01:694:301 Lecture Notes - Lecture 22: Carnitine O-Palmitoyltransferase, Adenylyl Cyclase, Acetyl-Coa
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14 Nov 2018
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Chapter 22 – ‘Fatty Acid Metabolism’
• Look carefully at Figure 22.2 (640) and outline handout
o The similarity of fatty acid beta oxidation (in red, left) to the way succinate is
handled in CAC (509,442) makes this pathways an easy one to learn
• Fatty acids are stored as triglycerides, and hydrolyzed by lipase enzymes
o Triglycerides are uncharged esters of fatty acids with glycerol;
! Highly concentrated stores of metabolic energy because
reduced
and
anhydrous
• Stores more energy than glycogen and glucose
! Found predominately in cytoplasm of adipose cells; also in muscle, thru body
o Fatty acids mobilizes from triglycerides are oxidized to meet cell’s energy needs
o Lipases are under the control of PKA (protein kinase A) and hormones, etc
! Lipases are secreted by pancreas and degrade triglycerides to free fatty acids
! Glucagon and epinephrine trigger 7TM receptors " activates adenylate
cyclase " cAMP " PKA which phosphorylates
perilipin
and lipase
• To access lipid energy reserves, three stages of processing must occur:
o 1) Lipids are mobilized; triglycerides are degraded to fatty acids and glycerol
o 2) After reaching tissues in need, fatty acids must be activated and transported to mito
for degradation
o 3) Fatty acids are broken down " acetyl CoA " CAC
• FFA are inophores which could uncouple mitochondria, so they are rapidly attached to
Coenzyme A by acyl CoA synthetase (or fatty acid thiokinase) via acyl-AMP
o Prior to entering the mito matrix, FFA are ‘activated’ through formation of thioester
linkage to CoA;
! ATP drives formation of thioester bond; (and irreversible hydrolysis of pyrophosphate)
! Catalyzed by
fatty acid thiokinase
(
acyl CoA synthethase
)
! Note that acyl adenylate often formed when activating carboxyl groups in biosynthesis
• Cyto acyl CoA cannot enter the mito w/o help of carnitine acyltransferase (Fig 22.8)
o Special shuttle system is needed to carry activated FA across mito membrane
o After crossing membrane, acyl group is transferred back to CoA by same
enzyme (reverse of the rxn below)
• The steps of beta oxidation are shown (Fig. 22.9) and the enzymes (Table 22.1)