Term
What are the 2 broad classes of fatty acids and what are their purpose? |
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Definition
1. Energy production FAs - TAGS, triglycerides, etc., main purpose is to provide energy
2. Membranes - Lipids made for structural integrity in membranes, include cholesterol |
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Term
What are the 2 advantages of storing energy in the form of fatty acids? |
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Definition
1. Fatty acids contain about twice as much energy per gram as other sources
2. Fat is water insoluble so its storage does not require water, whereas other forms do |
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Term
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Definition
A nonpolar, hydrophobic molecule |
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Term
Describe the nomenclature of the 3 important carbons on a fatty acid, and from which side oxidation occurs |
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Definition
1. alpha and beta - from the carboxyl end
2. omega - methyl carbon at non polar end
3. Oxidation (beta oxidation) starts from the carboxyl end and moves toward the omega carbon |
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Term
Which fatty acids are produced biologically, cis or trans? |
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Definition
cis
(puts a kink in the chain allowing increased fluidity) |
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Term
What types of fatty acids are classified as essential? |
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Definition
Fatty acids with double bonds close to the omega carbon (we cannot synthesize these)
(ex. EPA and DHA - which are good for nutritive supplement, brain health, and membrane use) |
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Term
What compound serves as the precursor molecule for ketone bodies and fatty acids? |
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Definition
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Term
Where does fatty acid synthesis take place? |
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Definition
Entirely in the cytoplasm |
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Term
How is acetyl CoA transported out of the mitochondrion to the cytoplasm for fatty acid synthesis? |
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Definition
1. Acetyl CoA combines with oxaloacetate to make citrate 2. Citrate is transported out 3. Citrate lyase cleaves citrate into Acetyl CoA and oxaloacetate 4. Oxaloacetate is transported back in as malate or pyruvate, and Acetyl CoA is now in the cytoplasm |
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Term
Describe the overall (general steps) synthesis of fatty acids from Acetyl CoA |
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Definition
1. Acetyl CoA combines with bicarbonate (via acetyl CoA carboxylase) to make malonyl CoA (committed, rate limiting, regulated step) 2. Condensation 3. Reduction (via NADPH) 4. Dehydration 5. Reduction (via NADPH)
Notes: Each step increases the length by 2 carbon units, and the end product is ALWAYS Pamitic acid (16:0 fatty acid) |
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Term
What are the two parts of fatty acid synthase enzyme? |
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Definition
1. Cysteine residue 2. Acyl carrier protein |
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Term
Describe the step by step synthesis of fatty acids from acetyl CoA |
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Definition
Note: ACP = acyl carrier protein, CYS = cysteine residue
1. Acetyl CoA binds to ACP 2. Acetyl CoA switches to CYS 3. Malonyl CoA binds to ACP and binds Acetyl CoA (complex attached to ACP) 4. 3 keto group becomes an alcohol 5. alcohol goes through dehydration (making double bond at carbon 2) 6. Double bond gets reduced 7. 4 Carbon fatty acid switches from ACP to CYC and process continues (its a cycle) |
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Term
How is the 16 carbon fatty acid cleaved from fatty acid synthase? In what circumstances is it not a 16 carbon fatty acid? |
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Definition
1. Thioesterase cleaves palmitic acid (16 carbon FA) from fatty acid synthase
2. In breast milk it cleaves at 8-12 carbons (these are more easily digestible in the infant GI tract) |
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Term
Describe the local regulation of Acetyl-CoA carboxylase |
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Definition
1. Increased citrate levels increases activity
2. Increased long chain fatty acyl CoA decreases its activity |
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Term
Describe the global regulation of fatty acid synthesis |
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Definition
1. Insulin (GLOBAL STORE ENERGY HORMONE) promotes fatty acid synthesis by dephosphorylating (and therefore activating) Acetyl CoA carboxylase, it also induces Fatty Acid Synthase expression
2. Glucagon and Epinephrine (GLOBAL STOP STORING ENERGY HORMONES) phosphorylates Acetyl CoA carboxylase (inactivating it) and suppresses fatty acid synthase. this is done via a cAMP activated protein kinase |
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Term
What two modifying processes happen to Palmitic Acid to make other non essential fatty acids? |
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Definition
1. Elongation 2. Desaturation |
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Term
What are the two location elongation can take place? What are the two carbon sources for elongation? How does elongation differ in the brain then other tissues? |
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Definition
1. Can happen in ER or Mitochondrion
2. ER uses malonyl CoA as carbon source, mitochondrion uses Acetyl CoA
3. Most tissues elongate to stearate (18:0), but brain elongates to longer FAs |
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Term
How far from the 1 carbon can we make double bonds? |
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Definition
Anywhere up to the 9th carbon. Any farther away from the 1 carbon (or closer to the omega carbon) cannot be done by our enzymes and must be obtained in the diet |
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Term
How are fatty acids stored? |
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Definition
Triacylglycerols.
3 fatty acids are joined to glycerol for storage in tissue (main long term energy storage system in humans) |
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Term
What is the mechanism for adding fatty acids to glycerol? |
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Definition
1. Glycerol (easily obtained from fructose) is converted to glycerol phosphate 2. Acyltransferases add two fatty acids (one at a time) to glycerol phosphate where the hydroxyl groups are 3. Phosphatase removes the phosphate group and replaces it with a hydroxyl group 4. Acyltransferases add the third fatty acid making triacylglycerol |
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Term
Describe how fatty acids are broken down for energy |
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Definition
1. Global stop storing hormones (glucagon, epinephrine) activate cAMP 2. cAMP activates protein kinase A 3. PKA phosphorylates and activates hormone sensitive lipase, which cleaves the FAs off of triacylglycerol 4. FAs are bound to albumin for transport to muscle and liver, glycerol can be used for gluconeogenesis |
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Term
Describe how FAs get inside mitonchondrion for energy use |
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Definition
1. Fatty acids become Fatty acyl-CoA 2. CPT I transfers the acyl to carnitine making acylcarnitine (across outer membrane) 3. Translocase moves acylcarinitine into the inner membrane 4. CPT II removes Acyl CoA from carnitine and recycles the carnitine back out. Acyl CoA can undergo beta-oxidation
Note: Malonyl CoA, a precursor for FA synthesis, inhibits CPT I (makes sense, malonyl CoA's presence is indicative of FA synthesis, not degradation and use) |
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Term
how does beta oxidation work? |
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Definition
Almost identical (not completely identical) to the reverse of FA synthesis. Steps are 1: oxidation 2: hydration 3: oxidation 4: cleavage
2 carbon units are sequentially removed from the carboxyl end of the acid |
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Term
How many ATPs does beta oxidation of one palmitic acid yield? |
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Definition
96 ATP
7 Acetyl CoA's are removed each removal yields and NADH and an FADH2 |
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Term
What is Adrenoleukodystrophy (X-ALD) |
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Definition
Long chain fatty acids (VLCFA's) cannot be broken down in the peroxisome, leads to demyelination of CNS.
Treament is oleic acid, which inhibits fatty acid synthase, and erucic acid, which is an inhibitor of the elongation system in the brain. These two stop VLCFA synthesis |
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Term
What are the 2 ketone bodies used for energy sources? Where are they synthesized? Where are they utilized for energy? |
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Definition
1. Acetoacetic acid and beta-hydroxybutyric acid are the two ketone bodies
2. They are synthesized in the mitochondria of the liver
3. They are made purely for export, the liver cannot use these |
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Term
When are ketone bodies used as an energy source? |
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Definition
Ketone bodies are primarily used for an energy source during a fast when glucose is not readily available or an inefficiency such as insulin deficiency exists |
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Term
What is the reason for producing ketone bodies? |
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Definition
The brain cannot use FAs for energy and relies on glucose
When glucose becomes low in supply, it switches to ketone bodies for energy which helps ensure glucose supplies are not totally depleted by other tissues such as muscles |
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