LSM3210 YHJ L3: beta oxidation of fatty acids

where are TG / TAG / dietary fats usually stored in (which kind of cells?)

WHITE adipose tissue

what is the disease caused by loss / lowered amounts of adipose tissue ?

lipodystrophy

what are the symptoms of lipodystrophy?

fatty livers, diabetes, heart disease

why does lipodystrophy occur?

because there is lowered amount of WHITE adipose cells in our body → adipose tissue now has a more limited capacity to store fat → more fat circulate around the body and stored in other tissues (but they are not as efficient)

how are lipids transported in our blood?

via lipoproteins (eg chylomicron, VLDL, IDL, LDL, HDL)

how are our FA mobilised from TAG in the white adipose tissues?

1. ATGL (adipose triglyceride lipase

   • converts TAG —> DAG (diacylglyceride)

   • releases 1 free fatty acid

2. HSL (hormone sensitive lipase)

   • converts DAG —> MAG

   • is the rate limiting step

   • releases 1 free FA

3. MGL (monoacylglycerol lipase)

   • converts MAG —> glycerol

   • releases 1 free FA

what is the enzyme responsible for activation / priming of fatty acids before translocation?

Acyl-CoA synthetase

what is the important thing needed to transport cytosolic FA into mitochondria?

carnitine carrier protein

what is the rate limiting step in beta oxidation / translocation of FA from cytosol into mitochondria?

the conversion of acyl-CoA + carnitine → acyl-carnitine (catalysed by CPT1)

what are the 4 enzymes in beta oxidation after translocation into mitochondria?

1. AD (dehydrogenation)

   • FADH2 produced → go into the TCA cycle

2. EH (hydrogenation)

3. HAD (dehydrogenation)

   • NADH produced

   • goes into TCA cycle

4. KT (cleavage)

what are the 2 types of regulation of beta oxidation enzymes?

1. allosteric regulation

   • product inhibition

   • NAD/NADH ratio

   • acetyl coA / CoA ratio

2. transcriptional regulation

   • PPARa

   • PGC1a

   • these target the FAO genes

what are the diseases associated with beta oxidation?

1. steatosis

2. NAFLD

3. NASH

4. cirrhosis

only cirrhosis is irreversible

all these are fatty liver disease without alcohol

what are the treatments for fatty liver disease? + the consequences / effect of the drug

resmetirom → activates thyroid hormone receptor beta

consequences?

1. increase beta oxidation of FFA

2. increase mitochondria biogenesis = increase beta oxidation of FFA

3. increase expression of LDLR → increase uptake of LDL from blood into hepatocytes

fatty acid oxidation release how much energy?

1 palmitate (FA) → >100 ATP [AKA VERYVERY EXERGONIC]