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Health Maintenance and Management A

Biochemistry
Lipids
Dietary purposes

Purposes once absorbed

Essential fatty acids


Concentrated food energy
Fat-soluble vitamins
Satiety (slow gastric
emptying)

Purposes of fats in the body


Triglycerides
Phospholipids
Steroids Cholesterol
Cholesteryl ester
Important groups of lipids
Mouth
Stomach
Small
intestine

Storage
Emergency fuel
Organ protection
Insulation
Cell membranes
Conversion to other compounds

Function

Nature

Storage compound inside cells


Cell membrane compound (forms bilayer)
Cell membrane compound (provides rigidity)
Storage compound inside cells

Neutral
Polar
Polar
Neutral

Substrate

Enzyme/Acid

Product

Medium-chain
triglycerides (mainly)
Medium-chain
triglycerides (mainly)
Triglycerides
Emulsified triglycerides

Lingual lipase

Smaller-chain-triglycerides

Gastric lipase

Smaller-chain triglycerides

Bile acids
Pancreatic lipase

Free fatty acids and


monoglycerides

(Formed
spontaneously)

Emulsified triglycerides
Free fatty acids and
monoglycerides
Micelles

Stages in lipid processing and digestion

Micelles transported across mucous membrane of intestinal villi into enterocytes


(dissolution or passive transport).
Lipid transport:
Small lipids (C4-C12) absorbed directly into bloodstream.
Large lipids (>C12) packaged into chylomicrons, released into lymphatics,
then transported to tissues via bloodstream (to be stored as adipose tissue or
used by muscle).

Matt Schiller

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Health Maintenance and Management A

Biochemistry
Lipoproteins
Lipoprotein Structure

Core

Surface

Nature
Neutral
Contents Triglyceride

Polar
Apoproteins (provide structure)
Cholesteryl esters Phospholipids (emulsifiers)
Free cholesterol

Lipoprotein Classes and Metabolism

Endogenous

Exogenous
(dietary)

Description
Chylomicron

Transport dietary triglyceride from gut to


liver, adipose tissue, and muscle
Chylomicron
Derived from chylomicrons after extraction of
remnant
triglyceride by lipoprotein lipase and
metabolised by liver
Very low density
Transport mostly triglyceride and some
lipoprotein (VLDL)
cholesterol from liver to periphery
Intermediate density Transient lipoprotein, derived from VLDL after
lipoprotein (IDL)
extraction of triglyceride by lipoprotein lipase
Low density
Derived from IDL after extraction of
lipoprotein (LDL)
triglyceride by hepatic lipase
High density
Involved in reverse transport of cholesterol
lipoprotein (HDL)
from cells to liver

Major lipid
content
Dietary
triglyceride
Dierary
cholesterol
Endogenous
triglyceride
Endogenous
cholesterol
Endogenous
cholesterol
Cholesterol

Lipoprotein classes

Lipoprotein metabolism

Matt Schiller

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Health Maintenance and Management A

Biochemistry
Hypercholesterolaemia
LDL receptors in liver perform LDL uptake and maintain blood cholesterol levels.
If LDL receptors are defective (e.g. genetic defect), hypercholesterolaemia occurs.
Saturated fats lead to a decrease in LDL receptor numbers.
Low HDL compounds the risk of high LDL.
LDL-HDL ratio is a good indicator of heart disease risk (better than total cholesterol).
HDL Levels
Raises Lowers
Alcohol
Exercise
Obesity
Diabetes
Smoking
Oestrogen
Androgens/ Progesterone
Dietary Saturated Fat
Dietary Polyunsaturated Fat

LDL Levels
Raises Lowers

Conditions that alter levels of HDL and LDL

Cellular Cholesterol Homeostasis and Cholesterol Biosynthesis


Cholesterol is essential for bile acid and steroid hormone production, as a cell
membrane constituent, and for cell signalling.
Cholesterol excess results in the formation of atherosclerotic plaques.
If cholesterol content is too low, cholesterol uptake and biosynthesis are both
increased, and vice versa.
At least 18 steps in cholesterol biosynthesis are down-regulated by cholesterol itself.
Reduction of hydroxylmethylglutaryl coenzyme A (HMG-CoA) by HMG-CoA reductase is
the committed irreversible step in cholesterol biosynthesis and is controlled at multiple
levels (statins are HMG-CoA reductase inhibitors).
Acetate

Hydroxymethylglutaryl Coenzyme A (HMG-CoA)

Reducation

HMG-CoA
Reductase

Biosynthesis

Mevalonate

Uptake
LDL Receptor

Cholesterol

Negative
Feedback

Negative
Feedback

Summary of cellular cholesterol homeostasis


Matt Schiller

Page 3 of 7

Health Maintenance and Management A

Biochemistry
LDL and Atherosclerotic Plaque Formation
If LDL concentrations exceed clearing ability of liver, then likelihood of cholesterol
deposition in artery walls is increased.
LDL undergoes a modifications that allows it to be taken up by cells of the vascular
wall in an uncontrolled fashion.
Modified LDL is taken up by macophages, which then become foam cells (hallmark of
early atherosclerosis).

Cholesterol transport and atherosclerotic plaque formation


Reverse Cholesterol Transport and Atherosclerotic Plaques
HDL transports cholesterol from foam cells to liver (for eventual secretion).
Apoprotein A1 (ApoA1) is the major HDL apoprotein and is involved in taking lipid from
foam cells in reverse cholesterol transport.
Apoprotein A1
(from intestine)

Foam Cell
Lipid Droplets

HDL

Other steps

Liver

Bile acids, biliary cholesterol

Basic steps in reverse cholesterol transport

Matt Schiller

Page 4 of 7

Health Maintenance and Management A

Biochemistry
Oxidative Stress
Reactive Oxygen Species
Electron structure of oxygen favours reduction in single electron steps:
Slows direct combination of oxygen with organic compounds.
Allows cells to oxidise fuels and gain energy in a slow controlled manner.
Results in generation of reactive oxygen species.
Reactive oxygen species (ROS) oxygen metabolites produced by one-electron
reduction, being intermediates between molecular oxygen and water.
Oxidative stress the accumulation of ROS due to production occurring at a faster rate
than removal by cellular defence mechanisms.
Ischaemia and reperfusion injury are associated with free-radical injury.

Main ROS and the steps involved in their formation


ROS Formation
Hydrogen peroxide (H2O2) deliberate product of the reactions catalysed by some
oxidase enzymes (mainly metabolic).
Cytochrome P450 enzymes important for unwanted compound removal; leak free
radicals.
Superoxide (O2) produced by the respiratory chain (leakage effect), particularly at
coenzyme Q.

Reactions involving spontaneous formation of hydroxyl free radicals from hydrogen


peroxide and superoxide

Factors that increase ROS formation include radiation, inflammation, ageing, high
oxygen concentrations, air pollutants, and certain chemicals and drugs.

Matt Schiller

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Health Maintenance and Management A

Biochemistry
Lipid Peroxide Chain Reaction
Causes damage to cell membranes (affecting permeability) via a chain reaction:
Polyunsatyurated lipid (LH) reacts with superoxide to produce lipid radical (L).
L reacts with oxygen to produce lipid peroxy-radical (LOO).
LOO reacts with another LH to produce lipid peroxide and regerate L.
Process repeats, allowing one free radical to convert a large amount of LH to
LOOH.
Spontaneous degradation of LOOH occurs due to its instability, forming
malondialdehyde and other compounds.
Termination of chain reaction occurs when L and LOO react (uncommon).

Lipid peroxide chain reaction (left), termination of reaction (middle) and degradation of
LOOH (right)
Cellular ROS Damage

Matt Schiller

Page 6 of 7

Health Maintenance and Management A

Biochemistry
Ischaemia and Reperfusion Injury
Reperfusion injury where damage to ischaemic tissue increases when blood supply is
restored, believed to result from ROS formation when oxygen is restored to hypoxic
cells.
Damage from reperfusion injury can be greater than that from preceding ischaemia.

Ischaemia

Reperfusion

Decreased ability to remove ROS


Decreased ROS production
Two above changes reactions cancel
each other

ROS production immediately resumed


(transient burst of ROS formation)
ROS removal remains compromised for a
period

Changes to ROS activity during ischaemia and reperfusion


Cellular Defences Against ROS
Antioxidant scavenging enzymes (e.g. superoxide dismutase, catalase, glutathione
peroxidise, glutathione reductase) enzymes that prevent ROS formation and
encourage formation of other substances from ROS.

Mechanisms of antioxidant scavenging enzymes

Mechanism
Primary/Secondary
antioxidant
Vitamin antioxidants

Matt Schiller

Vitamin E
(tocopherols)

Vitamin C (ascorbate)

Carotenoids

Protects against lipid


peroxidation in
membranes
Primary (no other
functions)

Acts as a free-radical
scavenger in aqueous
environments
Secondary (other
function)

May protect lipids


against
peroxidation
Secondary

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