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Fatty Acids and Lipids
The various types of lipids
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Fatty acids
Triglycerides (which are 3 fatty acids bound to glycerol)
Phospholipids (glycerol, 2 fatty acids, phosphate and something like choline)
Sterols (cholesterol and its family of derivatives, including bile acids)
Fatty acid oxidation and synthesis
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Ketone Bodies
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Cellular lipids
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All your fatty acids end up broken down to Acetyl-CoA which ends up being used in Krebs cycle
The energy yield from this is enormous.
The steps involved are sequential removal of 2 carbon atoms from the fatty acid chain, and this
whole process is called BETA-OXIDATION; after it you end up with Acetyl-CoA
The catabolism of 1 mol of a 6-carbon fatty acid at the end of the Krebs Cycle yields 44 mol ATP
In most tissues the acetyl-CoA condenses to form acetoacetyl-CoA.
The liver contains a deacylase, and instead free acetoacetate is formed
Free acetoacetate gets converted into beta-hydroxybutyrate and acetone.
The liver has no mechanism to deal with them, and they diffuse into the bloodstream.
Acetoacetate, beta-hydroxybutyrate and acetone are ketone bodies.
Outside the liver, the tissues Do have a mechanism to deal with the ketones. They transfer CoA to
them from succynil-CoA and thereby employ them in Krebs cycle, using them to make ATP.
Normally, ketones are used as quickly as they are synthezised in the liver, and blood levels are
very low.
However if there aren’t enough products of glucose metabolism around to fit into Krebs cycle,
Acetyl-CoA accumulates, more of it gets condensed into acetoacetyl-CoA, and the liver pumps
out excessive amounts of the ketone bodies.
The tissues have only a limited capacity to oxidize the ketones, and they accumulate in the
bloodstream; seeing as acetoacetate an beta-hydroxybutyrate are anions of moderately strong
acids, they soon surpass the buffering capacity of the blood, and acidosis develops.
Two main forms; structural lipids and NEUTRAL FAT (which is adipose tissue)
In non-obese individuals, the neutral fat forms 15% of body weight in men and 21% in women
This neutral fat is synthesized from glucose (which gets metabolized into fatty acids)
There is also BROWN FAT which is a small percentage of the total body fat, and is found mainly
in children.
 This brown fat is located between the scapulas, at the nape of the neck, and along the
greater vessels.
 Brown fat enjoys a rich sympathetic innervation, and contains a particular uncoupling
protein in the mitochondria which causes the metabolic function to be uncoupled from
ATP production, and rerouted to the generation of heat.
Plasma lipids and lipid transport
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Obviously, the major lipids are insoluble in the watery goo of the plasma.
Free fatty acids circulate bound to ALBUMIN
Cholesterol, triglycerides and phospholipids circulate bound to LIPOPROTEINS
There are 6 types, classified according to size and lipid content
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CHYLOMICRONS which originate in the intestine and are the largest
CHYLOMICRON REMNANTS which originate in the capillaries
VLDL which originate from the liver
Intermediate density lipoproteins which originate from VLDL
LDL which originate from IDL
HDL which originate from LDL
HDL have the most protein and LDL have the most cholesterol
This document was created by Alex Yartsev ([email protected]); if I have used your data or images and forgot to reference you, please email me.
Free Fatty Acid Metabolism
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Free fatty acids are a major source of energy to numerous tissues
Some are absorbed by cells from the bloodstream, and others are synthesized from fat depots
They are used extensively in the heart, but pretty much any tissues can use them.
There are two main enzymes involved:
LIPOPROTEIN LIPASE:
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from the endothelium of capillaries, hydrolyses the triglycerides in the
chylomicrons and VLDL, thus producing free fatty acids and glycerol,
which the cells then reassemble into triglycerides.
Thus lipoprotein lipase is a FATTENING enzyme. It fattens you. Its activity
is inhibited by fasting and stress, and activated by feeding.
o HORMONE-SENSITIVE LIPASE
an enzyme of adipose tissue, which catalyses the breakdown of stored
triglycerides and causes the adipose tissue to release free fatty acids into the
bloodstream.
Its activity is triggered by starvation and stress; it is inhibited by feeding and
insulin. It is a DIETING enzyme.
ESSENTIAL FATTY ACIDS
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- LINOLENIC, LINOLEIC, and ARACHIDONIC
Polyunsaturated fatty acids which are essential to humans.
Precursors of eicosanoids: products of eicosa (20-carbon) – polyunsaturated acids
On this, relies the synthesis of all those prostaglandins and leukotrienes
CHOLESTEROL METABOLISM
Most dietary cholesterol comes from egg yolk and animal fat.
Dietary cholesterol
Dietary Triglycerides
Some cholesterol which is
excreted as bile acids is
reabsorbed from the intestine
HMG-CoA reductase:
A rate-limiting enzyme in the pathway of DE-NOVO
CHOLESTEROL SYNTHESIS: i.e. when dietary cholesterol
intake is low, HMG-CoA Reductase will synthesise the extra
cholesterol.
Cholesterol has negative feedback: rising dietary cholesterol
will inhibit HMG-CoA. STATINS also inhibit HMG-CoA
triglycerides are discharged
at the capillary endothelium
The Liver
Incorporated
into
chylomicrons
The liver collects the returning
cholesterol and synthesizes
some of its own
Some cholesterol is
excreted in bile, in
free form as well as
in bile acid form
Cholesterol ends up being dragged back
into the liver in the chylomicron remnants
Returns to the liver as HDL
Repackaged as VLDL, the cholesterol
returns to the circulation
References: Ganong's Review of
Medical Physiology, Chapter 1