Biochemistry: Storage Of Energy- Fats

Front 1

Where does pancreatic lipase work? What does it do?

Back 1

Breaks down triglycerides in the intestinal lumen (brush border)

Front 2

Where does hormone-sensitive lipase work? What does it do?

Back 2

Key enzyme in fat degradation found in adipose tissue.

Unlike liver and intestine, adipose tissue releases lipid as free fatty acids instead of lipoproteins.

Front 3

Where does hepatic lipase work?

Back 3

Anchored to surface of hepatocytes in liver.

Front 4

Where does lipoprotein lipase (LPL) work?

Back 4

On the surface of endothelial cells in the capillary.

Front 5

How are triglycerides absorbed?

Back 5

Dietary fat triglycerides are broken down by pancreatic lipase with the help of bile salts into 2-monoacyl glycerol + FFA and are then absorbed at the brush border of mucosa cells.

Front 6

How are triglycerides transported after absorption?

Back 6

To re-synthesize TGs, CoA is added onto FFA by Acyl-coA synthetase that uses ATP-->AMP. Two of these then combines with the 2-monoacyl glycerol to reform the TG. Long chained TG are packaged into chylomicrons and transported from lymph --> blood --> Liver.
Short and medium FFA are transported directly through the portal to the liver via albumin. (No resynthesis of short and medium chain TG)

Front 7

Which two forms of fatty acids are absorbed from the gut? Are they completely digested to glycerol and free fatty acids before absorption?

Back 7

Free fatty acids + 2-monoacyl glycerol

No, the 2-monoacyl glycerol is glycerol with one fatty acid attached to the middle carbon.

Front 8

What enzyme is involved in fatty acid activation? Why is this necessary?

Back 8

Acyl-CoA synthetase, it activates the FFA so that it can attach onto the 2-monoacyl glycerol, reforming the TG so that it can be transported.

Front 9

Is phosphatidic acid involved in triglyceride synthesis in intestinal mucosa cells?

Back 9

No, it is involved in triglyceride synthesis in the liver.

Front 10

What is the source of glycerol for triglyceride esterfication in the mucosa?

Back 10

2-monoacylglycerol

Front 11

How are free fatty acids transported into the mucosal cells?

Back 11

Through the brush border, packaged into micelles.

Front 12

Are the triglycerides that are assembled in the mucosa picked up by the hepatic portal like all the other products of digestion? What happens to get them into the general circulation?

Back 12

No, they are packaged into chylomicrons that then enter the lymph circulation through the thoracic duct into the left brachiocephalic vein and finally to the liver.

Front 13

What's the difference between medium and short chain transport in the blood and long chain transport? Why do they have to be different?

Back 13

Medium and short chain FFA can go through the mucosa cell and get transported through the portal vein directly to the liver by attaching to albumin.

Long chain FFA have to be resynthesized into TG, packed into chylomicrons, go through the lymph, vein, and finally to the liver. They circulate to tissues. Also, long chain FA needs carnitine to get into the mitochondria.

Front 14

Trace triacylglycerol from a slice of pizza to an adipose cell on your waistline.

Back 14

Once it gets into the gut, pancreatic lipase with the help of bile salts digest it into 2 FFAs and 2-monoacylglycerol. Those get absorbed into the mucosal cell where the FFA gets reactivated, and put back on the 2-monoacylglycerol into triglycerides and packaged into chylomicrons in the ER. Then, they go through the lymph and into the vein. Finally, they reach the capillaries where LPL of the endothelial cells digest it back into FFA and 2-monoacylglycerol so they can be absorbed into adipose cells. Short and medium travel directly to the liver, where they are packaged and sent out.

Front 15

What's the origin of glycerol used for fat (triglyceride) storage?

Back 15

DHAP from glycolysis ---> glycerol 3-PO4 (by glycerol3PO4 DH)

Front 16

What is the role of insulin in stimulating the synthesis and storage of fat from glucose? (5 things)

Back 16

Stimulates glucose uptake in cell, which = more DHAP. DHAP ---> glycerol3PO4 uses glycerol3PO4 DH, which is also stimulated by insulin.

Stimulates LPL (TG--> 2MAG + 2x FFA).

Stimulates glycerol phosphate-acyl transferase (enzyme that adds the first FA to glycerolphosphate in biosynthetic pathway)

Stimulates acetyl-CoA carboxylase.

Front 17

What is the role of insulin in suppressing mobilization of fat from TG?

Back 17

Insulin inhibits hormone-sensitive lipase, which is a key enzyme in fat degradation (is active in it's phosphorylated form, but insulin inhibits cAMP activity from phosphorylating it)

Front 18

What vitamins are involved in the synthesis of a triglyceride from glucose?

Back 18

Biotin is a vitamin that is associated with all carboxylase enzymes; Riboflavin in FAD; Niacin in NADH; Vitamin B found in CoA

Front 19

What key glucose to fat enzymes are stimulated by insulin?

Back 19

Insulin stimulates: Phosphofructokinase (important in glycolysis and formation of fructocse-1,6-biphosphate)

PDH Phosphatase (dephosphorylates Pyruvate DH making it active, increasing activity and formation of acetyl-CoA)

Glycerol-phosphate-acyl transferase: Adds on the first acyl group onto glycerol.

Front 20

What key fat mobilizing enzyme is inhibited by insulin? (hint: this is the same enzyme that is stimulated by a cup of coffee before a race)

Back 20

Hormone-sensitive lipase

Front 21

How does the body metabolize free glycerol?

Back 21

It is transported directly to the liver for gluconeogenesis.

Front 22

Where is glycerol kinase found?

Back 22

Liver

Front 23

What steps are needed to bring glycerol carbons into the glycolytic pathway?

Back 23

Glycerol-3PO4 is converted to DHAP by glycerol-3-phosphate DH.

Front 24

What steps are needed to bring glycerol into the gluconeogenenis pathway?

Back 24

Glycerol needs to be phosphorylated by glycerol kinase

Front 25

What's the process for converting acetylCoA into MalonylCoA? What's so special about this step?

Back 25

AcetylCoA ---->MalonylCoA
Enzyme: acetylCoA carboxylase
CO2 needs biotin
ATP consumed
*this is the committed step and the rate limiting step for fatty acid synthesis.

Front 26

What is the allosteric regulation for acetylCoA carboxylase?

Back 26

Stimulated by citrate

Inhibited by palmitoylCoA (CoAthioesters of long chain FA) and AMP

Front 27

What is the hormonal regulation of acetylCoA carboxylase?

Back 27

Glucagon- phosphorylation through cAMP, which inactivates acetylCoA barboxylase. This stops fatty acid synthesis

Insulin- induces a phosphodiesterase that degrades cAMP, dephosphorylates acetylCoA carboxylase, which activates the enzyme and increases FA synthesis.

Front 28

What is the initiation step of fatty acid synthesis?

Back 28

Binding of acetyl and malonyl to the fatty acid synthase complex.

Acetyl attaches to the ketoacyl-synthase (cys-SH) end

Malonyl attaches to the ACP (pan-SH) end

Front 29

What is the elongation cycle of fatty acid synthesis?

Back 29

The acetyl group is moved onto the malonyl group (cleaving off the COO-). Then, three reactions use NADPH to reduce the C=O to -CH2, and finally, the entire thing is moved back up to the ketoacyl synthase (cys-SH) end. A new malonyl is then attached to the ACP (pan-SH) end and the entire process is repeated, this time moving the newly synthesized acyl (instead of acetyl) group down.

*Note: add 2 carbons at a time because malonyl's COO- is cleaved off)

Front 30

What is the cofactor that reduces the 2-ketoacyl group on the elongation chain that is attached to ACP?

Back 30

NADPH (from PPP)

Front 31

What is the termination step for fatty acid synthesis?

Back 31

Once 16 carbon (palmitate-ACP) is produced, thioesterase cleaves at the ACP.

Front 32

How does acetylCoA get into the cytoplasm?

Back 32

acetylCoA attaches to OAA via citrate synthase and then goes through the citrate shuttle where it is then broken down back into acetylCoA and OAA by ATP-citrate lyase (ATP-ADP)

Front 33

How does OAA get back into the mitochondria (two methods)?

Back 33

OAA gets converted to malate by malate dehydrogenase and NADH-->NAD+ (uses energy). Malate is then shuttle back and converted back to OAA using the same enzyme, but NAD -->NADH (creates energy).

Or, still in the cytosol, malate can be converted into pyruvate using malic enzyme (NADP-->NADPH, loses a CO2) and then pyruvate can get into the mitochondria, which is then converted back into OAA using pyruvate carboxylase using ATP and CO2.

Front 34

How does the product of fatty acid synthase enzyme (palmitate) get further elongated?

Back 34

Microsomes on the ER can elongate beyond 16 carbons, also 2 carbons at a time.

Front 35

How does the body produce desaturated fatty acids?

Back 35

Desaturase enzymes (membrane bound on ER). They are monooxygenases that use molecular oxygen as the oxidant and either NAD or NADPH as the cofactor. The first double bond is inserted at delta9. Can't insert double bonds beyond delta9.

Front 36

What are essential fatty acids? What can they be precursors for?

Back 36

Linoleic acid (has a delta12 double bond)
Linolenic acid (has a delta12 and delta15 double bond)

Linolenic acid is a precursor for arachidonate (20:4: Delta 5,8,11,14)

Front 37

What's the cellular compartmentation of fatty acid metabolism in the liver?

Back 37

Acetyl-CoA formation occurs inside the mitochondrial matrix, and is then transported out into the cytoplasm for fatty acid synthesis