LIPID AND

DYSLIPIDEMIA
Ike Dhiah R.
Biochemistry and Molecular Biology
Outline
• Definition

• Triglycerides

• Cholesterol

• Lipoprotein Metabolisms

• Dietar y lipid and Dyslipidemias

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Objectives

Af ter f i n i sh i n g th i s su b j ec t, stu d en ts
sh o u l d b e a b l e to :

• D esc ri b e l i p i d (c h o l estero l a n d
tri g l yc eri d es) i n meta b o l i sm c o n tex t

• D esc ri b e th e c o n tri b u ti n g f a c to rs i n
d ysl i p i d emi a s

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Major Plasma Lipids

CHOLESTEROL TRIGLYCERIDES PHOSPHOLIPIDS

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 LIPOPROTEIN
STRUCTURE

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LIPOPROTEIN CLASSES

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APOLIPOPROTEINS
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Triglycerides Synthesis

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Lipid
Metabolism
Pathway

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 METABOLIC
FATE OF
CHYLOMICRON

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Causes of Hypertriglyceridemia

Familial High Carbohydrate

Hypothyroidism
hypertriglyceridemia diet

Poorly controlled
Nephrotic syndrome Chronic renal failure
diabetes

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 Malabsorption syndrome

Causes of Low Malnutrition

level of
Triglycerides Hyperthyroid

Abetalipoproteinemia

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Chylomicrons
• D e l i ve r TG f r o m G a s t r o i n t e s t i n a l t ra c t t o m u s c l e a n d a d i p o s e
tissue, where Lipoprotein Lipase (LPL) release fatty acid and
g l yc e r o l

• N o l o n g e r TG r i c h : c hy l o m i c r o n r e m n a n t a n d i s d e l i ve r e d t o
l i ve r

• L i ve r e x p o r t c h o l e s t e r o l a n d o t h e r TG i n t h e fo r m o f V L D L i n t o
the circulation

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REGULATION OF
KETOGENESIS

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 FORMATION,
UTILIZATION, AND
EXCRETION OF
KETONE BODIES

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Role of cholesterol
Precursor of all other steroids in the body

Cor ticosteroids

Sex hormones

Bile acids

Vitamin D
 More than half the cholesterol of body
700 mg per day and the remainder is

Synthesis in provided by average diet

the body
Synthesis take places:
Liver
Intestine
Nucleated cells (endoplasmic reticulum and
cytosol)
 1. Synthesis of mevalonate from Acetyl CoA

2. Formation of Isoprenoid units from

mevalonate by loss of CO2

Synthesis of 3. Condensation of six isoprenoid units form

squalene
Cholesterol 4. Cyclization of squalene give rise to the
parent steroid: lanosterol

5. Formation of cholesterol from lanosterol

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 METABOLIC
FATE OF VLDL

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 • TG rich but have a higher
Very-Low cholesterol composition than
chylomicrons
Density
• VLDL undergoes same degradation
Lipoprotein as Chylomicrons via LPL

(VLDL) • LPL activity: VLDL – IDL - LDL

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Low Density Lipoprotein (LDL)

• LDL carries largest portion of cholesterol

• Tissues can take small por tion of LDL that

provides cholesterol for cell membrane and
steroid synthesis

• Liver degrades majority of circulating LDL

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Cellular
Uptake of
Cholesterol

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 Uptake of cholesterol-containing
lipoproteins by receptor
Uptake of free cholesterol from cholesterol-
rich lipoproteins to cell membrane
Cholesterol synthesis
Hydrolysis of cholester yl esters by enzyme
cholester yl ester hydrolase
Cholesterol
balance in tissue
Eff lux of cholesterol from the membrane to
HDL
Esterif ication of cholesterol
Utilization of cholesterol for synthesis of
other steroids
PCSK9
Inhibitor

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High Level of VLDL and LDL

Familial LDL
Lipoproteinemia, Nephrotic syndromes Chronic liver disease
Hypercholesterolemia

Hypothyroidism Cushing syndrome

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 NEPHROTIC
SYNDROME

IDOL: Inducible degrader of LDL Receptor; ACAT-2: Acyl-CoA

Cholesterol acyltransferase 2 Biochemistry and Molecular Biology 2021 30
 Familial hypolipoproteinemia

Low Level
Hypoproteinemia (malabsorption,
of VLDL severe burns, malnutrition)
and LDL Hyperthyroidism

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High Cardioprotective
• Reverse cholesterol transpor t system (Remove

Density •
cholesterol from peripheral tissue)
Increased atherosclerotic plaque stability

Lipoprotein
• Protection of LDL from oxidation
• Maintaining the integrity of vascular endothelium

(HDL)

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Atherosclerotic Plaque

33
 • Acquire excess cholesterol from
degraded VLDL and the periphery
High
Density • HDL undergoes an enzymatic reaction
via Lecithin Cholesterol Acyltransferase
Lipoprotein to become HDL cholesteryl ester, which
is selectively taken up by the liver and
(HDL) targeted for excretion via bile

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 NEPHROTIC
SYNDROME

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 Familial
ApoA1 abnormalities
Hypoalphalipoproteinemia
Low Level
of HDL-C:
Lecithin-cholesterol
Primary transferase (LCAT)
deficiency

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 Tobacco smoking

Obesity
Low Level
Poorly controlled Diabetes Mellitus
of HDL-C: Insulin resistance and metabolic syndrome

Secondary Chronic Kidney Disease

Certain drugs: Testosterone, Anabolic steroids

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High Level of HDL-C: Primary

Cholesterol ester transfer

Hyperalphalipoproteinemia
protein deficiency

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High Level of HDL-C: Secondary

Certain drugs: Estrogens,

Fibrates, Nicotinic acid,
Exercise
Statins, Phenytoin,
Rifampicin

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 Synthesized in liver

Stored in gallbladder

Secreted into small intestine

Bile acids
Primary bile acids enter the bile as
glycine or taurine conjugates (ratio
glycine to taurine 3:1)

Alkaline bile: the bile acids and their

conjugates are assumed to be in a salt
form- bile salts
Enterohepatic Circulation

Primary and secondary bile acids are absorbed in the ileum, and
98%-99% is returned to the liver via the portal circulation:
enterohepatic circulation

A small fraction of the bile salts escapes absorption and is

eliminated in the feces.

2
Obesity and
Insulin
Resistances

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LIPOPROTEIN

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FOOD
SOURCES
Food sources
Ketogenic
Diet

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 • Metabolic effects of a lowcarbohydrate (CHO)
high-fat diet af ter short-term metabolic
adaptation.
• In the first week of hypoenergetic diet, the
drastic decrease in glycogen stores (liver and
muscles) explains the quick weight loss.
Ketogenic • For example, 100 g of glycogen mobilized for
covering the daily glucose need would be
Diet associated with approximately 300 g of
endogenous water released and excreted,
yielding an immediate weight loss of half a
kilogram with a low energy density (about 100
kcal /100 g).
• E = energy

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Drug Induced
Dyslipidemia

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 Secondary Causes of Dyslipidemia

Condition Lipid Abnormaities

Chronic Kidney Disease, Nephrotic Syndromes ↑ LDL, ↑ TG

Hypothyroidism ↑ LDL, ↑ TG

Polycystic Ovary Syndrome ↑ LDL, ↑ TG

Pregnancy ↑ LDL, ↑ TG

Weight gain ↑ LDL, ↑ TG

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Condition Lipid Abnormaities

Metabolic Syndromes ↑ TG

Sedentary lifestyle ↑ TG

Diabetes Mellitus ↓ HDL, ↑ TG

Obesity ↓ HDL, ↑ TG

Liver Failure ↓ LDL, ↓ TG

Secondary Causes of Dyslipidemia

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References
• Ballantyne C. Clinical Lipidology: A Companion to Braunwald Heart Disease. 2009.
Saunders Elsevier

• Frayn KN. Metabolic Regulation: A Human Perspective.3rd edition. 2010.

Wiley Blackwell

• Yanai H, Yoshida H. Secondary dyslipidemia: its treatments and association

with atherosclerosis. Global Health & Medicine. 2021; 3(1):15-23

• Harvey RA. Lippincott Illustrated Biochemistry. 5th edition. 2011. Lippincott

William Wilkins

• Rodwell VW, Bender DA, Botham KM, Kennely PJ, Weil PA. 2015. Harperʼs
Illustrated Biochemistry. 30th Edition. McGraw Hill

• Ahmed B, Sultana R, Greene MW. Adipose tissue and insulin resistance in

obese. Biomedicine & Pharmacotherapy 137 (2021) 11315

• Davidson MH, Toth PP, Maki KC. 2007. Therapeutic Lipidology. Humana Press

• Vaziri ND. Disorders of lipid metabolism in nephrotic syndrome: mechanisms

and consequences. Kidney International (2016) 90, 41-52.

• US Department of Health and Human Services. Your Guide to Lowering

your Cholesterol with TLC.

• Schutz Y, Montani JP, Dullo AG. Low-carbohydrate ketogenic diets in

body weight control: Arecurrent plaguing issue of fad diets?. Obesity
Reviews. 2021; 22(S2):e13195

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 Ike.dhiah@staff.ubaya.ac.id

081 131 4411

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