Lipid And Amino Acid Metabolism Flashcards

1
Q

Chapter 11

A
  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
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2
Q

Components of Dietary Fat

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

Emulsification

A

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

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4
Q

Fat Digestion
Micelle Formation
Fat Absorption

A

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

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5
Q

Bile

A

Compound secreted from the liver and stored in the gall-bladder that is composed of:

         1. bile salt
         2. Cholesterol
         3. Pigments
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6
Q

Micelles

A

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.

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7
Q

Lacteals

A

Vessels of lymphatic system

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8
Q

Thoracic Duct

A

A lymphatic duct that empties into the subclavian vein

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9
Q

Lipid Mobilization Inducing Factors

A
  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**
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10
Q

Albumin

A

Proteins that carries free fatty acids in the blood stream

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11
Q

Lipid Transport Range

A

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***

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12
Q

Lipoproteins

A

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
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13
Q

Apolipoproteins

A
  • –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
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14
Q

Types and Functions of Apolipoproteins

A

—-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

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15
Q

LCAT

A

Enzyme that catalyzes cholesterol esterification

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16
Q

Cholesterol Sources

A
  1. HDL
  2. LDL
  3. De novo synthesis
17
Q

De Novo Synthesis of Cholesterol

A
  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
Q

Cholesterol Transport Involved Enzymes

A
  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
Q

Fatty Acids

A
  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
Q

Omega Numbering System

A

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
Q

Nontemplate Synthesis

A

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

22
Q

Citrate Shuttling of Acetyl-CoA

A

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
Q

Triacylglycerol Synthesis

A
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
Q

Types of Fatty Acid Oxidations

A
  1. Beta-oxidaion in mitochondria
  2. Peroxismal Beta-Oxidation
  3. Alpha-oxidation—–specific to branched chains
  4. Omega-oxidation in the ER
25
Q

Ketogenesis

A
  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
Q

Ketolysis

A

**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
Q

Succinyl-CoA Acetoacetyl-CoA Transferase

A

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

28
Q

Enzymes Involved in Protein Metabolism

A
1. Stomach: 
               I. Pepsin
2. Pancreatic: 
               1. Trypsin
              2. chymotrypsin
              3. carboxypeptidase A & B
3. Intestinal brush border enzymes: 
              1. dipeptidase
              2. aminopeptidase
29
Q

Protein Catabolism

A
  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
Q

Types of Amino Acids

A
  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