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PROGRAM KBK
FK-UKI
REFERENCES
Lipids
Lipids include oils, fatty acids, waxes, steroids
triacylglycerol (TAG)
FA-transport protein-4 (FATP4).
bile salts (BS)
cholesterol (CL)
FA-transport protein-4 (FATP4).
acyl-CoA:cholesterol acyltransferase (ACAT)
chylomicrons (CM)
phospholipids (PLs)
Fatty acid transferase (FAT=CD36)
lysophosphatidic acid (LPA)
intestinal FA-binding protein (IFABP)
glycerol-3-phosphate acyltransferase (GPAT)
cholesterol esters (CE).
microsomal triglyceride transfer protein (MTP),
B. FAs and MAG enter the enterocytes by passive diffusion and are
facilitated by transporters, such as intestinal FA-binding protein
(IFABP), CD36 and FA-transport protein-4 (FATP4).
They are then re-esterified sequentially inside the
endoplasmic reticulum by MAG acyltransferase (MGAT) and
diacylglycerol acyltransferase (DGAT) to form TAG.
Phospholipids from the diet as well as bile - mainly LPA - are
acylated by 1-acyl-glycerol-3-phosphate acyltransferase
(AGPAT) to form phosphatidic acid (PA), which is also
converted into TAG.
Dietary CL is acylated by acyl-CoA:cholesterol
acyltransferase (ACAT) to cholesterol esters (CE).
Facilitated by microsomal triglyceride transfer protein (MTP),
TAG joins CE and apolipoprotein B (ApoB) to form
chylomicrons (CM) that enter circulation through the lymph
FFAs that are released from lipoprotein chylomicrons and very-lowdensity lipoprotein (VLDL) catalysed by lipoprotein lipase (LPL)
enters the adipocytes through both passive diffusion and active
transport. Intracellular FFA is first converted to acyl-CoA by acyl-CoA
synthase (ACS), and is then used as a substrate by two parallel TAGsynthetic pathways in the (ER).
Nascent lipid droplets that are generated from the ER are coated
by at least one of the PAT family proteins (which includes
perilipin (PER), adipose differentiation-related protein (ADRP)
and tail-interacting protein of 47 kDa (TIP47)) and S3-12,
whereas mature lipid drops are mainly coated with perilipin.
The mechanism by which other PAT proteins are replaced with
perilipin is unclear. The relative rate of lipogenesis and lipolysis
is determined by nutritional states and is regulated by endocrine
factors, such as catecholamines and insulin, which impose their
effect by the phosphorylation of perilipin and hormonesensitive lipase (HSL).
The phosphorylation of perilipin allows HSL to access lipid
droplets, which results in the hydrolysis of TAG to FFAs that
are then released from the adipocytes. PA, phosphatidic acid;
PKA, protein kinase A; LPA, lysophosphatidic acid.
monoglyceride (MG)
chylomicron (CM)
lipoproteins (LPs)
GLUT
SCD
CPT
PDC
GYG1
MUFAs
: Glucose transporter
: Stearoyl-CoA desaturase
: carnitine palmitoyl transferase
: pyruvate dehydrogenase complex
: glycogenin 1
: monounsaturated fatty acid
cytosol
mitokondria
Lehninger. 2000
CHOLESTEROL
Biosynthesis of
Cholesterol
Regulating Cholesterol
Synthesis
Lipoprotein
Classification of Lipoprotein
A.
High
LDL import
to the cell
Level (mg/dL)
Level mmol/L
Interpretation
< 100
< 2.6
100 to 129
2.6 to 3.3
130 to 159
3.3 to 4.1
160 to 189
4.1 to 4.9
> 190Very
> 4.9
Level mmol/L
<40
< 1.03
4059
1.031.52
>60 disease
>1.55
Interpretation
Low HDL cholesterol, heightened
risk for heart disease, < 50 is the
value for women
Medium HDL level
High HDL level, optimal condition
considered protective against heart
Obesity
Musculoskeletal:
Gaucher disease
Gaucher disease is the most common of the lipid storage
diseases.
It is caused by a deficiency of the enzyme
glucocerebrosidase.
Fatty material can collect in the spleen, liver, kidneys, lungs,
brain, and bone marrow.
Gaucher disease has three common clinical subtypes:
o
Niemann-Pick disease
Niemann-Pick disease is actually a group of autosomal
recessive disorders caused by an accumulation of fat and
cholesterol in cells of the liver, spleen, bone marrow,
lungs, and, in some patients, brain, because of
sphingomyelinase deficiency.
Neurological complications may include ataxia,eye
paralysis, brain degeneration, learning problems,
spasticity, feeding and swallowing difficulties, slurred
speech, loss of muscle tone, hypersensitivity to touch, and
some corneal clouding.
A characteristic cherry-red halo develops around the center
of the retina in 50 % of patients.
Fabry disease
Farbers disease
Krabb disease
Krabb disease (also known as globoid cell leukodystrophy and
galactosylceramide lipidosis) is an autosomal recessive disorder
caused by deficiency of the enzyme galactosylceramidase.
The disease most often affects infants, with onset before age 6
months, but can occur in adolescence or adulthood. The buildup of
undigested fats affects the growth of the nerves protective myelin
sheath and causes severe degeneration of mental and motor skills.
Other symptoms include muscle weakness, hypertonia (reduced
ability of a muscle to stretch), myoclonic seizures (sudden, shocklike contractions of the limbs), spasticity, irritability, unexplained
fever, deafness, optic atrophy and blindness, paralysis, and
difficulty when swallowing. Prolonged weight loss may also occur.
The disease may be diagnosed by its characteristic grouping of
certain cells, nerve demyelination and degeneration, and destruction
of brain cells. In infants, the disease is generally fatal before age 2.
Patients with a later onset form of the disease have a milder course
of the disease and live significantly longer.
Metachromatic leukodystrophy
Metachromatic leukodystrophy, or MLD, is a group of disorders
marked by storage buildup in the white matter of the central
nervous system and in the peripheral nerves and to some extent in
the kidneys
Similar to Krabb disease, MLD affects the myelin that covers
and protects the nerves. This autosomal recessive disorder is
caused by a deficiency of the enzyme arylsufatase A. Both males
and females are affected by this disorder.
The most common form of the disease is late infantile, with onset
typically between 12 and 20 months following birth. Infants may
appear normal at first but develop difficulty in walking and a
tendency to fall, followed by intermittent pain in the arms and
legs, progressive loss of vision leading to blindness,
developmental delays, impaired swallowing, convulsions, and
dementia before age 2.
Death generally occurs within 6 to 14 years after onset of
symptoms.
Wolmans disease
Wolmans disease, also known as acid lipase deficiency, is
a severe lipid storage disease that is usually fatal by age 1.
This autosomal recessive disorder is marked by
accumulation of cholesteryl esters (normally a transport
form of cholesterol) and triglycerides (a chemical form in
which fats exist in the body) that can build up significantly
and cause damage in the cells and tissues
Both males and females are affected by this severe
disorder. Infants are normal and active at birth but quickly
develop progressive mental deterioration, enlarged liver
and grossly enlarged spleen, distended abdomen,
gastrointestinal problems including steatorrhea (excessive
amounts of fats in the stools), jaundice, anemia, vomiting,
and calcium deposits in the adrenal glands, causing them to
harden.