Lecture 22: Lipids and FA Metabolism Flashcards
Role of fatty acids
High energy fuel source that can be oxidized into energy. Stored as triacylglycerols (TAGs). Also building blocks for phospho/glycolipids, hydrophobic protein mods (covalent targeting for membranes), and hormone/intracellular messengers
Fatty acid nomenclature
Carboxyl carbon = C1
Then alpha, beta, gamma
Omega = last carbon in chain
FA numerical formula
C’s : # dbl bonds (dbl bond locations, C-term.) e.g. 18:2 (9,12)
Common saturated FAs
Myristic, palmitic, stearic acid (14/16/18:0)
Common unsaturated FAs
Palmitoleic, oleic, linoleic, linolenic, arachidonic acid
TAG roles
FA storage in adipocytes for other tissues and in muscle for self. TAGs sourced from G3P (glycolysis), so GLUT4 dominates in fat/muscle (insulin activated)
Hormonal regulation of TAG metabolism
Glucagon, epi -> breakdown
Insulin -> synthesis, -| breakdown
Obesity
Overly full fat stores; rupture of fat cells leads to a chronic inflammatory state. Excess lipid overflow is due to abnormal TAG accumulation and is associated with insulin resistance
Key enzyme in lipolysis (TAG breakdown)
HSL; hormone sensitive lipase
Pyrophosphatase function in FA oxidation
Activation of FA oxidation occurs with attaching FA to CoA to create acyl CoA. Pyrophosphatase on PPi pulls this activity toward products
Control of FA oxidation
Long chain FA-CoA is always synthesized in the cytosol, requiring transport by CPT shuttle into the mitochondria for oxidation. Not true for medium/short chain (synth in mitochondria)
Diabetic ketoacidosis
Very high ketone bodies from unrestrained lipolysis despite high blood glucose. Life threatening.
Regulation of CPT-1
Malonyl-CoA inhibits CPT-1; produced by ACC for FA synthesis
Regulation of Acetyl-CoA Carboxylase (ACC)
PKA and AMP-activated protein kinase (AMPK) phosphorylate and inhibit ACC; thus low energy inhibs FA synthesis and uninhibs FA oxidation
Medium Chain Acyl-CoA DH Deficiency
One of most common inherited metabolic errors; diagnosed with med. chain dicarboxylic acids, carnitine ester, glycine in urine.
Impaired beta-oxid. leads to more glucose use and inhibited gluconeogenesis -> hypoglycemia