

Chylomicrons

*TAG synthesis in the liver forms VLDL

Question 29

The only organ that can directly convert glycerol into glycerol 3P is ____.

Answer 29

The liver.

Question 30

Sources of glycerol in FA synthesis:

Answer 30

Dietary (intestines)

Glucose / Glycerol (liver)

Question 31

TAG synthesis in hepatocytes (liver) is promoted by ___.

Answer 31

Excess carbohydrates

*reason why consuming carbs can lead to increase in fat

Question 32

TAG are stored in ___.

Answer 32

Adipocytes

Question 33

Long chain FA are complexed to ___ to inhibit sticking to the blood vessel.

Answer 33

Albumin

Question 34

What are the three major lipases involved in breakdown of TAGs?

Answer 34

HSL - hormone sensitive lipase

LPL - lipoprotein lipase

MAG - monoacylglycerol lipase

*ATGL (adipose triglyceride lipase) was recently found to also release DAGs from TAGs in HSL knockout mice

Question 35

How does Glucagon affect Perilipin in FA release from TAG?

Answer 35

Glucagon promotes phosphorylation of Perilipin

—> Perilipin will release and allow access to TAG in fat droplets

Question 36

____ prevents access of the lipases to the TAGs within fat droplets

Answer 36

Perilipin

Question 37

Fatty acids convert to form ___ to be able to pass through into the mitochondrial matrix.

Answer 37

Fatty Acyl Carnitine

Question 38

What is the rate limiting enzyme for Fatty Acid breakdown?

Answer 38

CPT1 (Carnitine Palmitoyltransferase 1)

*this is inhibited by Malonyl CoA, a substrate made in the RLS of FA synthesis

Question 39

What are the 4 steps of Beta Oxidation in FA degradation?

Answer 39

1. Oxidation
2. Hydration
3. Oxidation
4. Thiolysis

Question 40

___ is the most common ACAD that inherits defects.

Answer 40

MCAD (Medium Chain Acyl-CoA Dehydrogenase)

Question 41

When there is an odd number of C, such that Propionyl CoA forms during FA degradation ___ will add a carbon to continue degradation.

Answer 41

Propionyl CoA Carboxylase

*Requires Biotin

Question 42

VLCFA (very long chain fatty acids) are broken down in ___ while normal FA are broken down in the mitochondria.

Answer 42

Peroxisomes

*1st step is done by FAD-containing Acyl-CoA oxidase which generate hydrogen peroxide!

Question 43

Disorders in FA-oxidation lead to…

Answer 43

Inability of cells to break down FA for the use of energy

*therefore, main source of energy will be carbohydrate metabolism

Question 44

Carnitine is an analog of ___. It is not synthesized in the body, though ___ are rich in it.

Answer 44

Lysine / skeletal muscles

Question 45

Ketone bodies are made from ___.

Answer 45

Acetyl CoA

Question 46

What are the 3 most common ketone bodies?

Answer 46

Acetoacetate
Beta-hydroxybutyrate
Acetone

Question 47

Ketone bodies are produced only in the ___.

Answer 47

LIVER (within the mitochondrial matrix of hepatocytes)

Question 48

Diabetic Ketosis… explain

Answer 48

Diabetes = impairment in the uptake/storage of glucose

—> fatty acid release increases since glucose cannot be used for energy

—>high [fatty acids] = increased formation of Acetyl CoA

—> high [Acetyl CoA] = increased formation of Ketone Bodies

—> Ketone Bodies (are acidic) cause blood pH to drop

—> results in coma/death