Cell Metabolism 2 Flashcards
5 main classes of lipids
Free fatty acids, steroids, triacylglycerides, phospholipids, glycolipids
Why are fatty acids a useful storage molecule
It is reduces and anhydrous
What are the three main sources from which fat is derived from
Diet, lipogenesis ( from scratch) and storage depots in adipose tissue
Where are bike salts made and stored
Made in liver and stored in gall bladder
Where are bile salts generated from
Cholesterol. During digestion they move from bile duct into small intestine
What do bile salts do
Emulsify fats in the intestine, aiding the digestion and absorption of fat soluble vitamins A, D,E and K
What does a lack of bile salts result in
Lack of bile salts results in the majority of fats passing through the gut undigested and unabsorbed resulting in fatty stool ( steatorrhea)
What is orlistat( aka tetrahydrolipstatin)
Potent inhibitor of gastric and pancreatic lipases. It therefore reduces fat absorption and can be used to treat obesity
What are the main side effects of orlistat
Abdominal pain, increased flats, steatorrhea and urgency to defecate
What is the role of chylomicrons
Dietary fat transport
What is the role of very low density lipoproteins
Endogenous fat transport
What is the role of immediate density lipoproteins
LDL precursor
What is the function of low density lipoproteins
Cholesterol transport
What is the role of high density lipoproteins
Reverse cholesterol transport
What happens before the triglycerides are incorporated into chylomicrons
Digested dietary products are absorbed by the enterocytes that line the brush border of the small intestine. Triglycerides are resynthesized under the control of several enzymes prior to the incorporation into chylomicrons
What happens to the chylomicrons
They are transported via the lymphatic system and into the blood stream. They acquire apoproteins from HDL following release into blood stream. Lipoprotein lipase is located one the capillary endothelial cells lining tissues including adipose, heart and skeletal muscle. Fatty acid undergoes beta oxidation. Glycerol is returned to liver for use in gluconeogenesis
What is the anatomy of lipoproteins
Phospholipid monolayer containing cholesterol and apoproteins. This surrounds a core of cholesterol esters and triacylglycerols
How are cholesterol esters synthesised
In the plasma from cholesterol and the acyl chain of phosphatidylcholine ( lecithin) via a reaction catalysed by lecithin cholesterol actltransferase( LCAT)
What is the role of HDL
Good cholesterol as it takes cholesterol from the peripheral tissues back to the liver for use or disposal ( reverse cholesterol transport). They help to lower total serum cholesterol
What is the role of LDL
LDL’s is bad cholesterol as the elevation of LDL
levels lead to atherosclerosis( hardening of arteries)
Where does beta oxidation occur and what is the end product produced
Beta oxidation occurs in the mitochondria and ultimately results in the production of acetyl CoA
Describe the beta oxidation of fatty acids
Fatty aids are converted into an acetyl CoA species. During this process ATP-> AMP so 2 HIGH ENERGY BONDS ARE USED. This occurs on the outer mitochondrial membrane. To transport the species into the matrix, it is coupled to the molecule carnitine to form acyl carnitine; moved to and from matrix by translocase (shuttle mechanism ).
What happens during primary carnitine deficiency
Mutations in genes encoding carnitine transporter results in a reduced ability of cells to take up carnitine needed for beta oxidation of fatty vides. If there isn’t enough fatty acids inside mitochondrial you will feel tired. Carnitor is used as a supplement / treatment
Describe the process of the beta oxidation cycle
The acyl CoA undergoes a series of oxidation, hydration, oxidation and thiolysis reactions which are collectively known as beta oxidation. This results in the production of one molecule of acetyl CoA and 1 acyl CoA species which is 2 C shorter than the original. On the final cycle ( 4 acyl CoA intermediate, two acetyl CoA molecules are formed ).
What is continuously removed from the beta oxidation cycle
2 carbons from the acyl CoA to produce acetyl CoA
Overall reaction of beta oxidation of palmitic acid
Palmitoyl CoA + 7 FAD + 7 NAD+ + 7 H20 + 7 CoA -> 8 acetyl CoA + 7FADH2 + 7 NADH
During each cycle, one molecule of FADH2 and NADH are produced.
What is ketone body formation
For acetyl coA to enter the Krebs Cycle, carbohydrate metabolism needs to have occurred as oxaloacetate is needed. But when fasting, glucose and therefore oxaloacetate production is low and acetyl coA cannot enter TCA cycle and so forms ketone bodies instead. Ketone bodies include acetoacetate, D-3-hydroxybutyrate and acetone
Do you get more ATP when you oxidise fatty acids as opposed to glucose
Yes
What occurs during fatty acid biosynthesis/ lipogensis
Fatty acids are formed sequentially by decarboxylative condensation involving acetyl CoA and malonyl CoA. Following each round of elongation, the fatty acid undergoes reduction and dehydration by sequential action of ketoreductase, dehydrated and Enol reductase.
What are the 2 enzymes involved fatty acid synthesis
Acetyl CoA carboxylase and fatty acid synthase
Difference in carriers in fatty acid synthesis and degredation
Synthesis; ACP
Degredation : CoA
Reducing power in fatty acid synthesis and degredation
Synthesis : NADPH
Degredation : FAD/NAD+
Locations of fatty acid synthesis and degredation
Synthesis : cytoplasm
Degredation ; mitochondrial matrix
Overall reaction of fatty acid synthesis
Acetyl CoA + 7 Malonyl CoA (C3) + 14 NADPH + 14 H+-> palmitate (16C) + 7 CO2 +6H2O +8COA-SH +14NaDP+
What enzyme carries out the desaturation of fatty acids
Fatty acyl-CoA desaturases
Where does de novo FA biosynthesis occur in adults
Liver, adipose tissue and lactating breast
Can we selectively target FA synthetase (FASN) in cancer?
Inhibition if FASN by celurelin ( an antifungal antibiotic) is shown to reduce tumour growth of ovarian cancer cells
Short chain acyl-CoA-dehydrogenase
<6C
Medium chain acyl CoA enzyme A dehydrogenase
6-12 C
Long chain 3-hydroxacyl CoA enzyme A dehydrogenase
C13-C21
Very Long chain acyl CoA enzyme A dehydrogenase
> 22
Medium chain acyl coenzyme A dehydrogenase deficiency
Autosomal recessive and if diagnosed patients should not go more than 10-12 hrs no food as they are not very good at breaking down fatty acids to release energy. Patients with more illness resulting in loss of appetite or severe vomiting may bee IV glucose to make sure that the body is not dependent on fatty acids for energy
What are the cotransporters in maltate aspartate shuttle and glycerol-phosphate shuttle
Maltate aspartate : NADH
Glycerol phosphate shuttle:NADH in cytoplasm and FADH in mitochondria
