Biochem - E3

Question 1

2 Classes of lipids

Answer 1

1. Fatty acid based
   - Amphipathic, micelle forming, soaps
   - Energy storage (fat deposits cushion organs & insulate against heat loss)
   - Membranes (electrical insulation of nerves), including phospholipids & sphingolipids
   - Signals.
2. Isoprenoids
   - Bile Acids/Salts
   - Membranes,
   - Signals,
   - Cofactors,
   - Fat soluble vitamins.

Question 2

At neutral pH, fatty acids are ____ and act as _____

Answer 2

Charged, soaps.

Question 3

Features of short chain FAs (<6)

Answer 3

• Produced in colon by microbiome
• Can cross blood brain barrier
• 6-10% of total energy (80% in coloncytes)

Question 4

Medium chain FAs (6-12) can be used as tx for…

Answer 4

Waldmann disease, epilepsy, chronic pancreatitis

Question 5

Long chain FAs (>12)

Answer 5

Are absorbed in the small intestine

Question 6

Excess carbohydrate is converted into _____ (default) or _______ (regulated) by the liver.

Answer 6

Excess carbohydrate is converted into FAs (default) or cholesterol (regulated) by the liver.

Question 7

FAs and cholesterol are packaged into VLDL (___________) by ________& ________.

Answer 7

FAs & CHL are packaged into Very Low Density Lipoprotein (VLDL) via TAG synthase and acyl cholesterol acyl transferase (ACAT).

Question 8

What is the characteristic apoprotein of VLDL?

Answer 8

Apoprotein of VLDL is Apo-B100 (formed from the same gene as B48).

Question 9

After release, the ApoCII of VLDL stimulates _____________ to hydrolyze FAs for storage in ______.

Answer 9

After release, the ApoCII of VLDL stimulates lipoprotein lipase (LPL) to hydrolyze FAs for storage in adipose.

(The LPL enzyme projects into the lumen of capillaries in many tissues - mostly adipose tissue, muscle, and some breast tissue)

• LPL is the same enzyme that works on chylomicrons

Question 10

What generates Intermediate Density Lipoprotein (IDL)?

Answer 10

When TAGs = Cholesterol esters (CEs), ApoC-II falls off of VLDL and forms IDL.

Question 11

All cells need cholesterol to modulate ___________________.

_______ is the major serum transporter for cholesterol.

Answer 11

All cells need cholesterol to modulate membrane fluidity.

LDL is the major serum transporter for cholesterol.

Question 12

How is LDL generated?

Answer 12

The liver expresses Hepatic Triglycerol Lipase (HTGL) to remove remaining TAGs from IDL to make LDL, the major transporter of cholesterol to tissues.

Question 13

Does VLDL or LDL have longer half-life?

Answer 13

VLDL has a half-life of about 3 hours while LDL has a half-life of days.

Question 14

What is the danger of LDL circulating for too long?

Answer 14

If LDL circulates too long, it gets oxidized, stimulates monocyte recruitment into the blood vessel wall.

Monocytes differentiate to macrophages and take up ox-LDL (via scavenger receptors).

If they take up too much –> become foam cells and die.

Dead foam cells (fatty streak), + smooth muscle cell growth (via signals from foam cells) + matrix degradation forms an atherosclerotic plaque.

Question 15

A function of HDL is the promotion of cholesterol efflux from cells… why is this so useful?

Answer 15

Efflux of cholesterol from foam cells –> reduction in foam cell formation; macrophages may accumulate, but are not converted into foam cells.

Inflammatory process is arrested to a certain extent.

So, HDL is anti-inflammatory and also protects against the development of atherosclerosis.

Question 16

HDL is released as an “empty shell” by the liver intestine. It is released with ____________ & __________, ____________ (its characteristic apoproteins). CE’s get picked up later.

Answer 16

HDL is released with phospholipids & ApoA-I, ApoA-II (its characteristic apoproteins). CE’s get picked up later.

Question 17

Where does liver get cholesterol: synthesis, ________ ___________, mature HDL, LDL, ____________ (aka IDL).
As known as the “_____________________” pathway

Answer 17

Where does liver get cholesterol: synthesis, chylomicron remnants, mature HDL, LDL, VLDL remnants (aka IDL).
As known as the “reverse cholesterol transport” pathway

Question 18

What is the role of Lecithin Cholesterol Acyl Transferase (LCAT) as HDL travels through the blood and encounters cells with excess cholesterol on their surfaces?

Answer 18

Lecithin Cholesterol Acyl Transferase (LCAT) is stimulated by ApoA-1 and transfers CHL from cell to HDL.

LCAT removes a fatty acid from a membrane phospholipid to form CEs out of the excess cholesterol that has been moved to the cell surface. The lysolecithin that is produced can be repaired .

Question 19

What is the fate of HDL full of CEs?

Answer 19

They can be bound by Scavenger Receptor-BI (SRB1 or HDL receptor) on liver & adrenals for endocytosis & degradation.

Question 20

What does a 30% increase in LDL lead to?

What about a low LDL:HDL (1.5:1 rather than 3:1)?

Answer 20

30% increase in LDL = 3x risk of coronary mortality

A low LDL:HDL (1.5:1 rather than 3:1) halves risk of CHD.

Cholesterol is the same in LDL and in HDL: just packaged differently

Question 21

Describe the composition of chylomicrons.

Answer 21

Lipids (mostly TAG)&raquo_space; protein: low density

Question 22

Describe the composition of HDL

Answer 22

Lipids (mostly CEs) &laquo_space;protein: high density

Question 23

Arrange the post absorptive lipoproteins in order of TAG content from MOST to LEAST.

Answer 23

Most TAG –> Least TAG

Chylomicron, VLDL, IDL, LDL

Question 24

Describe Familial Hypercholesterolemia

Answer 24

Defective receptor for receiving LDL (LDL-R defect leads to greatly elevated LDL).

Question 25

Excess dietary carbohydrate become _______ and ________, packaged into VLDL

Answer 25

Excess dietary carbohydrate becomes Fatty Acids and cholesterol, packaged into VLDL

Question 26

Apo-C-II stimulate ___________________ to hydrolyze TAG from VLDL. VLDL loses ApoC-II, generating ___

Answer 26

Apo-C-II stimulates lipoprotein lipase (LPL) to hydrolyze TAG from VLDL

VLDL loses ApoC-II, generating IDL

Question 27

_______________________ removes TAGs of IDL to make LDL

Answer 27

Hepatic Triglycerol Lipase (HTGL) removes TAGs of IDL to make LDL

Question 28

____ is released with phospholipids & ApoA-I, ApoA-II and Apo’s C & E

Apo’s _____ are passed to VLDL & chylomicrons
_____ Activates LCAT to form CEs out of excess cholesterol

Answer 28

HDL is released with phospholipids & ApoA-I, ApoA-II and Apo’s C & E

Apo’s C (& E) are passed to VLDL & chylomicrons
ApoA-I Activates LCAT to form CEs out of excess cholesterol

Question 29

Mature HDL is bound by ________________

Answer 29

SR-BI receptors

Question 30

FAs are released from adipose cells when _________ activates ___________________- to phosphorylate and activate Hormone Sensitive _______ in adipose cells.

Answer 30

FAs are released from adipose cells when glucagon activates cAMP-dependent protein kinase to phosphorylate and activate Hormone Sensitive Lipase in adipose cells.

Question 31

FAs are carried by _________________, and activated inside cells that want to use them for energy by _______________.

(as for TAG formation in intestine) of Beta oxidation

Answer 31

FAs are carried by serum albumin, and activated inside cells that want to use them for energy by acyl-CoA synthetase.

Question 32

Long chain FAs are transferred to carnitine by ____________________ (CPT I, aka CAT I), and transferred into the ______________ by _____________________ (in exchange for carnitine coming out).

CPT II remakes acyl-CoA in the ______.
CPT I is inhibited by ______________, the first product in fatty acid synthesis.

Answer 32

Long chain FAs are transferred to carnitine by Carnitine Palmitoyl Transferase I (CPT I, aka CAT I), and transferred into the mitochondrial matrix by Carnitine:Acylcarnitine Translocase (in exchange for carnitine coming out).

CPT II remakes acyl-CoA in the matrix. CPT I is inhibited by malonyl-CoA, the first product in fatty acid synthesis.

Question 33

FA oxidation proceeds via a _________ specific for the length of the FA.

2-3 Enoyl CoA Hydratase, 3-OH-acylCoA-dehydrogenase, & 3-keto acylCoA thiolase will catalyze ____________________ & produce ______ and ______ & _______.

Answer 33

FA oxidation proceeds via a dehydrogenase specific for the length of the FA.

2-3 Enoyl CoA Hydratase, 3-OH-acylCoA-dehydrogenase, & 3-keto acylCoA thiolase will catalyze shortening of the fatty acid by 2 carbons & produce acetyl-CoA and FADH2 & NADH.

Question 34

Every time FA is shortened by 2C –> gen ________ (can make ___ ATP) and some NADH/FADH to make more ATP.

Answer 34

Every time FA is shortened by 2C –> gen acetyl-CoA (can make 12 ATP) and some NADH/FADH to make more ATP.

Question 35

The energy yield for FA oxidation is ______ per gram than that of glucose

Answer 35

The energy yield for FA oxidation is higher per gram than that of glucose.

Question 36

The cis 2-3 trans double bond situation (in beta oxidation) is resolved by a couple enzymes…

Answer 36

2,4 dienoyl-CoA reductase reducing one double bond & enoyl CoA isomerase.

Question 37

Oxidation of the alpha (alpha oxidation) carbon occurs in the ________ and is used to deal with the ______________ on _________ originally derived from plants.

Alpha carbon oxidation of phytanic acids is followed by beta oxidation to yield ________.

Answer 37

Alpha oxidation occurs in the peroxisomes and is used to deal with the methyl branch on phytanic acids originally derived from plants.

Alpha carbon oxidation of phytanic acids is followed by beta oxidation to yield propionyl CoA.

Question 38

Genetic deficiency in alpha-oxidation can lead to…

Answer 38

Neurological disorder (Refsum’s disease)

Question 39

FA disorders (FAOs)

Answer 39

Autosomal recessive metabolic disorders, enzymes necessary for fatty acid breakdown are unavailable or have reduced activity

Exp. hepatic failure, encephalopathy, heart and eye complications. General problems with muscle development.