01:694:301 Lecture Notes - Lecture 22: Carnitine O-Palmitoyltransferase, Adenylyl Cyclase, Acetyl-Coa

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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)
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