25 Lipid Metabolism Lipogenesis

Normal range free fatty acid

0.2-0.6 mmo/L

Normal range Triglycerides

0.9-2.0 mmol/L

Normal range phospholipid

1.8-5.8mmol/L

normal range cholesterol

3.8-6.7 mmol/L

definition lipogeesis

synthesis of fatty acid from acetyl coA during fed state

site lipogenesis

cytosol of cell of liver kidney brain lung mammary gland and adipose tissue

material required for lipogenesis

acetyl coa, NADPH, ATP, Mn2+, biotin and HCO3 as a source of CO2

end product lipogenesis

palmitate

steps involved in lipogenesis

1. formation of malonyl coa

   acetyl coa carboxylase convert acetyl coa to malonyl coa in the presence of ATP, biotin and bicarbonate

2. formation of fatty acid from malonyl coa

   guna fatty acid synthase

sources of NADPH

dari HMP Pathway sama dari reaction yang convert malate to pyruvate guna malic enzyme

source of acetyl coa

Pyruvate undergoes oxidative decarboxylation to form Acetyl CoA within the mitochondria.

extra note:

Pyruvate is converted to acetyl CoA in mitochondria.

• Acetyl CoA combines with oxaloacetate to form citrate.

• Citrate moves to cytoplasm and is cleaved to acetyl CoA and oxaloacetate by ATP citrate lyase.

• Acetyl CoA is used for malonyl CoA synthesis to form palmitate.

regulation of fatty acid synthesis or the other name for this is Lipogenesis

• Regulation of Lipogenesis:

  • Nutritional Factor: Lipogenesis ↑ in high carb, ↓ in caloric restriction & high fat diet.

  • Molecular Factors: Short & long term mechanisms regulate lipogenesis.

    • Short-term factors: Insulin, glucose, and dietary intake.

    • Long-term factors: Hormones like leptin, adiponectin, and gene expression changes.

    • Short-term: Insulin promotes lipogenesis by activating enzymes in the process.

    • Long-term: Hormones like leptin and adiponectin influence gene expression to regulate lipogenesis over extended periods.

what is this meas? Molecular Factors: Short term mechanisms regulate lipogenesis.

Short term control:

• Allosteric control:

  • Acetyl CoA carboxylase activated by citrate

  • Inhibited by long chain acyl CoA

  • Competition between long chain fatty acids and citrate

  • Inhibition of mitochondrial tricarboxylate transporter

• Covalent modification:

  • Dephosphorylated form of Acetyl CoA carboxylase is active

  • Epinephrine and glucagon phosphorylate the enzyme. so ini deactivated the enzyme.

  • Insulin activates phosphatase to convert the enzyme to active form

what is this meas? Molecular Factors: Long term mechanisms regulate lipogenesis.

Long term control:

• Adaptive control:

  • High carb, low fat diet post-fasting increases enzyme levels

• Hormonal factors:

  • Insulin: Stimulates lipogenesis by increasing glucose transport and pyruvate availability

  • Glucagon & Epinephrine: Inhibit acetyl CoA carboxylase via cAMP

  • Catecholamines: Inhibit acetyl CoA carboxylase through adrenergic receptors and Ca2+/calmodulin dependent protein kinase