SLIDE 1 Lipid Metabolism
- Glucose not the only source of energy for an organism
- _________________________________ used as an energy source
Glucose Fatty acids
- readily available energy source
- used when energy demands normal
- ____________________ of energy
- used when energy ________________
- release more energy than glucose
Lipid oxidation for energy source
b-oxidation: process of
1
SLIDE 2
Lipid Metabolism
Lipid synthesis Acetyl-CoA from TCA cycle used to _____________________________ _____________________ converted to acetyl-CoA
2
SLIDE 3
Lipid Metabolism
Cellular localization of lipid metabolism
b-oxidation - ____________ Acetyl-CoA formation - ______ Fatty acid chain elongation - ___
3
SLIDE 4 Fatty Acids
amphipathic lipid -carboxyl group polar end (hydrophilic)
- hydrocarbon chain nonpolar tail (hydrophobic)
- even # of carbon atoms
- hydrocarbon chain
unbranched
double bonds
double bonds
always cis
4
SLIDE 5
Triacylglycerols
(triglycerides)
Triacylglycerols - ester linkage of a fatty acid to each OH of glycerol polar nonpolar Generally, same F.A. esterified to all three positions on glycerol Not found in membranes but act to store F.A.’s for metabolic energy source
5
SLIDE 6
Phosphoacylglycerols
(phospholipids)
Phosphatidyl esters
6
SLIDE 7 Lipid Metabolism
Release of fatty acids from triacylglycerols and phospholipids triacylglycerols
- ______________
- breaks bonds between ____
_______________________
- most often _______________
phospholipids
- _____________________
- breaks bonds between F.A.
and OH of glycerol
- not so often _______________
7
SLIDE 8 Lipid Metabolism
Release of fatty acids from triacylglycerols
- Epinephrine hormone activates
_________________________.
- Each F.A. released from glycerol
- F.A. has _____________________
- caffeine ______________________
Why do distance athletes drink coffee before event?
- induces F.A. __________________
- saves carbohydrates for later in the
event
8
SLIDE 9 Lipid Metabolism
Activation of F.A. - bonding of F.A. carboxyl group ____________________
- general term of ______________________
- exact name depends ______________________
- ___________________________________
- energy, by hydrolysis of two phosphate bonds
- takes place in cytoplasm
Oxidation of F.A.
9
SLIDE 10 Lipid Metabolism
b-oxidation
- acyl-CoA moved from cytoplasm to ____________________________
- ___________ units removed from F.A. in
4 rxn cycle
- carbons removed from _________
___________________
- b carbon becomes carboxyl
carbon
_____________ in successive 2 carbon acetyl-CoA removals
into ________________
10
SLIDE 11 Lipid Metabolism
b-oxidation Step 1: oxidation of Ca - Cb bond to ____________________
- acyl-CoA __________________
- FAD reduced to FADH2
- double bond in __________
configuration
- product: trans-D2-Enoyl-CoA
11
SLIDE 12 Lipid Metabolism
b-oxidation Step 2: Ca - Cb double bond hydrated _______________________
- enoyl-CoA __________________
- uses H2O
- product: b-hydroxyacyl-CoA
12
SLIDE 13 Lipid Metabolism
b-oxidation Step 3: Cb _______________________
- hydroxyacyl-CoA ______________
- reduces NAD+ to NADH
- product: b-ketoacyl-CoA
- set up for Cb to become
__________________
13
SLIDE 14 Lipid Metabolism
b-oxidation Step 4: Ca - Cb___________________
- ___________________
- requires CoA, added to remaining
F.A.
undergoes a new round of b-oxidation
- product: acetyl-CoA
- Cb becomes
- Ca goes with acetyl-CoA
- acetyl-CoA enters ________
14
SLIDE 15 Lipid Metabolism
b-oxidation
- b-oxidation of even # F.A. gives __________________________
- C-18 stearic acid = ____________________________
- requires ____________________ of b-oxidation
15
SLIDE 16
Lipid Metabolism
b-oxidation energy production
__________ __________ __________ __________ __________ __________ __________ __________
16
SLIDE 17
Lipid Metabolism
b-oxidation energy production 3 Glucose = 18 carbons = __________ 1 stearic acid = 18 carbons = ________ Why the difference in ATP production? A more ______________ can donate more e- for ATP production
17
SLIDE 18 Lipid Metabolism
b-oxidation H2O production Metabolic H2O - _____________________________ aerobic metabolism Large amount of water from b-oxidation can be used ___________________ _____________________________________ Camels - hump contains stored lipids Kangaroo rats
- diet of seeds high in lipids
- live indefinitely with out
external H2O
18
SLIDE 19
Lipid Metabolism
Fatty Acid Biosynthesis Acetyl-CoA is transported to the ___________________ Once in cytoplasm, converted _____________
19
SLIDE 20 Lipid Metabolism
Fatty Acid Biosynthesis 2 Priming events:
- 1. Acetate transferred to ___________________________________
- 2. Acetate transferred to b-ketoacyl-S-ACP-synthase (_____________)
- acetyl-KSase combined
with ____________, forming acetoacetyl-ACP malonyl - carboxylated acetate
20
SLIDE 21 Lipid Metabolism
Fatty Acid Biosynthesis
- next three steps are exact ___________________
- reduces ketone from acetate
- ____________________
- dehydration to double bond
- reduction to __________________
- produces butyrl-ACP
- process requires ______________
- uses 2 NADH
21
SLIDE 22 Lipid Metabolism
Fatty Acid Biosynthesis
- butyrl-ACP added _________________ malonyl-ACP
- same 3 reactions take place to
_______________________ 16:0 palmitate
required length achieved
22
SLIDE 23 Lipid Metabolism
Fatty Acid Biosynthesis F.A. synthesis takes ___________________ Fatty acid synthase - large protein complex containing all the _______________ _________________ As with glycolysis and gluconeogenesis b-oxidation and F.A. synthesis are ____ _______________________________ But, are opposites in terms of end products
- double bonds introduced by enzymes
in the _________________________
23
SLIDE 24
Lipid Metabolism
Triacylglycerol Biosynthesis Generally, free F.A. _____________________ F.A. added to OH groups of ___________
24
SLIDE 25 Lipid Metabolism
Phospholipid Biosynthesis
- 2 F.A. added to ____________________
- polar head group ___________________________
FA1 FA2
25
SLIDE 26 Lipid Metabolism
Cholesterol Biosynthesis
- essential part of __________________
- used to make __________________
- major contributor ___________________
- synthesized through ______________________________
Isoprenoid pathway - use of ___________ to produce _______ compounds Isoprene Isoprene units can be condensed to form intermediates with carbons ____________________________
26
SLIDE 27 Lipid Metabolism
Cholesterol Biosynthesis Isoprenoid pathway involved in synthesis of:
Chlorophyll a
- ________________ (coenzyme Q, e- transport)
ubiquinone
Vitamin A
27
SLIDE 28 Lipid Metabolism
Cholesterol Biosynthesis Plants make many isoprenoids, > 20,000
capsidiol
carotenoids
b-carotene in tomatoes
b-carotene used by mammals to make vitamin A, ______________________
Vitamin A
28
SLIDE 29 Lipid Metabolism
Cholesterol Biosynthesis Isoprenoid pathway general scheme:
acetate
(acetyl-CoA)
____
S-CoA O
acetyl-CoA mevalonate ____ x 3
HO OH O OH
mevalonate Isopentenyl diphosphate isopentenyl diphosphate (_____) ____
OPP
OPP
geranyl diphosphate (_____) geranyl diphosphate ____
OPP
farnesyl diphosphate (_____) ____ farnesyl diphosphate ____ ….C50 ____ Intermediates can be used for ______________ ____________________________________. ____
29
SLIDE 30 Lipid Metabolism
Cholesterol Biosynthesis
C2
S-CoA O
acetyl-CoA C6 x 3
HO OH O OH
mevalonate Isopentenyl diphosphate C5
OPP
C10
OPP
geranyl diphosphate
OPP
C15 farnesyl diphosphate x 2
HO
___________ _____ ___________ _____
30
SLIDE 31 Lipid Metabolism
Cholesterol Biosynthesis C30 Squalene is cyclized to _____________ 19 reactions by 19 enzymes convert C30 lanosterol to C27 cholesterol 3 carbons lost _____________
- _______________________
- f liver cells.
31
SLIDE 32 Lipid Metabolism
Cholesterol Metabolism Steroid hormone production
- cholesterol converted to _____________
- pregnenolone to __________________
- sex hormones
_______________ _______________
cortisone
carbohydrate, protein, F.A. metabolism
aldosterone _______________________
32
SLIDE 33 Lipid Metabolism
Cholesterol Metabolism Atherosclerosis - condition of blocked artery by __________________ ____________________ Cholesterol is transported in the blood in the form of __________________________
- cholesterol
- phospholipids
- proteins
LDL - ____________________ lipoprotein HDL - ____________________ lipoprotein Density determined by amount of protein
33
SLIDE 34 Lipid Metabolism
Cholesterol Metabolism
- LDL internalized to a cell by binding
__________________________
___________________________
- cholesterol used in membranes
- oversupply of cholesterol turns off
________________________. What type of regulation is this?
- also stops production _____________
- LDL can not be internalized, builds
up in arteries, clogged arteries
34
SLIDE 35 Lipid Metabolism
Cholesterol Metabolism Familial hypercholesterolemia - genetic defect in genes that produce _____________________________________
- LDL never internalized to cell
- extremely high _________________________
- almost always lethal
- die before 20 years old
- reported heat attacks in 2 year olds
35
SLIDE 36 Lipid Metabolism
Cholesterol Metabolism
Joe Goldstein (1940 - ) Michael Brown (1941 - ) University of Texas Southwestern Medical Center at Dallas
- 1985 , Nobel Prize in Physiology or Medicine
- for their discoveries concerning the regulation of cholesterol metabolism
36
SLIDE 37 Lipid Metabolism
Cholesterol Metabolism HDL - “good cholesterol”
- transports cholesterol from blood ___________________________
Ideal blood levels
[LDL] [HDL]
- HDL can be increased by _______________________________
- HDL is reduce by _______________________________
37