Lipid metabolism

Kepaniteraan Klinik Stase Kardiovaskuler

RST Tk.II Dustira Cimahi
FK Universitas Tanjungpura
Cimahi
2018

Periode 24 September – 20 Oktober 2018

 Topic discussion

• Objectives

– How fatty acids are activated and transported into mito

chondria for oxidation.

– Oxidation of fatty acids.

– Role of lipoproteins in cholesterol metabolism.

 Introduction
• Reserves of stored triglycerides are mobilized as needed for energ
y production.

• Fat mobilization is stimulated by epinephrine. The triglycerides are

hydrolyzed to fatty acids and glycerol and enter the blood stream.

• Glycerol is converted to glycerol- 3 phosphate and then to dihydro

xyacetone phospahte, which enters glycolysis for energy productio
n.

• Free fatty acids are converted to fatty acyl CoA molecules, which a
re broken down to acetyl CoA by beta oxidation. The acetyl CoA m
ay be used for energy production by way of the citric acid cycle an
d the electron transport chain.
 Fatty acid oxidation

Fatty acids are degraded to acetyl CoA

• Fatty acids enter tissue cells in need of energy. Fatty acids mu

st pass through the mitochondrial membrane to be oxidized an
d to produce energy. The passage cannot occur until the fatty
acid is converted to its thioester with CoA. The product of this r
eaction is fatty acyl CoA. The reaction is:

Fatty acid + HS – CoA+ ATP Fatty acyl CoA + AMP + Pi

This is known as activation of fatty acid. Fatty acids must be a

ctivated before they are degraded to produce energy. Fatty aci
ds are activated in the cytosol, but oxidation occurs in the mito
chondria.
 Beta oxidation
• The formation of fatty acyl CoA molecule prepares fatty acids for entry
into the mitochondria. Carnitine helps fatty acly CoA to enter mitochon
dria. There they are degraded in the catabolic process called beta oxi
dation. During beta oxidation, the third (or beta) carbon of the saturat
ed fatty acid chain of the fatty acyl CoA is oxidized to a ketone.

• Beta oxidation is a spiral pathway. Each round consists of four enzym

e-catalyzed steps that yield one molecule of acetyl CoA and an acyl C
oA shortened by two carbons, which becomes the starting substrate f
or the next round. Seven rounds of beta oxidation degrade a C16 fatty
acid to eight molecules of acetyl CoA.

Complete oxidation of one molecule of palmitic acid to carbon dioxide and

water yields 129 molecules of ATP. One round of beta oxidation yields
17 ATP.
Beta Oxidation is regulated by availability of free CoA, by the ratios of NA
D/NADH and Q2/QH.
The reactions of ß oxidation
Ketogenesis
 Cholesterol synthesis
• Synthesis of cholesterol takes place in cytosol.

• The carbon skeleton of cholesterol is formed from a

cetyl CoA. The pathway of cholesterol biosynthesis
has over 30 steps.

• The rate determining step of cholesterol synthesis a

nd the major control point is the conversion of HMG-
COA to mevolonic acid.

• Some intermediate steps of cholesterol synthesis ar

e mevolonic acid— squalene— zymosterol—cholest
erol.
The fate of cholesterol

1. It can be incorporated
into a cell membrane.
2. It may be acylated to f
orm cholesteryl ester
for storage.
3. It is precursor of stero
id hormone (estrogen,
testosterone)
4. It is a precursor of bil
e acids.
 Lipoprotein function

Chylomicrons, which are mostly lipid, transport dietary lipids to the liver and
other tissues. Liver produces triacylglycerol-rich very- low- density lipoprotei
ns (VLDL). As they circulate in the tissues, VLDL give up their triacylglycero
l and become cholesterol-rich low- density lipoproteins (LDL), which are tak
en up by tissues. High Density Lipoproteins transport cholesterol from the ti
ssues back to liver.
 LDL

Cell can synthesize cholesterol as well as obtain it from circulating L

DL. When LDL dock with LDL receptor on the cell surface, the lipopr
otein-receptor complex undergoes endocytosis. Inside the cells, the l
ipoprotein is degraded and cholesterol enters the cytosol. Excess ac
cumulation of cholesterol leads to atherosclerosis.
An atherosclerotic plaque blocking the lumen of an artery
 HDL

HDL are essential for removing excess cholesterol from cells. A transp
orter or flippase moves cholesterol from the cytosolic leaflet to the extr
acellular leaflet, from which it can diffuse into the HDL. Defects in the g
ene of the transporter cause Tangier disease, characterized by accum
ulations of cholesterol in tissues and a high risk of heart attack.
Lipid metabolism in context
Summary of lipid metabolism