Lecture 41

Question 1

What are 11 consequences of obesity?

Answer 1

1) Type 2 Diabetes - can lead to heart disease, kidney failure, blindness, amputation of the feet or legs, & nerve damage
2) Heart Disease - hardening of the arteries, heart attack, & angina
3) High Blood Pressure - can lead to heart disease, stroke, kidney failure, & vision loss
4) High cholesterol - can lead to heart disease, stroke, & kidney failure
5) Obstructive sleep apnea - associated with high blood pressure
6) Acid reflux/GERD - can lead to esophagitis, Barrett’s esophagus, & esophageal cancer (adenocarcinoma)
7) Cancer
8) Depression
9) Osteoarthritis & Joint Pain - can lead to loss of mobility
10) Stress urinary incontinence
11) Female reproductive health disorder - can lead to infertility & sexual dysfunction

Question 2

After a five year follow up of obese patients who have been treated, which treatment options are most effective (in order)?

Answer 2

1) Bariatric Surgery (gastric bypass, gastric banding) - 50-70%
2) Diet & Exercise - 2-5%
3) Prescription weight loss medications - 0%

Question 3

How are dietary lipids broken down?

Answer 3

1) Dietary lipids are broken down by Pancreatic Lipase (alpha lipase) and transported through the lymph system
2) Triacylglycerides are broken down in the lumen by lipases to form (diacylglycerides –> monoacylglycerol) fatty acids + monoacylglycerols
3) Fatty acids + monoacylglycerols are transported into mucosal cells to reform triacylglycerides
4) Triacylglycerides along with other lipids and proteins are taken by chylomicrons to the lymph system

Question 4

How are fatty acids named?

Answer 4

1) Start from the carboxyl group on one end (1) and number each carbon to the other end of the chain in increasing number order (2, 3, 4, 5, etc.)
2) Assign alpha to the first carbon next to the terminal carboxyl group and continue through the greek alphabet until reaching the end of the fatty acid chain
3) Omega is always the last carbon in the fatty acid chain. Omega 3 fatty acids are named so because the double bond in the fatty acid chain is the 3rd carbon in the chain including the omega carbon

Question 5

How are dietary lipids transported after breakdown?

Answer 5

1) Triacylglycerides along with other lipids and proteins are taken by chylomicrons to the lymph system
2) Upon reaching a destination tissue, chylomicrons are hydrolyzed by lipoprotein lipase (LPL) on the triglyceride portion, forming fatty acids in the destination tissue
3) Fatty acids can be oxidized for energy. However, if energy is not needed fatty acids will be stored in adipose tissue

Question 6

Why do you have to fast before certain medical procedures?

Answer 6

Chylomicrons can make the blood appear milky, interfering with observation of other components of the blood

Question 7

What is the function of Orlistat?

Answer 7

Orlistat inhibits pancreatic lipase in order to prevent the absorption of lipids

Question 8

What is the function of Lovaza and associated omega-3 fatty acids?

Answer 8

1) They inhibit the synthesis of triacylglycerol in the liver
2) Specifically, they inhibit acyl CoA: 1,2 diacyl glycerol acyl transferase (incorporation of fatty acids into triacylglycerols)
3) They may also stimulate the activity of LPL

Question 9

What is Olestra?

Answer 9

A large dietary lipid that is too large to be hydrolyzed by pancreatic lipase

Question 10

Where do all carbons from glucose end up?

Answer 10

They end up in mitochondria

Question 11

Where does fatty acid synthesis occur?

Answer 11

Fatty acid synthesis occurs in the cytosol

Question 12

How are carbons that are shuttled to the mitochondria from glycolysis and for the krebs cycle used in fatty acid synthesis back in the cytosol?

Answer 12

1) Pyruvate is broken down into Acetyl CoA or Oxaloacetate
2) Oxaloacetate and Acetyl CoA combine to form citrate
3) Citrate is transported across a Citrate translocase in the inner mitochondrial membrane from the mitochondrial side to the cytosol
4) Citrate is broken down into Oxaloacetate and acetyl CoA
5) Acetyl CoA is used in fatty acid synthesis

Question 13

What three components form fatty acids?

Answer 13

1) Acetyl CoA (from glucose)
2) Malonyl CoA
3) NADPH (hexose monophosphate shunt/pentose phosphate pathway)

Question 14

How is Malonyl CoA formed?

Answer 14

Catalyzed by Acetyl CoA Carboxylase (ACC), a multienzyme containing two enzyme activities and BCCP (biotin carboxyl carrier protein)
ACC is the rate-limiting enzyme of FA Synthesis
1. BCCP-biotin carboxyl carrier protein- 10,000 mol. wt; no enzymatic function.
2. Biotin Carboxylase (BC)
BCCP + HCO3- + ATP –> BCCP-CO2 + ADP + P
3. Transcarboxylase (TC)
BCCP-CO2 + Acetyl CoA –> Malonyl CoA + BCCP

Question 15

What are the reactions for overall fatty acid synthesis?

Answer 15

1) Acetyl CoA + HCO3- + ATP –> Malonyl CoA + ADP +P
Acetyl CoA Carboxylase
2) CH3-CO-SCoA +7 CO2-CH2-CO-SCoA + 14 NADPH + 14 H+
Fatty Acid Synthase complex: 6 enzyme activities and
ACP (acyl carrier protein) (size ~10,000 daltons)
3) Palmitic Acid + 14 NADP+ + 8 CoA + 7 CO2 + 7 H2O (C:16 Fatty acid)

Question 16

What is the acyl carrier protein (ACP) prosthetic group very similar to in structure?

Answer 16

CoA

Question 17

How do the functions of ACP and CoA differ?

Answer 17

1) ACP is used for fatty acid synthesis

2) CoA is used for fatty acid metabolism/degradation

Question 18

What is the difference between Acyl carrier protein (ACP) types 1 and 2?

Answer 18

Type I FAS-a multi-enzyme complex in eukaryotes

Type II-FAS-Separate individual enzymes in prokaryotes

Question 19

Describe the formation of hexa decanoic acid

Answer 19

1) Acetyl-SACP + Malonyl-SACP combine to form Acetoacetyl-SACP
2) Acetoacetyl-SACP forms Beta-hydroxybutyryl-SACP
3) Beta-hydroxybutyryl-SACP forms Crotonyl-SACP or Enoyl-SACP
4) Crotonyl-SACP or Enoyl-SACP forms Butyryl -SACP
5) Butyryl -SACP + Malonyl-SACP forms Hexanoyl –SACP (C6)
6) Hexanoyl-SACP + Malonyl-SACP forms Octanoyl-SACP (C8)
7) Continue this addition of 2 carbon chains until you reach the formation of Hexadecanoyl-SACP, which is converted to Hexadecanoic acid (C16 FA)

Question 20

How is fatty acid synthesis regulated?

Answer 20

1) High levels of Citrate promotes fatty acid synthesis (high activity ACC polymer)
2) High levels of Palmitoyl CoA & Malonyl CoA downplays fatty acid synthesis (low activity ACC dimer)

Question 21

Describe ACC activation and inactivation

Answer 21

1) When ACC is inactive, it is in the phosphorylated state
2) ACC can be dephosphorylated by protein phosphatase 2 (stimulated by insulin) to form a partially active form of ACC (partially activated dimer)
3) This dimer can then cause the formation of citrate, which enhances the activation of ACC to a highly active polymer
4) If the polymer is phosphorylated, it will become only a partially active ACC polymer
5) Removal of citrate from this form of ACC will reform the inactive form of ACC
6) Glucagon stimulates the phosphorylation of the partially activated ACC dimer activating the AMP Activated Protein Kinase (NOT cAMP Activated Protein Kinase) and forming the inactive form of ACC

Question 22

In eukaryotic fatty acids, where can double bonds be formed?

Answer 22

1) At or before the 9 or 10 carbon (delta 9/omega-9)

2) Mammals cannot introduce double bonds beyond C9

Question 23

To what end of a fatty acid chain are carbons always added?

Answer 23

To the carboxyl end

Question 24

How can a double bond be formed beyond C9?

Answer 24

Elongate the fatty acid chain after producing a double bond before the C9. This will cause the carbons to be renumbered from the carboxyl end