Lipid Metabolism Flashcards
Where does lipid metabolism occur and what are the sources for it?
Liver, Dietary Carbs
End Product of FA synthesis?How many Carbons?
Palmitic Acid, 16
3 steps in FA synthesis?
Cytosolic entry of Acetyl Coa, generation of Malonyl Coa, Fatty acid chain formation
What is phase 1 of FA synthesis and what happens?
know enzymes!!
- Acetyl CoA is condensed with OAA to form citrate (citrate synthase)
- Citrate transported from mito to cytosol, uses transporter
- citrate converted back to OAA and acetyl Coa
(citrate lyase)
-Acetyl CoA used for FA synthesis in cytoplasm - OAA reduced to malate (malate dehydrogenase)
- malate transported to mito via malate a ketoglutarate transporter
made into OAA(malate dehydrogenase)
6.cytosolic malate made into pyruvate (malic enzyme)
-this pyruvate does to mitochondria, made into OAA by (pyruvate carboxylase)
What is phase 2 of FA synthesis, what happens? know enzymes!
-MALONYL COA IS MADE!!
-Acetlyl coa made into malonyl coa via carboxylation
ACC
(USES ATP + BIOTIN)
What is the rate limiting step of FA SYNTHESIS + ENZYME?
Acetly Coa to MAlonyl Coa, (ACC)!
What is MALONYL COA? Why is it important?
- Substrate for FA Synthesis
- Inhibits carnitine acyl transferase
- Prevents FA synthesis + degradation from happening at the same time
What is phase 3 of FA Synthesis? Know enzymes, plus what promotes and stopes it
- 2 Carbons from Malonyl coA added to growing palmitate chaine (Fatty Acid Synthase Complex)
- uses Acetyl Coa +NADPH
- Insulin +glucocorticoid hormones promote
- PUFA stops
What is Fatty Acid Synthase?
- 2 Dimers, multi enzymes
- 7 enzyme activities, acyl carrier protein
How many acetyl CoA and malonyl Coa are used to make palmitate,how many CoA are made?
1, 7, 8 coa made
what kind of reactions are made by FAS?
seven cycles total, then product released Condensation Reduction Dehydration Reduction
What are the sources of NADPH ?
Malic enzyme: 1 molecule of NADPH
malate to pyruvate
PPP:2-12 nadph
rxn of Fatty acid synthesis
- condensation: acetyl + malonyl= acetoacetyl
- reduction: acetoacetyl+ NADPH=D-3-hydroxybutyl
- dehydration: D-3hydroxybutyl- H2O= Crotonyl
- reduction: crotonyl+ NADPH= Butyryl
Regulators steps of FA syn
Phase 1: Atp citrate lyase
- Acetyl COA carboxylase
- FAS
How is Acetyl Coa carboxylase regulated?
- Inactive as dimer, active as polymer
- citrate +, palmitate -
- Dephosphorylation (+): Insulin
- Phosphorylation (-): epi, glucagon, AMP
-gene expression up by high carb, low fat diet
Hos is FAS regulated?
-Phos sugars: increase effect
At gene level:
- Insulin +glucocorticoid hormones: +
- high carb/low fat diet +
- high fat, starvation, - syn
- high PUFA: -
Where is palmitate elongated into longer chain?
SER or mitochondria, 2 C at a time
What is is used as a carbon donor for elongation?
What is used as a reducing agent
SER: malonyl COA
Mito:Acetyl Coa
NADPH is a reducer
What is desaturation? How is it done? Were is it done?
- Introduction of double bonds in FA
- 0ccur in SER, use NADPH (Acyl CoA Desaturases)
What kind of FA can’t be synthesized by humans?
FA with double bond beyond carbon 9 and 10 cannot be synthesized in humans
What are Essential Fatty Acids
Need to ingest them or their precursors in diet
Essential Fatty Acids ? which are they? what do they make?
–Linoleic acid (ω6) :arachidonic acid
–Linolenic acid ( ω3) : EPA, DHA
What kind of lipids are FA put into?
TAGS
How much KCAL does do TAGS store in muscle and fat?
100,000 kCa
What are TAGs?
major storage form of Fatty Acids
Where do we get TAGS?
- Diet in intestine
- De novo in liver
- De novo in fat cells
How are TAGs made in intestine? What is it promoted by?
- Dietary TAGs to Monoacylglycerol (MAG) and FFA in intestinal lumen
- intestinal cells resynthesize TAGs using MAG as backbone and adding 2 FFAs
- TAGs packaged with apolipoproteins to form a lipoprotein called chylomicron
- Chylomicrons are released into the lymphatic system and enter blood via thoracic duct
-TAG synthesis in intestinal cells promoted by dietary TAGs!!
Steps of Tag synthesis in liver?
Glycerol-3-phosphate to LysophosphatidicAcid to PhosphatidicAcid to Diacylglycerol to Triacylglycerol
How is TAG made in liver? How is it promoted?
- Glucose and Glycerol formGlycerol-3-phosphate (G-3-P)
- G-3-P used as backbone for TAG synthesis
- FFA ( come from Acetyl Coa) added to G-3-P to form TAGs
- TAGs form VLDL and released
- TAG synthesis promoted by excess carbs
How is TAGs made in fat cells? How is it promoted?
- Glucose forms G-3-P, used as backbone
- FFA come from breakdown of chylomicrons and VLDL in blood
- TAGs stored in Adipocytes
- TAG synthesis in adipocytes promoted by excess carbohydrates and fats
Which lipases break down TAGS?
–Hormone sensitive lipase (HSL)
–Lipoprotein lipase (LPL)
–Monoacylglycerol lipase (MAG Lipase)
What does HSL do? How does it work?
-Makes TAG a DAG, hunger and exercise activate it
-Glucagon, Epi, Norepi +, phosphorylate
GPCR, Perilipin and HS Lipase important
-Insulin -, dephosphorylates HSL via PP1
What are Perilipin? what do they do?
- Family of proteins that coat lipid droplets in adipocytes and muscle cells
- Regulate lipolysis by controlling physical access to HSL
- Overexpression of Perilipin 1 inhibits lipolysis and its knock-out has converse effect
Fatty Acid Oxidation entails 2 phases
1: Fatty Acid Activation, Happens in cytosol
2. B oxidation, in matrix
How is FA transported during phase 1, what are the steps?
Carnitine shuttle
- Fattly Acyl CoA synthetase
- outer mito membrane
- Uses ATP to activate LCFAs
- FA + CoA to make FACoA - CPT1
- Intermembrane space
- makes FA Carnitine
-Ratelimiting step, malonyl Coa-
- CACT
- FA Carnitine into intermembrane space - CPT2
- Located in the inner mt-membrane
- Forms FA-CoA
- FA CoA in matrix
What happens during Phase 2 of FA oxidation? What does it generate?
- 4 steps
- Makes Acetly Coa, FADH2, NADH
What are the four steps of FA Oxidation?
- Acyl CoA dehydrogenase (ACAD) : oxidizes the βcarbon to produce FADH2 and trans-enoyl-CoA!!
- Enoyl CoA hydratase saturates the alkene with water to form βhydroxy acyl CoA!!
- β hydroxy acyl CoA dehydrogenase oxidizes the carbon to form ketoacyl CoA!! and NADH
- Acyl CoA acyl transferase makes fatly acyl CoA
What is the end product of FA breakdown
FA broken down to acetyl CoA
B oxidation of odd numbered FAs, how does it happen?
- Metabolized until Propionyl-CoA remains (3 carbons)
- p ropionyl CoA Carboxylase uses ATP to make Methylmalonyl-CoA
- Methylmalonyl CoA Mutase generates Succinyl-CoA
- 4.Succinyl-CoA enters TCA cycl
How are unsaturated FAs oxidized?
- Metabolized until unsaturation is reached
- Reductasereduces double bond
- Isomerasemoves the disruptive bond
How are VLCFAS oxidized?
- in peroxisomes, do not make ATP
- First step is catalyzed by acyl-CoA oxidase
- Peroxisomal carnitine acyltransferase used for transport
What is TFP and what is its relevance?
has activities of enoyl CoA hydratase, hydroxy acylCoA dehydrogenase and ketothiolase
involved with defects in FA oxidation
MCAD Deficiency, what is it? what happens?
impairs breakdown of MCFAs
secondary carnitine deficiency
C8 FA accumulates in liver, poisonous, interferes with urea cycle, elevated levels of ammonia
depend on glucose
Treatment mainly preventative
What are ketone bodies? what causes them to be made
Fasting/Starvation = Excessive b-oxidation of FAs , ↑[Acetyl-CoA]
Water-Soluble and Acidic Compounds:
- Acetoacetate2.b-Hydroxybutyrate3. Acetone
- Produced in Liver Only:
- Provide energy for peripheral tissues and during fasting & brain!!!! during starvation
What are the steps to making ketones?
Acetoacetyl coa to hmg coa to acetoacetate to acetone or b-Hydroxybutyrate
primary sources of energy?
First few hours of fasting?
After 1 day of fasting
After 3 days of fasting
After 1 – 2 weeks of starvation
After 2 – 3 months of starvation
energy source is blood glucose, followed by glycogen, gluconeogenesis
energy source is TAGs stored in adipose tissue
ketone bodies made in liver and proteins in muscles are broken down
brain switches to ketone bodies
TAGs depleted, proteins main source
What is Pathological ketoacidosis?
glucagon/insulin ratio is increased, favoring FA breakdown.
Increased gluconeogenesis - reduced oxaloacetate
Acetone exhaled via breath, fruity odor in individuals with uncontrolled diabetes.
