Lipid Formation and metabolism Flashcards
describe the structure of lipids (2)
- fatty acid ( R-COOH)
- triglycerides ( glycerol + 3 fatty acids)
what is fatty acid oxidation ?
outline in detail
(10)
B acid oxidation:
1) fatty acids enter blood stream after being separated from glycerol via Lipase
2)enter target cells via transporter protein
(Turns into ACYl COA in mitochondrial matrix via carnitine shuttle - outlined from step 3 to 6)
3)Fatty acid is ACTIVATED to the ACYCL COA
4) Acyl coA enters outer mitochondrial membrane and then the CPT1 enzyme turns it into ACYL-CARNITINE and release COA back into cytoplasm
5)Acyl Carnitine enters Mitochondria Matrix via CAT enzyme (look in ur notes for more detail)
6) CPT2 enzyme attaches COA to ACYL CARNITINE TO MAKE ACYL COA and carnitine goes back into the inter membrane space
7)OXIDATIVE CATABOLISM occurs where the fatty acyl COA is turned into :
-ACYL COA (which can combine with oxaloacetate and enter KREBS )
-2 carbon shorter fatty acycl COA
-reduced FADH2 AND NADH .
what’s fatty acid synthesis ? (6)
outline and describe …
The creation of fatty acids from acetyl-CoA and NADPH through the action of fatty acid synthases
1-Acetyl-CoA groups (from glycolysis) are transported from the mitochondria to the cytoplasm through the citrate shuttle.
2-In mitochondria, acetyl-CoA combines with oxaloacetate to form citrate.
3-Citrate is then shuttled to the cytoplasm (instead of continuing in the citric acid cycle).
4-In the cytoplasm, ATP citrate lyase hydrolyzes citrate back into acetyl-CoA and oxaloacetate.
5-Acetyl CoA carboxylase activates acetyl-CoA and converts it into malonyl-CoA.
6-Acetyl-CoA carboxylase requires biotin, ATP, and CO2.
Fatty acid synthase uses the carbons from acetyl-CoA to synthesize a new fatty acid (i.e., palmitate)- it can be extended by 2 carbons .
how are lipids transported by Lipoproteins and how is this regulated? 3
- there are chylomicrons ,VLDL , LDL and HDL and they are composed of different types of proteins and fats hence have different functions. (tend to have a hydrophobic core and a phospholipid or apolipoprotein membrane)
ie: HDL picks up excess cholesterol
what is reverse cholesterol transport ? (5)
- enzyme involned
- receptor involved
HDL picks up the cholesterol deposited by LDL in arteries .
1) HDL is secreted by the liver , combined with phospholipid to form NASCENT HDL ( a bigger HDL), which accepts the free cholesterol
2) free cholesterol is esterified to cholesterol esters via an enzyme called LCAT
3) the esters move into the core of the lipoprotein making an even bigger HDL called HDL3
4) HDL 3 grows and becomes HDL2 ( Biggest )
5) this HDL2 binds to the Liver cell via a scavenger receptor and is uptakes by liver hepatocyte .
describe the endogenous pathway of lipid metabolism
1)VLDL secreted from liver
2)APO-CII interacts with lipoprotein lipase
3)hydrolyse triglyceride to 3 fatty acids
4) go to cells for storage , hence smaller remnants are left !
5)50% is cleared by liver
50% is hydrolysed to form LDL
describe the exogenous pathway of lipid metabolism
7
1) enzymes in stomach break down food to free cholesterol, fatty acids and glycerol
2) BILE , fats are put into micelles
3) ENTEROCYTES - esterfy into cholesteryl esters and try glycerides and then packages to CHYLOMICRONS
4) Enters Lymph system , thoracic duct and then circulation .
5) Aquires APO C-II ( required to activate lipase )
6) lipase breaks down triglycerides and then stores them in fat cells
7) chylomicron decreases in size = chylomicron remnant = goes to the liver!
What happens to LDLs after endogenous pathway ?
4
1) has membrane protein called B100 ( this is how body can recognise it )
2) they float in the blood and then fit into the liver LOCK AND KEY receptor
3) receptor internalises and brings receptor and LDL into cell cytoplasm
4) PCSK9 protein tells cell not to recycle the receptor and LDL (mainly cholesterol ) is used for different purposes around the cell .
what is MCADD -Medium change Acycl Coa dehydrogenase deficiency?
what process does it affect?
how is it treated?
(5)
This effects the B oxidation of the fatty acid , the dehydrogenase enzyme removes the hydrogen atoms and makes the fatty acids smaller )
-if it is not there then B oxidation of fatty acids can’t occur
-ACADM gene mutation =rare autosomal recessive Problems can arise when:
1-people fast or vomitt= they can’t keep down their food
2-body doesn’t have any carbs for energy and the B oxidation back up won’t work!
3-this causes weakness, coma, death !!!
Treatment is :
-avoid fasting
-emergency regimen include :
energy drinks , deliver nutrition straight into the veins bypassing the gut !)
what is diabetic ketoacidosis?
(10)
what are the 2 pathways ?
treatment ?
1-effects type 1 diabetics ( when u run out of insulin , beta cells not producing enough insulin)
2-Insulin levels are very LOW this causes :
PATHWAY 1
- more gluconeogenisis (more production of glucose )
-more glycogenolysis (break down of glycogen to glucose)
-Decreased glycolysis ( converts glucose to pyruvate for respiration )
MORE GLUCOSE IN BLOOD
This leads to :
=>Hyperglycemia (glucose peed out =glucosuria)
=>glucosemia (loss of water = always need the toilet)
=>dehydration which leads to HYPOtension / shock = releases enzymes like cortisol etc which all decrease cellular glucose uptake and increase FFA
PATHWAY 2= increases LIPOLYSIS
- adipose tissue broken down =increases Fatty acids in blood, and increased lipolysis
- fats->liver->ketogenesis ->ketone bodies(we need energy because glucose is not present or working ) = acidic =acidosis
- ketonaemia ( more ketones in blood)
- ketonuria (ketones in urine )
- hyperketoneagmia ( ph in blood and urine decreases)
Treatments :
- check airways , breathing and circulation
- IV access= blood for investigation
- administration of insulin slowly ( take up glucose in blood)
- EUC-blood counts
- Urine analysis to check for glucose , ketones ,etc
what's homocystinuria ? classical homocystinuria deficiency (CBS) (5) -recessive? -metabolism of? -patients divided into ?
problem with methionine metabolism
-autosomal recessive
effects eyes, bones, cardiovascular system
-homocysteine–>cysteine normally via a CBS enzyme
-B12 and B6 needed for it to work
-IN Homocystinura = no CBS enzyme = less cysteine and more homocysteine is converted into something else
-patients are divided into Pyridoxine B6 responsive and non responsive to manage their treatments .
what’s family Hypercholesterolaemia ? what does it effect? treatment?
(5)
-FH = autosomal dominant , causes an increase in LDL in arteries causing blockage of arteries
-there is mutation in the gene which can cause:
-faulty LDL receptor so LDL isn’t taken into liver cell
-Faulty apo B100 which means the receptor won’t recognise it !
-fault is PCSK9 which means that less LDL is taken into the cell =MORE LDL IN BLOOD /Arteries
(you can spot things like a white ring around the eye. achillies tends englargement )
- causes risk of premature cardiovascular disease
-atheroscerosis ( build up of fat in artery walls)
treatment : statins , lifestyle changes (no smoking , healthy diet )
