Oxidation Of Fatty Acids and Ketone bodies Flashcards
Where are fatty acids mainly oxidized
Where are they stored
Why are they oxidized
- heart , liver or kidney
- stored in adipose tissue
-done during fasting state to produce energy
-during stressful moments ( fight or
Flight )
Types of pancreas cells and what they do
-found in islets of langerhans ( cluster of endocrine cells )
1 alpha - secrete glucagon when glucose is gone
2 beta - secrete insulin when glucose is high
How is flight or fight response glucose made
-sympathetic nervous system stimulated adrenal medulla cells ( chromafin ) to secrete 80% epinephrine and 20% norepinephrine
What structures surround TRIG’s in adipose cells
-perilipin bound to CGI
-ester cleaving enzymes
1 adipose triglyceride lipase
2 hormone sensitive lipase
3 monoglyceride lipase
Describe process from activation of perilipin to cleaving to 1st hormone
- the 3 hormones bind to GPCR on adipocytes, cAMP activates protein kinase A which phosphorylates perilipin bound to CGI
- CGI dissociates and activates adipose triglyceride lipase
- ATL cleaved 1st ester bond and 1st FFA released and we are left with diacylglyceride
Describe how middle ester bond is cleaved
And the 3rd
-PKA phosphorylates hormone sensitive lipase wc cleaved 2nd ester bond freeing FFA and monoglyceride
/PKA phosphorylates monoglyceride lipase cleaved 3rd ester bond and releases FFA and glycerol
Fate of glycerol and FFA
How are they transported in blood and why
-pushed into blood stream to be taken to other cells for oxidation into ATP
- glycerol diffuses into blood
- FFA transported by albumin as it aint water soluble
1st step of beta oxidation and why and enzyme involved
Problem of this step ( CoA added )
-to prevent fatty acid from leaving cell
-fatty acyl CoA synthetase converts fatty acid into fatty acid acetyl CoA
( ATP dependent )
-fatty acetyl CoA can’t move into mitochondria
Describe transport stage of fatty acids into mitochondria and mediators
- transporter protein ( carnitine acetyl transferase type 1 ) on outer mito membrane removes CoA and adds carnitine
- product is now fatty acetyl carnitine and can move into Mito via a translocase
Problem of adding carnitine once in mito and solution
- can move out of mito translocase
- remove carnitine and add acetyl CoA back. Enzyme is carnitine Acetyl CoA transferase type 2
What happens to carnitine after being removed
-pushed out of Mito into cytosol ti CAT 1 for recycling
Describe 1st step of beta oxidation and mediators
- fatty acetyl CoA is oxidized by acetyl CoA dehydrogenase
- FAD reduced to FADH2
- double bond formed between alpha and beta carbon atoms
Describe 2nd step of beta oxidation and mediators
- H20 added across trans double bond ( trans delta 2 Enol CoA ) and alpha and beta by enzyme Enol CoA transferase
- product beta hydroxyl acetyl CoA
Describe 3rd step of beta oxidation and mediators
-beta hydroxyl acetyl CoA has its 2 hydrides removed at beta and a double bond between C and Oxygen forming beta ketoacyl CoA
/enzyme is beta ketoacyl dehydrogenase
Describe what happens at 4th step of beta oxidation and mediators
- beta ketoacyl CoA cleaved at Alpha and beta bond to form acetyl CoA ( krebbs cycle ) and a fatty acyl CoA recycled at 1st step of beta oxidation but 2 carbons short
- enzyme is thiolase
How to calculate number of acetyl CoA’s and rounds of oxidation of a even number fatty acid
- divide by 2 for number of acetyl CoA made
- less one of acetyl CoA for Cycles of beta oxidation
What are the 2 products of beta oxidation of odd chain fatty acids and fates of the products
- acetyl CoA ( krebbs cycle )
- propionly CoA ( 3 carbon molecule ) converted to succinyl CoA
1st step in converting propionly CoA into succinly CoA and mediators
And 2nd step
- C atom form HCO3 or CO2 added to propionly CoA
- Enzyme is propionly CoA carboxylase ( biotin dependent )
-methyl malonyl CoA mutase enzyme ( B12 ) dependent converts methyl Malonyl CoA into succinly CoA
What does deficiency of B12 cause
List the fates of succinly CoA
- perinicious anemia
- fatigue
- converted into succinate ( krebb cycle intermediate )
- converted into OAA then Malate ( gluconeogenesis )
- converted into poryphyrin and heme group used to make erythrocytes
Describe oxidation of fats inside peroxisomes
- has transporters to take in fatty acetyl CoA which is oxidized by FAD
- but FADH2 hydrides taken and given to o2 and H2O to form peroxide which has numerous cellular functions
How does the body prevent excess peroxide’s
-catalyse enzyme breaks down peroxide into water and oxygen
Describe oxidation of odd chain fatty acids
- eg polmitoleate activated and moved into Mito matrix
- goes 3 cycles of beta oxidation , 3 acetyl CoA released until It is now delta 3 Enol CoA
- enzyme cis delta 3 Enol CoA isomerase converts delta 3 Enol CoA into trans delta 2 Enol CoA
- beta oxidation continues
Why can’t step 1 enzyme of beta oxidation act on cis delta 3 Enol CoA
-it adds a double bond to alpha and beta carbons but in this case double bond already present between beta and 4th carbon
Describe oxidation of even numbered unsaturated fatty acid
( linoleate example ) 18:2 delta 9,12
-activate and translocated into Mito matrix
/undergoes 3 cycles of beta oxidation and reduced to 12 carbon fatty acid ( cis delta 3 Enol CoA )
/enzyme cis delta 3 Enol CoA isomerase converts it into trans delta 2 Enol CoA which undergoes beta oxidation
/now we form cis delta 4 Enol CoA
-undergoes 1st step by acetyl CoA dehydrogenase forming 2,4 dienol CoA intermediate wc isn’t compatible with hydratase
-2,4 dienol CoA reductase removes double bonds and adds one at carbon 3 and 4
-isomerase shifts it to alpha and beta carbons
-beta oxidation continues
When are ketone bodies utilized as an energy source
1 hypoglycemia
2 prolonged starvation
3 low carbohydrate diet
4 diabetes mellitus
Where are ketone bodies made and where are they mainly utilized
- made in the liver ( main site of fat oxidation )
- heart , brain and muscle
What happens when there is low glucose in the body ( to OAA , glucose and acetyl CoA )
- increased beta oxidation of fats
- increased ATP , acetyl CoA and NADH
- oxaloacetate converted into glucose via gluconeogenesis and less OAA means acetyl CoA can’t fuse with it to form citrate
- acetyl CoA now In excess and undergoes ketogenesis
Describe 1st step of ketogenesis and mediators
- 2 acetyl CoA’s fuse and there is loss of a CoA
- we form aceto acetyl CoA
- Enzyme is acetyl CoA acyl transferase
Describe 2nd step of ketogenesis
And it’s defining reaction characteristics
- aceto acetyl CoA has another acetyl CoA added and a CoA is removed
- we form HMG CoA ( 3 hydroxy 3 methy glyceterol CoA )
- Enzyme is HMG CoA synthetase
-rate determining step
What happens to HMG CoA after formed and mediators
-HMG CoA lyase enzyme removes a acetyl CoA to form acetoacetate ( 1st ketone body )
2 reactions that can occur to acetoacetate
1 NADH drops hydrides on it to form beta hydroxybutyrate ( 2nd ketone body )
-enzyme is beta hydroxybutyrate dehydrogenase
2 decarboxylated by CO2 removal and enzyme acetoacetate decarboxylase ( removes a C atom ) to form acetone
What occurs to the breath of diabetic people and describe how it come about
-diabetic mellitus patience undergo numerous ketone metabolism , produce a lot of acetone which the body tries to exhale giving breath a fruity smell
What is ketonemia and ketonuria
What is the normal ketone bodies conc
Which 2 ketone bodies are used as energy sources
- excess of ketone bodies in blood
- in urine
- 0.2 mmol/ L
- acetoacetate and beta hydroxybutyrate
We do ketone bodies do at the brain stem
/they stimulate the brain stem at the area of postremia ( chemotrigger zone )which triggers vomiting
-excessive and loss salts and fluids
-low blood pressure due to hypovolemia ( liquid portion of plasma is low )
Comatose state
Dangers of ketone bodies in the blood
-they are acidic , ( donate protons in plasma ) making it acidic , or ketoacidosis
- Bohr effect
- chromatin clumping
Describe how the body fights against
1 bicarbonate carbonic acid buffer tries but only for a few seconds
2 hyperventilate to reduce CO2 and reduce carbonic acid formation ( kossmal breathing - rapid deep inspirations )
Describe how ketone bodies are utilized as energy source
1 beta hydroxybutyrate dehydrogenase collects hydrides from beta hydroxybutyrate and converts it into acetoacetate ( other acetoacetate from blood )
2 enzyme thiophorase transfers CoA from succinly CoA and transfers to acetoacetate and forms aceto acetyl CoA
3 enzyme acetyl CoA acyl transferase adds another CoA and cleaves aceto acetyl CoA into 2 acetyl CoA. Which are used in krebbs cycle
What doesn’t the brain use FA direct
/can’t diffuse Through the blood brain barrier
