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Flashcards in Lipid And Amino Acid Metabolism Deck (30):
1

Chapter 11

1. Lipid Digestion and Absorption
2. Lipid Mobilization
3. Lipid Transport
4. Cholesterol Metabolism
5. Fatty acids and triacylglycerols
6. Ketone bodies
7. Protein Catabolism

2

Components of Dietary Fat

1. Triacylglycerols
2. Cholesterol
3. Cholesteryl Esters
4. Phospholipids
5. Fatty Acids

3

Emulsification

Process of fat digestion in the duodenum where fat and water, 2 immiscible compounds, mix to form an emulsion that has greater surface area for enzymatic activity

4

Fat Digestion
Micelle Formation
Fat Absorption

A. Digestion
1. Minimal in the mouth
2. Major in the duodenum
I. Emulsion forms
II. Acted on by:
1. Bile
2. Pancreatic Enzymes:
I. Lipase
II. Colipase
III. Cholesterol Esterase
***Fat Digestion Products******
1. 2-monoacylglycerol
2. free fatty-acids
3. cholesterol
B. Micelle Formation
1. Fat digestion products and bile form micelles
C. Absorption
1. Micelles diffuse along the brush border of
intestinal mucosal cells for absorption
2. Digested lipids pass the brush border and get
absorbed into the mucosa
3. Digested lipids re-esterify to form triacylglycerol
and cholesteryl esters
4. Triacylglycerol and cholesteryl esters combine
with apoproteins and fat-soluble vitamins to form
chylomicrons
5. Chylomicrons leave the intestine via lacteals
6. Chylomicrons then enter the bloodstream via the
thoracic duct

5

Bile

Compound secreted from the liver and stored in the gall-bladder that is composed of:
1. bile salt
2. Cholesterol
3. Pigments

6

Micelles

Amphipathic compounds, composed of 2-monoacylglycerol, cholesterol, fatty acids and bile salts, that are essential to fat digestion, transport and absorption along the length of the small intestine.

7

Lacteals

Vessels of lymphatic system

8

Thoracic Duct

A lymphatic duct that empties into the subclavian vein

9

Lipid Mobilization Inducing Factors

1. HSL [Hormone-Sensitive-Lipase]
I. Activated by:
1. Epinephrine
2. Cortisol
3. Falling Insulin level
4. Elevated Glucagon ???
II. Function:
1. Hydrolysis of adipose tissue's
triacylglycerol into
I. Free fatty Acids
II. Glycerol
2. LPL [Lipoprotein Lipase]
I. Activated by: Hormones indicated above
II. Function:
1. Metabolism of:
I. Chylomicrons
II. VLDL [very low density
lipoproteins]
****LPL releases free fatty acids from lipoproteins******

10

Albumin

Proteins that carries free fatty acids in the blood stream

11

Lipid Transport Range

Lipids can be transported in the bloodstream as either
1. free fatty acids with the help of albumin
or as 2. lipoproteins


****Cholesterol and triacylglycerol are carried in the blood stream as lipoproteins*******

12

Lipoproteins

I. Identity:
1. Aggregates of apolipoproteins and lipids
produced by the intestine and liver that
differ depending on their lipid:protein ratio &
density and that trasport lipids to various tissues
II. Types with increasing density & protein:lipid ratio :
1. Chylomicrons
I. assembly of cholesterol, cholesteryl
ester, triacylglycerol & apolipoproteins
produced in the small intestine
II. soluble in both lymphatic and blood
vessels
2. VLDL [very low density lipoproteins]
I. Assembly of triacylglycerol and fatty
acids produced in the liver
Note. its fatty acid is synthesized
from excess glucose
3. IDL [intermediate density lipoprotein]
I. Assembly of VLDL without
triacylglycerols
****AKA VLDL remnant*****
II. Transition particle b/w
[VLDL/chylomicrons] & [LDL &HDL]
III. Either absorbed by apolipoproteins in
the liver or further processes in the
blood stream to form LDL by taking
cholesterol ester from HDL
4. LDL [low density lipoprotein]
I. Assembly of cholesterol transported to
tissues
II. Transports cholesterol to tissues for
1. biosynthesis of
I. steroid hormones
II. cell membrane
III. bile
IV. vitamin D
III. Bad Cholesterol with higher lipid:protein
ratio
5. HDL [high density lipoprotein]
I. Assembly of cholesterol and
apolipoproteins synthesized in the liver
and small intestine
II. Transports
1. cholesterol to steroidogenic tissues
2. apolipoprotein to some other
lipoproteins
III. Good cholesterol b/c it carries
apolipoprotein

*****Note********
1. Chylomicron and VLDL are triacylglycerol transporters
2. LDL & HDL are cholesterol transporters

13

Apolipoproteins

---aka apoproteins
---protein component of lipoproteins that participate in
1. cell-signalling
2. cell-reception
3. cholesterol recovery
----Types:
1. apoA-I
2. apoB-48
3. apoB-100
4. apoC-II
5. apoE

14

Types and Functions of Apolipoproteins

----Types:
1. apoA-I
I. activates LCAT
2. apoB-48
I. mediates chylomicron secretion
3. apoB-100
I. permits uptake of LDL by the liver
4. apoC-II
I. activates lipoprotein lipase
5. apoE
I. permits uptake of chylomicron
remnants and VLDL by the liver

15

LCAT

Enzyme that catalyzes cholesterol esterification

16

Cholesterol Sources

1. HDL
2. LDL
3. De novo synthesis

17

De Novo Synthesis of Cholesterol

1. Location:
I. Liver
2. Reactants:
I. Mitochondrial Acetyl-CoA transported to the
cytoplasm by Citrate Shuttle
II. ATP
III. NADPH [from the pentose phosphate pathway]
3. Rate-Limiting Step
I. Synthesis of mevalonic acid in SER which is
catalyzed by HMG CoA Reductase
4. Regulatory Mechanisms:
I. levels of cholesterol
II. levels of insulin
****High levels, ---->stimulates pathway
III. HMG-CoA reductase gene expression

18

Cholesterol Transport Involved Enzymes

1. LCAT
I. found in the bloodstream
II. activated by apoA-I
III. adds a fatty acid to cholesterol to produce a
soluble cholesteryl ester
****found in HDL****
2. CETP [cholesteryl-ester-transport-protein]
I. enzyme that facilitates transport of cholesteryl
ester from HDL to IDL in the bloodstream for
LDL creation

19

Fatty Acids

1. Chemical Identity
I. Chains of carboxylic acids that form micelles
****can be esterfied to other compounds****
****can form salts**********************************
2. Nomenclature
I. number of carbons: number of double bonds
1. saturated vs. unsaturated
II. description of double bond positioning and
isomerism
1. using the omega numbering system
***ex: [18:2 cis,cis-9,12)
3. Synthesis
1. Location
I. Cytosol of hepatocytes
2. Reactants:
I. Acetyl-CoA
I. Transported from the mitochondrial
inner membrane to the cytosol by
citrate shuttle
3. Enzymes:
1. Acetyl-CoA Carboxylase
I. Enzyme that activates Acetyl-CoA by
adding CO2 to it to form malonyl-CoA
II. Activated by elevated insulin and citrate
III. Requires biotin and ATP for functioning
2. Acetyl-CoA Synthase
I. AKA palmimate synthase
II. Complex enzyme with ACP/acyl-carrier
protein
III. Requires:
1. 8 Acetyl-CoA
2. Pantothenic Acid
3. NADPH
4. Steps:
1. Attachment of palmimate synthase to an
ACP
2. Bond formation b/w malonyl-CoA/ACP &
growing chain
3. Reduction of carboxyl group
4. Dehydration
5. Reduction of a double bond
*****Repetition until generation of 16
molecule palmimate*****
5. Product:
I. Palmitic acid or Palmitate
1. Taken up to adipose tissue for storage
4. Beta-Oxidation
I. Location:
I. Mitochondria
II. Process:
I. Activation of fatty acid by attachment of a
CoA to it to form a fatty acyl-CoA
****Process is catalyzed by fatty acyl-
coa-synthatase
II. Transport of fatty acids into Mitochondria
1. Short and medium chains diffuse
freely
2. Long chains [14-20] transport via
a carnitine shuttle
3. Very long chains [20+] get oxidized
elsewhere in the cell
*****Rate Limiting Step******
III. Beta Oxidation in Mitochondria
1. Cyles of 4 steps
1. oxidation of the fatty acid to
form a double bond
2. Reduction of the double bond to
form a hydroxyl group
3. oxidation of the hydroxyl group
to form a carbonyl group
4. Division of the carbonyl
[ketoacid] into an acyl-CoA and
an acetyl-CoA
****************Cycle repeats until 1 acetyl-CoA is left********
2. Products:
I. 1 Acetyl-CoA
***Fate:
1. in the muscle and
adipose tissue, enter
citric acid cycle
2. in liver, start
gluconeogenesis
or 3. make ketone bodies
II. 1 NADH & 1 FADH2
****Fate:
1. get oxidized in ETC

20

Omega Numbering System

A fatty acid nomenclature method used to indicate
1. the position of the last double bond relative
to the end of the chain
2. the major fatty acid precursor

******pg. 373*****Review

21

Nontemplate Synthesis

Synthesis that does not rely on the genetic code like that of carbohydrates and lipids
********protein and nucleic acid synthesis is not included******

22

Citrate Shuttling of Acetyl-CoA

Transport of Citrate from the inner mitochondrial membrane to the cytosol of hepatocytes where citrate lyase can splice citrate into acetyl-CoA and OAA to provide adequate supply of acetyl-CoA for fatty acid synthesis

****This process occurs following a big meal when the citric acid cycle slows down due to presence of sufficient energy supplies****

23

Triacylglycerol Synthesis

1. Location
I. Liver
II. Adipose Tissues
2. Process
I. Attachment of glycerol-3-phosphate to 3 fatty
acids

***Triacylglycerol synthesized in the liver get transported to the adipose tissues as VLDL

24

Types of Fatty Acid Oxidations

1. Beta-oxidaion in mitochondria
2. Peroxismal Beta-Oxidation
2. Alpha-oxidation-----specific to branched chains
3. Omega-oxidation in the ER

25

Ketogenesis

1. Ketogenesis:
I. Location:
1. Mitochondria of hepatocytes
II. Reactant:
1. Excess/accumulated acetyl-CoA from
B-Oxidation
III. Steps:
1. activation of the pathway by
accumulated acetyl-CoA from both B-
Oxidation and slowed citric acid cycle
2. HMG-CoA formation by HMG-CoA
synthase
3. HMG-CoA break-down to acetoacetate
by HMG-CoA lyase
4. Acetoacetate conversion to
B-hydroxybutyrate
***************Byproduct of acetone will also be formed*****
IV. Products:
1. acetoacetate
2. B-hydroxybutyrate


****Used during extended periods of fasting and starvation****

26

Ketolysis

*******Liver cannot catabolize the ketone bodies it produces**********

Steps:

1. Mitochondria picks up acetoacetate from the bloodstream and activates it with the help of succinyl-CoA Acetoacetyl-CoA transferase/or thiophorase

2. In this process, 3-hydroxybutyrate gets oxidized to acetoacetate


V. Types of Metabolizing Tissues:
1. cardiac muscle
2. skeletal muscle
3. renal cortex
4. cerebral tissue [after a week when
bloodstream is filled
with ketone bodies]

****Occurs during extended periods of fasting and starvation*****

27

Succinyl-CoA Acetoacetyl-CoA Transferase

----AKA thiophorase
----enzyme outside of the liver that oxidzes
3-hydroxybutyrate to acetoacetate in ketolysis

28

Enzymes Involved in Protein Metabolism

1. Stomach:
I. Pepsin
2. Pancreatic:
1. Trypsin
2. chymotrypsin
3. carboxypeptidase A & B
3. Intestinal brush border enzymes:
1. dipeptidase
2. aminopeptidase

29

Protein Catabolism

1. Site:
1. Muscles
2. Liver
2. Steps
1. metabolism with assistance of enzymes
1. stomach
2. pancreatic
&3. brush border enzymes of the small
intestine
2. transamination of amino-acids
3. Conversion of amino acids into
1. glucose through gluconeogenesis
[if glucogenic]
2. acetyl-CoA & ketone bodies
[if ketogenic]
4. Excretion of the transaminated amine groups
through the urea cycle
3. Products:
1. Amino Acids
2. Dipeptides
3. Tripeptides
4. Absorptive paths
1. Luminal membrane of small intestine
*involves secondary active transport
of amino acids
2. Basal membrane of small intestine
*involves simple diffusion of amino
acids

30

Types of Amino Acids

1. Glucogenic
I. Convert to glucose through
gluconeogenesis
II. Exceptions: lysine & leucine
2. Ketogenic
I. Convert to ketone bodies and acetyl-CoA
II. which ones?
1. lysine
2. leucine
3. isoleucine
4. threonine
5. tryptophan
6. tyrosine
7. phenylalanine