Lipids Flashcards
How is ATP stored in the cell?
State two other labile forms of energy in the cell
State two long term energy sources
As creatine phosphate
- Redox agents (NADH, FADH2)
- Ionic transmembrane gradients
Carbohydrates and fats
Briefly outline the pathways glucose can follow in order to yield energy.
Which process do statins block?
Glucose can be metabolised anaerobically and aerobically.
Anaerobic pathways produces lactic acid
Aerobic pathway involved production of Acetyl CoA which in itself can follow three routes:
- Bind to citric acid in the Krebs cycle
- Produce fatty acids
- Synthesis cholesterol
Route three is inhibited by statins
Describe storage of glycogen in the body.
The liver absorbs sugars from hepatic portal veins and stores it as glycogen
There is some glycogen in astrocytes in brain
Consider fatty acid synthesis. What is special about it?
Which process is the reverse and where does it occur?
Define fat mobilisation
Fatty acids made in the body have an even number of carbon atoms. It is made in cytosol and REQUIRES ATP
Beta oxidation is the reverse of fatty acid synthesis. Mainly occurs in mitochondria thus PRODUCES ATP
Fat mobilisation is the process of shortening a fatty acid by 2C at a time. It produces ATP and Acetyl-CoA
Describe the fatty acids found in the body
Why must we ensure we eat essential fatty acids?
16-20 carbon long
50% unsaturated
Mammals have limited ability to synthesis C=C so obtain them from from diet (Essential fatty acids)
Which molecules are made from cholesterol? How does it behave in water?
What are cholesterol esters? Describe two key features of them
Steroid hormones, Vitamin D and bile acids. Amphipatically
Cholesterol covalently bonded to fatty acids
They are hydrophobic and are broken down by lipase
State two key features of Acetyl-CoA
It is the main energy precursor
Cannot be transported in plasma
What are ketone bodies?
They are molecules in solution made from Acetyl-CoA during fasting by liver. They last less than 5 hours. Acetone is made by decarboxylation in the reaction that makes them. Acetone is a waste product eliminated by kidney
E.g. Acetoacetic acid, beta-hydroxybutynic acid
How do unsaturated fats differ to saturated fats in the body?
Why are saturated fats most widely used in food manufacture ?
Unsaturated fats have lower melting points and increase fluidity of membranes. Most naturally occurring unsaturated acids are cis isomers.
Saturated and trans-saturated fats lack “kink” which usually interferes with stacking and solidation. Their high melting point makes them solid and unmobilisable
Saturated fats are solid at room temp and less vulnerable to rancidity
State the difference in nomenclature when using omega and alpa rules.
Omega: C1 is the carbon not in the carboxyl group
Alpha: C1 is the carbon within carboxyl group
Describe the four lipid pathways
- Gut to liver/periphery (Exogenous)
Lipids packed into chylomicrons and taken to liver.
Causes increased lipid plasma reading after meal - Liver to periphery
Peripheral lipids stored in muscle and adipose tissue
Packed into VLDL by liver - Periphery to liver (Reverse pathway)
Periphery send back lipids when liver stores get low.
This indicated by HDL detection in liver - Liver to Digestive tract (Bile production)
Cholesterol converted to bile acids which enables fat digestion by emulsification. Most bile reabsorbed by gut
Describe the role of lipoprotein lipase
It is an enzyme which breaks down triglycerides into glycerol and fatty acids.
This is important because triglycerides in VLDL and chylomicrons must be broken down in order to cross capillary membrane
Describe the role of a lipoprotein
Its soluble and carry lipids due to its amphipathic nature
Example: Apoliproteins- the protein within LP that hold lipids e.g. apoE
Describe the different density lipids
LDL (BAD!)- contents incorporated into atheroma, cholesterol storage anywhere possible. LDL eventually “left over” after periphery absorbs endogenous triglycerides from VLDL from liver
HDL (GOOD!)- increased HDL decreases CV risk. Involved in reverse transport pathways therefore appears when cholesterol is being used up
VLDL (BAD!)- significant risk of atheroma. Transports endogenous cholesterol and TG from liver to adipose and muscle.
IDL- This is what is left after triglyceride is removed from VLDL by periphery. It is intermediate step between VLDL and LDL. SIGN OF CV RISK
Hypercholesterolaemia is a subclass of hyperlipidaemia. Define it, its causes and treatment.
High fasting levels of plasma cholesterol
Increases risk of atherosclerosis
Causes- environment and genetics
Treatment- statins which block HMG-CoA Reductase
This is used as prophylaxis in men >50yo
Describe metabolic syndrome and its causes.
It is a cluster of conditions — increased blood pressure, high blood sugar, insulin resistance, central obesity, and abnormal cholesterol or triglyceride levels — that occur together, increasing risk of heart disease, stroke and diabetes.
How are short chained lipids transported in the blood?
Albumin bound
Outline the uptake of LDL
LDL express ApoB-100 which is how it is recognised by tissue bound lipoprotein lipase on liver and other cells
Uptake of cholesterol decreases cholesterol synthesis by cell by: decreased HMG-CoA reductase synthesis and decreases LDL receptor synthesis
LDL receptors are recycled by cells
How are LDL receptors regulated ?
PCSK9- binds to LDL receptors and results in degradation
This means decreased cholesterol being taken from blood and plasma LDL-C increases
Target for therapeutics: Antibody against PCSK9
Name 2 synthetic statins
Atorvastatin (Lipitor)
Fluvastatin (Lescol)
Name 4 natural statins
Lovastatin (metacor)
Compactin
Pravastatin (prevachol)
Simvastatin (zocor)
Explain the mechanism by which statins work
Competitive inhibitors of HMG CoA
Two classes (natural and synthetic)
Outline the biosynthesis of cholesterol
Predominantly happens in hepatocytes and intestines
Acetyl CoA (2c) -> HMG-CoA -> Mevalonate (6c) -> Squalene (30c) -> Cholesterol (27c)
HMG-CoA Reductase catalyses the conversion of HMG-CoA to mevalonate. This is the rate determine step and cholesterol and mevalonate act as feedback inhibitors on this enzymes. It is a target site for STATINS
HMG CoA Reductase is also regulated by insulin and glucagon
Describe the chemical nature of cholesterol, its metabolism and its state in storage
Give three used of it
Amphipathic
Synthesised from Acetyl CoA and eliminated by bile acids
Esterified to form cholesterol esters to store
Cholesterol in membranes increases their stability
Precursor to steroid hormones
Source of bile acids which are used in lipid digestion, absorption and cholesterol secretion
Outline the citrate malate cycle
CITRATE -> Acetyl CoA -> Malonyl CoA
The conversion of acetyl CoA to malonyl CoA is a carboxylation reaction and is the rate determining step, catalysed by acetyl CoA carboxylase subject to phosphorylation and under the control of glucagon ad insulin (removes P)
Acetyl Coa and malonyl CoA bind to fatty acid synthase forming C2 units in series of condensation reactions
Triglycerides can be metabolised in two pathway. Explain the synthesis of triglycerides from acetyl-CoA (for storage)
Occurs in liver and adipocytes
Long chain built from 2C derived from acetyl CoA
IN CYTOSOL (however acetyl CoA in mitochondria so exported via citrate malate cycle)
Triglycerides can be metabolised in two pathwayS. Explain the b-oxidation of triglycerides
Occurs in mitochondria (and peroxisomes) to release energy
Long fatty acids are oxidised, removing 2-carbon fragments (Acetyl-CoA) at a time. Acetyl-CoA is oxidised in citric cycle producing carbon dioxide
Fatty acids must be ACTIVATED by attachment of CoA (cytosol)
Transfer of acetyl-CoA across mitochondrial membrane is the RATE LIMITING STEP
Progressive oxidation of fatty acids (2C/time) to form Acetyl-CoA
In each cycle: 1 Acetyl-CoA, 1 FADH2, 1 NADH
Outline the digestion of triglycerides
- emulsified by bile acids
- hydrolysed by pancreatic triacylglycerol lipase
- product mixture= mixture of fatty acids and mono/diacyglycerols
- Absorbed by intestinal mucosa (bile acids essential)
State five functions of lipids
- cell membrane- phospholipid bilayer, cholesterol, glycolipids
- energy generation- TGs
- Inter and intracellular signalling events- steroid hormones
- metabolism- bile acid formation
- insulation of neurones (myelin sheath) and organ protection
How are fatty acids transported across the mitochondrial membrane?
Long fatty acids cross from cytosol to mitochondrial matrix for oxidation via carnitine shuttle
Involves carnitine palmitoyl transferase I and carnitine palmitoyl transferase II
The system is neeeded to transport long fatty acids whose transit of the inner membrane is thermodynamically unfavourable (not needed for medium and short chained fatty acids)
CoA doesn’t cross the inner membrane, thus 2 pools of CoA exist. The mitochondrial pool of CoA is primarily involved in oxidative degradation of fatty acids, pyruvate and amino acids
Cytosolic CoA pool is involved in synthesis of fatty acids
