Lipids finak Flashcards
What are Lipids?
Hydrophobic heterogeneous organic molecules
Soluble in organic solvents
What do lipids make up?
Phospholipids in membranes
Triacylglycerols in adipose droplets
Lipoproteins (often in blood)
What do lipids provide?
- Store of energy
- Membrane structural elements
- Source of Vit ADEK
- Signalling molecules
- Hormones
- CoFactors
What re the 5 mian classes of lipids?
- Fatty Acids
- Glycolipids
- Steroids
- Phospholipids
- Triacylglycerols
How do we number FA?
Number of Carbons:no.doublebonds (where the bonds are)
e.g. 18:2 (9,12)
What can we tell from a FA described as 19:3 (3,5,12)
19 carbon chain
3 C=C bonds
Double bonds at 3=4, 5=6 & 12=13.
What are hte 2 essetial FA?
Linoleic Acid & linolenic Acid
Why are they essential?
We cant introduce double C=C bonds beyond Carbon 9 so must get them from plants
What kind of fat is ‘good’?
Polyunsaturated Fats e.g. Veg Oil
What fat is ‘bad’?
Saturated Fats e.g. Beef
What fats are relaly fucking awful for ya?
Transfats e.g. hard margerine man made by hydrogenation of Veg oil.
What does linoleic acid provide?
Arachidonic acid which metabolizes to eicosanoids like leukotiren & prostoglandins
Omega-6 FA
What does Linolenic acid provide?
Omega-3 FA
What is the use of Omega-6 FA?
Lower plasma cholesterol & TAG
What are the symptoms of an essential FA deficiencY?
- ADHD
- Depression
- Chronic intersitnal disease
- Reproductive failure
- Kidney/liver disease
How are FA released from TAG?
Epinephrine activates HSL
Hormone sensitive Lipase releases FA
What inihbits HSL?
Insulin & High plasma glucose
How are FA transported in the blood?
Free FA are complexed with albumin
Most FA is esterified & carried in lipoproteins
What are the 4 types of lipoprotein in increasing density order?
- Chylomicron
- Very low density lipoprotein (VLDL)
- Low Density Lipoprotein (LDL)
- High density lipoprotein (HDL)
What is in chylomicrons & VLDL?
TAG
What is stored in LDL & HDL?
Cholesterol
Where do chylomicrons go?
Transport FA from intestines to tissues
Where does VLDL go?
Transports TAG from liver to tissue
Where does LDL go?
Takes cholesterol to extrahepatic tissues (very bad)
Where does HDL go?
Takes cholesterol from tissue to the liver for elimination (Very good)
What causes atherosclerosis?
Obesity or a genetic defect in LDL receptors can lead to excess LDL which can cause atherosclerosis
What are the products of B-oxidation?
Acetyl CoA
NADH
FADH2
Where does B-oxidation occur?
Mitochondrial Matrix
What are the 3 phases of B-oxidation??
Activation in cytosol
TRansport into matrix
Degradation
How is the FA activted in beta-oxidation?
Activated in cytosol to a fatty acyl CoA
How does the carnitine shuttle work?
Carnitine Palmitoyl-transferase (CAT) carries the Acyl group thorugh the membrane attached to carnitine then releases it on the other side where it binds to more CoA.
How is the carnitine shuttle inhibited?
CAT inhibited by Malonyl-CoA.
The main agent for FA synthesis so ensures they dont occur simultaneously
What deos a CAT-1 deficiency cause?
Little B-oxidation leading to hypoglycaemia
How do you treat a CAT-1 deficiency?
Treat immediately with IV glucose
Long term with medium chain FA that dont need a carnitine shuttle
What are the main reactions in the degradation of a FA?
Oxidation
Hydration
Oxidation
Thiolysis (Cleavage)
What is produced for every B-oxidation cycle?
- An acyl group 2 carbons shorter than before
- An Acetyl-CoA group
- 1 NADH
- 1 FADH2
How do we determine the energy output of a FA when completely broken down?
Every: - FADH2 -> 2ATP - NADH -> 3ATP - Acetyl CoA -> 12ATP Remember to remove 2 for the production of palmitoyl-CoA at the start
What happens to FA over 22 carbons inlenth?
They undergo a preliminary B-oxidation in a peroxisome which is less efficient because no FADH2 is made
What do defects in the peroxisome B-oxidation lead to?
Very Long Chain Fatty Acid (VLC-FA) accumulatin in blood/tissue
Why is no FA gluconeogenic?
Because they break down to Acetyl-CoA which cant undergo gluconeogenesis due to the pyruvate->acetyl-CoA reaction being irreversible
What happens to excess Acetyl-CoA?
Becomes Ketone Bodies in liver
What are ketones used for?
Fuels the brain, cardiac muscle & skeletal muscle
What happens if theyres excess ketone bodies?
Ketonemia
Ketonuria
Acidemia
Fruity breath from acetone
What is diabetes ketosis?
When theres a lack of insulin HSL isnt inhibited
- > increased lipolysis
- > increased blood FA
- > more B-oxidation
- > increased Acetyl-CoA
- > Ketonemia, ketonuria, acidemia
Where does FA synthesis occur?
Cytosol of:
Liver
Mammary glands
Adipose tissue
What enzyme controls FA synthesis?
Fatty Acid Synthase
What FA is produced in FA synthesis?
Palmitate (palmitic acid)
What is the overall equation for Palmitate syntehsis?
8 Acetyl-CoA + 14 NADPH + 14H+ + 7ATP
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Palmitate + 8 CoA + 14 NADP+ + 7ADP + 7Pi + 7 H2OAcetyl-CoA is made in the matrix but FA syntehsis occurs in the cytosol. How does it move out the mitochondria?
The citrate shuttle
What else is produced in the citrate shuttle?
NADPH
What is the building block of FA syntehiss?
Malonyl-CoA
Made from Acetyl-coA
What are the reactions in FA syntehsis?
Condensation
Reduction
Dehydration
Reduction
What carries the intermediates dring FA syntehsis?
ACP (Acyl carrier Protein)
What cleaves the ACP off the acyl group at the end of FA synthesis?
Thiosterase
What is TAG made of?
Triacylglycerols are esters of FAs & glycerol
What are phospholipids made of?
2 FA & a glycerol
What are bile salts derived from?
Cholesterol
What part of digestion occurs in the small intestine?
Pancreatic enzymes (lipases) break down lipids. PRomoted by emulsification by bile salts & peristalsis
How are products of lipid digestion absorbed?
Products form mixed micelles with bile salts
Then approach the bursh border membrane where theyre released from the micelle & enter the intestinal cells by diffusion
What happens if lipid malabsorption occurs?
Steatorrhea - excess fat in teh faeces causing them to float & take on a shiny appearence
How are lipids transported from the intestine?
Lipids resyntehsised into TAG, Phospholipids & cholesterol in intestinal cells.
Then packaged with apoB-48 for solubility into chylomicrons
Then exocytosed into the blood
What happens to TAG at tissue?
Its hydrolysed to FA & glycerol by lipoprotein lipase
What happens to the FA & glycerol at tissues?
Either reformed to TAg & stored as adipose droplets.
OR:
- the glycerol is converted to G-3-P then put into glycolysis/gluconeogenesis
- The FA undergoes B-oxidation for energy
