LIPID METABOLISM

Nguyễn Thị Hoàng Yến

1. Absorption fatty acids
2. Fatty acid synthesis
3. Fatty acid oxidation
(Beta oxidation)
4. Ketone bodies
5. Cholesterol metabolism
ABSORPTION
FATTY ACIDS
LIPOPROTEINS
FATTY ACID
SYNTHESIS
FATTY ACID SYNTHESIS
Citrate

ATP citrate
lyase

Acetyl CoA + Oxaloacetate

Acetyl CoA
carboxylase *
Malonyl CoA
ACETYL CoA CARBOXYLASE
Fatty acid
synthase
 FATTY ACID SYNTHESIS

Acetyl CoA + CO2 + ATP Malonyl CoA + ADP + Pi

 FA SYNTHESIS - DOUBLE BOND
Fatty acyl CoA desaturase -> adding cis double bonds -> in the SER
Requirement:
1. 02
2. NADH
3. cytochrome b5
4. (FAD)-linked reductase
The first = bond -> carbons 9 and 10,
Ex: oleic acid, 18:1(9), palmitoleic acid, 16:1(9).
FATTY ACID
OXIDATION
 FATTY ACID OXIDATION

1
In Adipose
tissue Liver
ATGL: Adipose TriGlyceride Lipase
HSL: Hormone Sensitive Lipase (HSL)
MGL: Mono Acyl Glycerol lipase
 FATTY ACID OXIDATION

Acyl CoA synthase

2 Fatty Acid + CoA + 2ATP Fatty Acyl CoA + 2AMP + 2PPi
 FATTY ACID OXIDATION
ONLY in mitochondria matrix
Ex: Muscle

CARNITINE SHUTTLE
rate-limiting transport process
CPT1: carnitine palmitoyltransferase I
CPT2: carnitine palmitoyltransferase II
 BETA OXIDATION

*
FATTY ACID OXIDATION
BETA OXIDATION

Short chain FA?

Very long chain FA (C > 22)?
Odd-chain fatty acids?
Unsaturated fatty acids?

How many ATP for a single

molecule of palmitate
(C=16) ?
FATTY ACID OXIDATION
ODD-CHAIN FATTY ACIDS

(TCA)
FATTY ACID OXIDATION
UNSATURATED FATTY ACIDS
FATTY ACID OXIDATION UNSATURATED FATTY ACIDS
FATTY ACID OXIDATION
UNSATURATED FATTY ACIDS

- Isomerases
- Dehydrogenase
- Reductases
 FATTY ACID OXIDATION
CARNITINE DEFICIENCY
Primary carnitine def. Secondary carnitine def.

- Causes: autosomal recessive inheritance - Causes: decrease carnitine

Decrease uptake carnitine to cells Ex: liver disease, valproic acid, deficiencies
Ex: muscle, kidneys in CPT-I and CPT-II
- Consequences: - Consequences: Slow growth, low muscle
Cardiomyopathy tone, motor delays, and delayed
Skeletal muscle myopathy intellectual development and seizures
Encephalopathy - Treatment:
Impaired liver function • avoid fasting
- Treatment: carnitine supplementation • adopting a diet high in carbohydrates and
low in fat
• medium-chain TAG supplementation
MEDIUM-CHAIN FATTY ACYL CoA DEHYDROGENASE (MCAD) DEFICIENCY

- autosomal recessive disorder

- Incidence: 1:14000,
Caucasian (North Europe)
- Symptoms:
• C6–C10 fatty acids + their
ester accumulate -> urine
• Hypoglycemia
• Hypoketonemia
- Treatment: avoid fasting
FATTY ACID OXIDATION
ZELLWEGER SYNDROME

- Cause: inherited in an autosomal recessive disorder,

gene (PEX5) -> impaired peroxisome biogenesis
(proteins)
- Consequences: accumulation of VLCFAs (in the liver,
kidneys, and nervous tissue)
- Symptoms:
• hepatomegaly
• severe neurologic defects
• skeletal mal-formations
• high levels of copper and iron in the blood
- Treatment: no
 FATTY ACID OXIDATION
X-LINKED ADRENOLEUKODYSTROPHY
KETONES
BODIES
 KETOGENESIS

- During a fasting/ special diet

- In mitochondria in the liver
- HMG CoA: 3-Hydroxy-3-methylglutaryl CoA
- HMG CoA synthase -> rate-limiting step
KETOLYSLS

Thiophorase
 DIABETIC KETOACIDOSIS
Normal conc.: 3 mg/dL
Uncontrolled T1D: 90 mg/dL, urinary excretion 5000 mg/24 h

pKa ~ 4 pKa ~ 4

Clinical symptoms:
Acetone -> fruit odor on the breath
nausea, vomiting, dehydration, electrolyte imbalance
Accelerated heartbeat (tachycardia)
Rapid breathing or long, deep breathing (Kussmaul breathing)
Loss of consciousness, coma and death
CHOLESTEROL
METABOLISM
 CHOLESTEROL METABOLISM

- ACAT2: Acetyl Coenzyme A

Acetyltransferase 2 (thiolase)

* - HMGCS: HMG CoA synthase

- HMGCR: HMG CoA reductase

(rate-limiting step) *

- FDFT1: Farnesyl-diphosphate
farnesyltransferase 1

- SQLE: squalene epoxidase

- SOAT: sterol O-acyltransferase

HORMONAL REGULATION OF CHOLESTEROL SYNTHESIS
 BILE SATLS amphipathic character
Bile acids:
- cholic acid - Glycine
+ - Taurine
- chenodeoxycholic acid
CHOLESTEROL GALLSTONE DISEASE
cholesterol-based gallstones -> Cholelithiasis