Mod 8 Bmsc 230 Flashcards
B-Oxidation
Repetitive process by which fatty acids are broken into acetyl coa in the matrix
- acetyl coa produced will enter citric acid cycle
- involves release of NADH and FADH2 (donate electrons to etc - atp generation)
- B-oxidation cuz B carbon (third from the carboxyl end) gets oxidized every round
Double bonds/ kinks in hydrocarbon chains ___ the melting point of the fatty acid
Lower
The last carbon at the methyl carbon end, when numbering from the methyl carbon end
Omega (w)
If the double bond is three carbons away from the methyl end, it’s called an omega 3 fatty acid
Fatty acid storage
Stored as triacylglycerol, a neutral lipid, in adipose tissue
Adipokines
Small biomolecules secreted by adipose tissue that control overall body metabolism and appetite
Triacylglycerol structure
Three fatty acids attached to a glycerol backbone via ester bonds
Lipase cleaves the fatty acids off the glycerol and releases them into the blood to be used by other organs —> linked to CoA once in the cell —> undergo beta oxidation in the matrix to release acetyl coA
First stage of fatty acid degradation
Mobilization of fatty acids from triacylglycerol in adipose tissue (hydrolysis rxn that uses three water molecules to cleave off three fatty acid residues)
Three lipases and their mechanism
Adipose triglyceride lipase (ATGL - triacylglycerol) and Hormone-sensitive lipase (HS-lipase - diacylglycerol)
- activated by epinephrine and glucagon that signal need for more fuel (bind to receptor on adipose cell and activate camp —> camp activates protein kinase a which activates ATGL and HS lipase)
Fatty acid and glycerol transportation
- Fatty acids bound to the blood protein albumin - go to tissues that need fuel
- glycerol goes to liver and gets converted to dihydroxyacetone phosphate (can undergo glycolysis or gluconeogenesis) - usually gluconeogenesis
Carnitine
Brings fatty acids into mitochondria so they can be oxidized
Second stage of fatty acid degradation
Activation of fatty acids and transport to mitochondria
- fatty acids brought into cell through diffusion through special proteins
- fatty acids activated by reacting with Coenzyme A to form acyl CoA on the outer mitochondrial membrane (rxn consumes 1 atp and breaks it down into amp and ppi, broken down into two Pi; so 2 high energy bonds are broken for every CoA attached to a fatty acid)
- acyl of Acyl CoA transferred to biomolecule called carnitine —> formation of acyl carnitine by enzyme carnitine acyltransferase 1 (on cytoplasmic side of the inner mitochondrial membrane)
- acyl carnitine goes across into mitochondria through a translocase —> carnitine acyltransferase II reverses rxn (reformation of acyl CoA + free carnitine shuttled into cytosol so it can be re-esterified to another fatty acid to bring it into the mitochondria)
Third stage of fatty acid degradation
Degradation of fatty Acyl CoA to Acetyl CoA:
- acyl CoA now in mitochondrial matrix - will undergo beta oxidation
4 reactions in every round of beta oxidation
Acyl CoA —> Trans-/_\2- Enoyl CoA —> 3-Hydroxyacyl CoA —> 3-Ketoacyl CoA —> Acyl CoA + Acetyl CoA
- Oxidation step producing FADH2: Acyl CoA dehydrogenase (trans double bond produced between a and b carbons due to oxidation)
- Hydration step: enoyl CoA hydratase (OH on b and H on a carbon - product is 3-hydroxyacyl CoA)
- Oxidation step producing NADH: B-hydroxyacyl CoA dehydrogenase (oxidized to 3-ketoacyl CoA - B Carbon now fully oxidized (C=O))
- Thiolysis step: Thiolase (CoA used to cleave off an acetyl CoA unit and leave behind an acyl CoA two carbons shorter - SH attacks bond between a and b) - final round of B oxidation releases two acetyl CoA
Palmitate
16-carbon fatty acid yielding 106 ATP upon oxidation
- requires 7 rounds of B oxidation
- technically, 108, but two high energy bonds needed to activate the fatty acid to get it into the mitochondria so -2 = 106 vs 30 from glucose
(Don’t confuse with palmitoleate - unsaturated, double bond at carbon 9)
Regulation of fatty acid degradation
Synthesis and degradation DONT happen at the same time (reciprocal regulation)
- epinephrine and glucagon activate triacylglycerol breakdown in adipose but also inhibit the fatty acid synthesis enzyme, acetyl CoA carboxylase
- carboxylation of acetyl CoA to malonyl CoA necessary for fatty acid synthesis- malonyl CoA inhibits carnitine transferase 1 and therefore b oxidation
Unsaturated fatty acids
Double bonds
Three stages of fatty acid degradation
- Mobilization of fatty acids from triacylglycerol in adipose tissue
- Activation of fatty acids and transport to mitochondria
- Degradation of fatty Acyl CoA to Acetyl CoA
Palmitoleate degradation
16 carbon fatty acid with a double bond between carbon 9 and 10
- palmitoleoyl-CoA —> 3 cycles of B oxidation and becomes cis-/\ 3-enoyl CoA (isn’t a substrate for acyl CoA dehydrogenase) —> CIS-/\3-ENOYL COA ISOMERASE (Converts cis double bond between c3 and c4 to trans double bond between c2 and c3) converts to Trans-/_\2- Enoyl CoA- b oxidation can continue
Linoleoyl CoA
Fatty acid with twO double bonds requiring a reductase
- 2,4-dienoyl CoA not a substrate for beta oxidation —> reductase reduces the double bond between carbons 4 and 5 using NADPH —> trans-/\3-enoyl CoA converted to trans-/\2-enoyl CoA by cis/_\3 Enoyl CoA isomerase
Oxidation of odd chain fatty acids
In the last round of beta oxidation, one acetyl CoA and a 3-carbon acyl CoA called propionyl CoA is produced (rather than two acetyl CoA’s)
- Propionyl CoA gets carboxylated at carbon 3 using atp —> D-methylmalonyl CoA (4c molecule) —> L-methylmalonyl CoA (catalyzed by methylmalonyl CoA mutase, a vitamin B12 containing enzyme) —> Succinyl CoA (can enter CA cycle)
Ketone bodies
synthesized from acetyl CoA in the liver (instead of going into the citric acid cycle) - water soluble fuel crossing the blood brain barrier (brain- but can be used by kidney and heart). Ketone body production increases when fatty acid oxidation is high:
- starvation
- uncontrolled diabetes
Three different ketone bodies produced from acetyl CoA in the matrix
Acetoacetate, B-hydroxybutarate, acetone
2 acetyl CoA make Acetoacetate —> converted to 3-hydroxybutarate or acetone through SPONTANEOUS decarboxylation (reduce and get rid of co through NADH to make 3hydroxybutarate) — Acetoacetyl CoA was an intermediate
Degaradation of ketone bodies
3-hydroxybutarate and acetoacetate can be metabolized back to acetyl CoA to be used in the CA cycle - acetone exhaled
- Liver cannot convert acetoacetate to acetoacetyl CoA so it doesn’t use up the acetoacetate itself (fatty acids are liver’s source of energy)
High levels of acetoacetate act on adipose tissue and ____ lipolysis
Inhibit
- by indicating an abundance of acetyl CoA
Ketone body degradation process
- dehydrogenase converts 3-hydroxybutarate to acetoacetate
- CoA transferase coverts acetoacetate to acetoacetyl CoA (succinyl CoA added, succinate leaves)
- thiolase converts acetoacetyl CoA to 2 acetyl CoA molecules (CoA added)
Diabetes
- Insufficient amounts of or response to insulin
- lack of oxaloacetate
- high b Oxidation of fatty acids so a large amount of acetyl CoA
- acetyl coa can’t enter citric acid cycle cuz of lack of oxaloacetate so it’s converted to ketone bodies —> ketoacidosis (ketone bodies are acidic)
Insulin
- Increases glucose uptake by the liver
- metabolism of glucose through glycolysis to pyruvate (some pyruvate converted to oxaloacetate)
Fatty acid degradation is aerobic/anaerobic
Aerobic
