Lipids and Metabolism Flashcards
What is the energy content per gram of carbohydrates, lipids and proteins?
Proteins: 4kcal/g
Lipids: 9kcal/g
Carbohydrates: 4kcal/g
How is energy released from organic molecules?
Oxidation reactions (loss of electrons)
(For organic molecules, the more carbon/hydrogen and less oxygen they contain, the more scope there is for oxidising them)
Why do lipids contain more energy?
They are oxygen poor and hydrogen and carbon rich
What constitutes an ‘unsaturated’ fatty acid?
What is the significance of this?
Contains at least 1 double bond, meaning they contain less hydrogens. There is no rotation around the double bond, meaning they have fixed configuration at each double bond.
Double bond provides rigidity to the fatty acid- e.g. provides more rigidity to a cell membrane.
What is meant by ‘trans’ and ‘cis’ configurations?
Trans configurations: carbon chain crosses the double bond
Cis configurations: carbon chain kinks back on itself
What does the ‘omega’ nomenclature describe?
The position of the final double bond, counting from the hydrocarbon end.
How are short chain fatty acids absorbed?
Simple diffusion across brush border of cell membrane and diffusion across basolateral membrane into blood.
How are long chain fatty acids absorbed?
Fats (triglycerides) emulsified by bile salts and phospholipids into emulsion droplets.
Digested by pancreatic lipase to monoglycerides and fatty acids.
Held in micelles, combined with bile salts and phospholipids.
Micelles diffuse into an ‘unstirred layer’ next to the surface of epithelial cells.
Monoglycerides and fatty acids diffuse into cell membrane.
Inside the cell monoglycerides and fatty acids are reassembled into triglycerides and packaged into chylomicrons
Exported across the basolateral membrane and leave the intestinal villus via the lacteals of its lymph system and into the systemic circulation.
Describe the structure of a lipoprotein
Lipids with a hydrophobic core containing triglycerides and cholesterol esters and a hydrophilic surface containing phopsholipids, free cholesterol and proteins.
What releases fatty acids from chylomicrons and VLDLs into the tissues?
Lipoprotein lipase
What are the main functions of chylomicrons?
Describe their composition
Deliver dietary (exogenous) triacylglycerols (TAG) to peripheral tissues.
High triacylglycerol, low cholesterol
What are the main functions of VLDLs?
Describe their composition
Deliver endogenous triacylglycerols to peripheral tissues.
High triacylglycerols, low cholesterol (less TAG and more cholesterol however than chylomicrons)
What is the main function of LDLs?
Describe their composition
Deliver cholesterol to peripheral tissues and liver
Low triacylglycerols, highest cholesterol (compared to chylomicrons, LDLs and HDLs)
What is the function of HDLs?
Describe their composition
Deliver cholesterol from peripheral tissues to the liver for elimination.
Lowest tryacylglycerol content (compared with chylomicrons, LDLs and VLDLs) and high cholesterol
Describe the exogenous lipid cycle
Dietary lipids absorbed in the GI tract and packaged into chylomicrons which enter the systemic circulation.
Broken down by lipoprotein lipase in the systemic circulation to remove lipid content.
Remnants of chylomicrons reach the liver via the systemic circulation.
Liver breaks down remnants of chylomicrons into cholesterol which is re-introduced to the GI tract via the biliary system.
Describe the endogenous lipid cycle
Lipids and lipoproteins occurs largely in the liver
VLDLs released from liver into systemic circulation and broken down by lipoprotein lipase into IDLs→LDLs.
LDLs are transported back to the liver and also to extrahepatic tissues, where the majority of the triacylglycerols and triglycerides removed.
HDLs then transport cholesterol back to the liver.
How is cholesterol synthesised?
de novo from acetyl-CoA in the liver (80%), intestine (10%) and skin (5%).
What is the role of cholesterol?
Essential structural component of all cell membranes.
Precursor of steroid hormones (oestrogen, aldosterone, corticosterone, cortisol), bile acids and Vitamin D.
Describe the composition of most cholesterol
Esterified form, with a fatty acid attached at carbon 3
Describe the role of the liver in cholesterol homeostasis
De novo synthesis of cholesterol
HMG-CoA reductase regulation
LDL-receptor regulation
Conversion to bile acids/salts
Secretion of free cholesterol in bile
Secretion of HDLs and VLDLs
Describe the process of cholesterol synthesis in hepatocytes
Acetyl-CoA → Acetoactyl-CoA → HMG-CoA
HMG-CoA broken down by HMG-CoA reductase into Mevalonate (irreversible, the rate-limiting step (slowest))
Mevalonate is transported into the hepatocyte to be converted into cholesterol:
- Mevalonate → C5 → C10 → C15 → C30 → Cholesterol
How do Statins work to reduce cholesterol?
Competitively inhibit HMG-CoA reductase enzyme, therefore slowing down the synthesis of endogenous cholesterol.
A compensatory up-regulation of LDL receptors occurs in an attempt to capture more circulating LDL particles, resulting in decreased plasma LDL
Also lower hepatic VLDL production and increased HDL is sometimes observed
What other beneficial cardiovascular effects do statins have?
What are the side effects and contraindications?
Other beneficial cardiovascular outcomes e.g. lowering plasma fibrinogen and enhancing fibrinolysis and anti-inflammatory effects
Adverse effects:
- GI (e.g. vomiting and diarrhoea)
- CNS (dizziness and blurred vision)
- Muscle (myositis, myalgia, myopathy)
Contraindications:
- Active liver disease
- Pregnancy
- Breast feeding
Name a clinical example where statins would be indicated
Describe this condition
Familial hypercholesterolaemia
- Inherited disease (autosomal recessive) involving a mutation in the gene coding for LDL receptors
- This leads to excessively high levels of circulating LDL → high blood cholesterol
- Leads to increased risk of developing CV disease or stroke at an early age
Name a side effect of statins affecting 1-5% of patients
Skeletal muscle toxicity:
- Myalgias
- Myopathy
- Rhabdomyolysis
Caused by common polymorphism is SLCOB1 gene causing the transporter responsible for the hepatic uptake of statins to work less effectively.
