Week 8 Flashcards

lipid metabolism

1
Q
Fatty acids (FA) 
(function, synthesis, stimulator)
A

used as fuel in the body
Synthesized from glucose
Stimulated by insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Triacylglycerol (TAG)

Function, synthesis, transport/location

A

is the storage form of FA made in the liver.
Major dietary lipid
Travel in circulation as chylomicrons (dietary) or VLDL (endogenously synthesized)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How are Dietary Lipids digested?

A

Emulsified in small intestine by bile salts and Pancreatic lipase and colipase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pancreatic lipase and colipase function

A

Hydrolyzes TAGs into free FAs and esterified glycerol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

pancreatic esterases function

A

remove fatty acids from other compounds (cholesterols, etc)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens to Lipid/Bile micelles

A

Lipid portion is absorbed into the intestinal epithelial cells
(Chylomicrons)
Bile is resorbed in the ileum, to be re-used.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Do short and medium FA chains need bile?

A

No, they are absorbed directly into cells & will enter blood, transported by serum albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Synthesis of Chylomicrons

A
  1. Free FAs and 2-MG are re-formed into TAG in the intestinal smooth endoplasmic reticulum
  2. TAGs must be transported in lipoprotein particles due to insolubility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

chylomicrons function

A

Transport of dietary fats

Newly released chylomicrons are called ‘nascent’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

ApoE

A

ligand for membrane receptors on many cells (esp liver), allows entry into cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

ApoCII

A

activator of lipoprotein lipase (LPL)

Capillary endothelial cells, muscle and adipose tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

chylomicron maturation

A

HDL in lymph and blood will transfer proteins to chylomicron, ‘maturing’ it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What tissues use oxidation of FA as a fuel source? And when?

A

primary fasting fuel source in cardiac, skeletal muscle, and liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What tissues use the conversion of FAs to ketone bodies?

A

major fasting fuel source for brain, gut, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Long Chain FAs are a predominant source of…

A

predominant source of oxidation for fuel during fasting states

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Transport of Long Chain FAs

what releases them, how it travels through the blood, how it gets to the liver, and final destination when in the cell

A

Released from adipocytes by lipases
Travel in hydrophobic pocket of albumen through the blood
Transported into cell either via passive diffusion through bilayer or facilitated with fatty acid binding protein
Inside the cell, the FA is transported to mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Activation of Long Chain FAs

A

Must be activated by acyl-CoA before they can be oxidized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acyl-Coa synthetase only activates…

A

long chain FAs, and is in ER, outer mitochondrial membrane, and peroxisome membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Very long chain synthase location

A

present in peroxisomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

medium chain synthetase location

A

present in mitochondrial matrix of liver and kidney cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Transport of Long Chain FA into MT

A

Carnatine serves as the transporter between outer and inner mitochondrial membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

β-Oxidation

A

Sequentially cleaves the fatty acyl group into 2C acetyl-CoA units, starting with the carboxyl end attached to the CoA.
β carbon must be oxidized first

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

β-Oxidation: step 1

A

double bond formed between β and α carbons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

β-Oxidation: step 2

A

water donates OH to β-carbon; and H to α-carbon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
β-Oxidation: step 3
hydroxyl group of β carbon oxidized to a ketone
26
β-Oxidation: step 4
bond between α and β carbons is cleaved by adding a coenzyme A (CoASH) to the βcarbon
27
Energy Yield of β-Oxidation
1 mole of palmityl-CoA converted to 8 mole of acetyl CoA yields: 28 mole ATP
28
Oxidation of Odd-Chain-Length FAs
Will undergo β oxidation rounds until there are 5 carbons left
29
Oxidation of Medium-Chain FAs
Activated to acyl-CoA derivatives, then oxidized to acetyl CoA via β-oxidation spiral
30
Medium-chain-length acyl-CoA synthetase has a broad range of...
specificity Can bind drugs which are approx. same size Salicylate (aspirin metabolism) and Valproate (anti epileptic)
31
where are very long chain FAs oxidized?
exclusively in peroxisomes
32
what tissues can not use FAs as fuel source?
RBCs (no mitochondria!) Adipocytes Brain
33
Ketone bodies function
serve as major source of energy in these tissues
34
where are ketone bodies synthesized? released? what is it converted into?
Synthesized in liver from acetyl CoA (generated in β-oxidation) Released into the blood as ketone bodies – re-converted to acetyl CoA in tissues for TCA cycle
35
Ketogenic diets
High protein, low carb diets are considered ‘ketogenic’ | High amounts of ketogenic amino acids
36
How is Ketogenesis regulated?
inhibited by insulin and feeding | activated by fasting and increases in cAMP and lipolysis
37
Skeletal muscle preferences for Fuel Sources
Skeletal muscle will preferentially use FAs over glucose as fuel as FA concentration increases in blood
38
FA Synthesis | what stimulates it, location, precursor, products
Stimulated when excess calories are ingested. Occurs primarily in the liver, process begins with glycolysis, citrate from glycolysis moves to cytosol and reforms acetyl CoA. Acetyl CoA is converted to malonyl CoA.
39
What is FA Synthase Complex? What does it create?
Large enzyme complex, many subunits. Creates 16 C long chain called palmitate
40
Activation and conversion of Palmitate
Activated to Palmitoyl CoA | Converted to TAG in the liver
41
De-saturation of Fatty Acyl CoA | location, molecular requirements, restrictions
Occurs in endoplasmic reticulum Requires NADH, O2, and cytochrome b5 Some cannot be synthesized, so must be obtained from diet Omega 3 fatty acids (ω 3 FA) and Omega 6 fatty acids (ω 6 FA)
42
Synthesis of TAG and VLDL
Occurs in the liver and adipose tissue using G3P from glycerol or DHAP
43
Lipoprotein lipase (LPL)
Delivers of VLDL TAGs. Cleaves TAG into FA and glycerol
44
Km of muscle LPL
Has a low Km. Allows it access to fuel source even when levels are low
45
Km of adipose LPL
Has a high Km. Will only work in fed state (storage)
46
Fasting – Adipocytes Release FA
When insulin is low, adipocytes will break down their stores of TAGs into FAs and glycerol Hormone sensitive lipase
47
Glycerophospholipids and Sphingolipids are lipids that aren't used for fuel. What other functions do they have?
``` Cell membranes (phosphatidyl choline, etc) Signaling molecules (PIP2, arachidonic acid, etc) Myelin sheath (sphingomyelin) ```
48
Synthesis of Glycerolipids
Glycerol 3-P + 2 activated FAs form phosphatidic acid Hydrophilic head-groups are added to third carbon of the glycerol Polar uncharged OR charged
49
Degradation of Glycerophospholipids
Phospholipases in cell membrane or lysosomes degrade glycerophospholipids
50
Cholesterol synthesis: Part 1
Synthesis of mevalonate from acetyl-CoA | Committed and rate limiting step
51
Cholesterol synthesis: Part 2
3 phosphates are added to mevalonate to activate it Forms activated isoprenes (5 carbons) isomers
52
Cholesterol synthesis: Part 3
Six of these activated isoprenes are condensed to eventually form Squalene
53
Cholesterol synthesis: Part 4
Forming ring structures from the squalene
54
VLDLs transport
Transport endogenous fats | Liver to peripheral (muscle, adipose)
55
IDLs transport
Remnants of VLDLs not taken up by the liver | Still contain some TAGs and cholesterol
56
LDLs transport
low density lipids After some TAGs removed from IDL (usually to liver) Rich in cholesterol Deliver to liver (~60%) Deliver to adrenocortex, gonads, etc (steroid synthesis)
57
HDL and Reverse Cholesterol Transport
Maturing HDLs are picking up cholesterol of tissues To prevent it from diffusing back to the tissues, LCAT within the HDL will convert it to a cholesterol ester, thus trapping it inside the HDL HDL will then deposit the excess cholesterol back to the liver
58
Cholesterol ester transfer protein (CETP)
mediates the swapping of TAGs with cholesterol esters between VLDLs and HLDs
59
Apoproteins function
serve as receptor ligands/directing to specific tissues
60
maturation of HDLs
Accumulate phospholipids and cholesterol from vascular endothelial lining Fills the empty inner core of the nascent HDL, becomes more round = mature HDL