M&n Week 2: Lipid Metabolism In Absorptive State

Front 1

The absorptive state generally occurs within how many hours following a meal?

Back 1

2-4 hours

Front 2

What is the dominant hormone that regulates the absorptive state?

Back 2

Insulin

Front 3

Insulin is secreted in response to what?

Back 3

1. High glucose
2. High amino acid
(in portal circulation)

Front 4

What are the metabolic functions of the liver in the absorptive state?

Back 4

1. Glycolysis
2. Glycogen synthesis
3. De novo fatty acid synthesis

Front 5

What type of transporter allows glucose to enter the liver?

What is the relative Km/affinity of this transporter for glucose?

Back 5

GLUT2 (insulin independent)

*High Km (low affinity)-- will NOT be limiting.

Front 6

When Glucose-6-PO4 levels are high in the liver, the compound is diverted from glycolysis into which metabolic pathway?

What important compound is produced in this pathway?

Back 6

Hexose-mannose pathway

*NADPH produced (used for all reductive biosynthetic pathways)

Front 7

In the presence of high levels of ATP, which synthetic pathway will acetyl-CoA enter?

Back 7

Fatty acid synthesis

Front 8

Fatty acids formed via de novo synthesis in the liver will be used to form what compounds?

How are the fatty acids released from the liver?

Back 8

Fatty acids are used to make triacylglycerol

TAG is packaged into VLDL particles are released from liver

Front 9

During the fed state, what compounds does adipose tissue absorb?

Back 9

1. Fat (via chylomicrons)
2. Glucose (from the blood)

Front 10

What is the most important task for adipose tissue after a meal?

Back 10

Lipid storage

Front 11

Describe the effect of insulin on:
1. Lipoprotein lipase
2. Fatty acid transport proteins
3. Hormone sensitive lipase

Back 11

1. INCREASES Lipoprotein lipase
2. INCREASES Fatty acid transport proteins
3. DECREASES hormone sensitive lipase

Front 12

What type of transporter allows the entry of glucose into adipose cells?

Back 12

GLUT4 (insulin-dependent)

Front 13

What is the most important fuel for resting muscle in the fed state?

Back 13

Glucose
(Used for glycolysis and glycogen synthesis)

Front 14

During the absorptive state, what does the brain rely on for energy metabolism?

Back 14

Glucose

Front 15

Which tissues are responsible for lipogenesis?

Back 15

1. Liver
2. Adipose tissue

Front 16

What is the effect of insulin on lipogenesis?

Back 16

Promotes lipogenesis
(does this through phosphorylation cascades and increasing the rates of synthesis of transcription factors that regulate lipogenic enzymes)

Front 17

Which organ is the primary source for de novo fatty acid synthesis?

Back 17

Liver

Front 18

De novo fatty acid synthesis is driven by the availability of which substrates?

Back 18

1. Acetyl-CoA
2. NADPH

Front 19

Which metabolic pathway provides the primary source of glycerol phosphate backbones for TAG synthesis?

Back 19

Glycolysis

Front 20

Where does cytosolic acetyl-CoA come from?

Back 20

Inner mitochondrial matrix (result of glycolysis)

Front 21

Since CoA cannot penetrate the inner mitochondrial membrane, how is acetyl-CoA transported from the mitochondrial matrix into the cytosol?

Back 21

Acetyl-CoA is converted to citrate, which can be transported across the inner mitochondrial membrane. Once citrate reaches the cytosol, CoA can be added to it to reform Acetyl-CoA

Acetyl-CoA + OAA ---citrate synthase ---> Citrate + CoA

Front 22

Which enzyme converts acetyl-CoA and oxaloacetate to citrate?

Where does this reaction take place?

Back 22

Citrate synthase

*Mitochondrial matrix

Front 23

Which enzyme converts citrate and CoA into Acetyl-CoA and Oxaloacetate?

Where does this reaction take place?

Back 23

ATP-citrate lyase

*Cytosol

Front 24

Generation of NADPH in the cytosol occurs through which 2 processes?

Which process is the major supplier?

Back 24

1. Hexose Monophosphate Pathway <----MAJOR supplier
2. Malic enzyme

Front 25

For every Glucose-6-PO4 that enters the hexose-monophosphate pathway, how many NADPHs are produced?

Back 25

Two

Front 26

What is the function of malic enzyme?

Back 26

Acts on oxaloacetate that is produced as a result of citrate lyase in cytosol.
*Minor source of NADPH

OAA --> Malate (gets decarboxylated) --> pyruvate

Front 27

Which enzyme is responsible for the synthesis of malonyl-CoA?

Back 27

Acetyl-CoA carboxylase

Front 28

How is the assembly of acetyl-CoA carboxylase allosterically activated and inhibited?

Back 28

Activated by citrate
Inhibited by long-chain fatty acyl CoA

Front 29

What is the affect of citrate on acetyl-CoA carboxylase?

Back 29

Promotes formation of the complex (allosteric activation)

Front 30

What is the affect of long-chain fatty acids on acetyl-CoA carboxylase?

Back 30

Allosteric inhibition discourages assembly of the complex

Front 31

What is the affect of insulin on acetyl-CoA carboxylase?

Back 31

Activation
(insulin promotes protein phosphatase, which activates ACC by dephosphorylation)

Front 32

Is acetyl-CoA carboxylase active in its phosphorylated or dephosphorylated form?

Back 32

Dephosphorylated form

Front 33

Which enzyme activates acetyl-CoA carboxylase?

Back 33

Protein phosphatase
(dephosphorylates the complex)

Front 34

Which enzyme inhibits acetyl-CoA carboxylase?

Back 34

cAMP-dependent protein kinase
(phosphorylates the complex)

Front 35

What is the effect of glucagon and epinephrine on acetyl-CoA carboxylase?

Back 35

Inactivate it via cAMP protein kinase

Front 36

Which enzyme is responsible for the synthesis of palmitate?

Back 36

Fatty acid synthase (FAS) complex

Front 37

The synthesis of palmitate begins with which substrates?

Back 37

1. Acetyl-CoA (primer)
2. Malonyl-CoA

Front 38

How many times is the fatty acid synthesis cycle repeated to produce palmitate?

Back 38

7 times

Front 39

How many carbons compose palmitate?

Back 39

16 carbons

Front 40

T or F

Fatty acid synthase complex is a highly regulated enzyme.

Back 40

FALSE

Fatty acid synthase is not regulated; as long as substrates are available it performs fatty acid synthesis

Front 41

What are the two sources of glycerol phosphate?

Back 41

1. Partial flux through glycolysis (DHAP ---glycerol-P-dehydrogenase--> Glycerol-PO4)
2. Direct phosphorylation of glycerol by glycerol kinase (occurs in liver)

Front 42

What must happen to fatty acids before they can be esterified to glycerol-PO4?

Back 42

Must be activated to fatty acyl-CoA

Front 43

Which enzyme esterifies fatty acyl-CoA to glycerol-PO4?

Back 43

Acyltransferase

Front 44

Which two enzymes are involved in TAG synthesis from new fatty acids?

Back 44

1. Acyltransferase
2. Phosphatase

Front 45

Describe the sequence of TAG synthesis from new fatty acids.

Back 45

1. Glycerol-PO4
2. Lysophosphatidic acid (1st fatty acyl added)
3. Phosphatidic acid (2nt fatty acyl added)
4. Diacylglycerol (PO4 removed)
4. Triacylglycerol (3rd fatty acyl added)