LECTURE 2 (Lipid Metabolism) Flashcards
What are Lipids?
Macromolecules that contain carbon, hydrogen and oxygen atoms
[however, unlike carbohydrates lipids contain a lower proportion of oxygen]
what are examples of lipids?
- Fatty acids
- Triglycerides
- Cholesterol
- Phospholipids
- Steroids
What is a fatty acid composed of?
Carboxylic group and hydrocarbon chain
What is the bond between a glycerol molecule and a fatty acid called?
An ester bond
Describe the enzymes involved in fat digestion
Fat breakdown begins in the mouth with LINGUAL LIPASE -> Partially digested lipids are broken down by GASTRIC LIPASE in the stomach -> Fat droplets and acidity stimulate small intestinal cells activation of CHOLECYSTOKININ (CKK) and SECRETIN
Describe fat digestion in the mouth
- Mechanical digestion
- Mixing with saliva
- Limited enzymatic digestion (lingual lipase)
Describe fat digestion in the stomach
- Mixing/churning
- Limited enzymatic digestion (gastric lipase)
Describe fat digestion in the small intestine
- Emulsification (bile)
- Enzymatic digestion (pancreatic lipases)
- Micelles help with absorption
What does Cholecystokinin (CKK) do?
- Bile production and secretion
- Pancreatic juice release (contains pancreatic lipase)
What does Secretin do?
- Bicarbonate secretion from the pancreas
- Increase pH
What are the properties of Pancreatic lipase?
- Secreted by the pancreas and transferred to the duodenum
- Participates in the hydrolysis and digestion of fat, cholesterol esters and fat-soluble vitamins
Where are monoglycerides and fatty acids absorbed mainly?
In proximal 2/3 of the jejunum
Where are bile salts absorbed?
In the terminal ileum and enter portal circulation (ENTEROHEPATIC CIRCULATION)
[95% are absorbed and recycled, 5% excreted in stool]
What are the properties of Bile?
- Produced in liver
- Stored in gallbladder
- Secreted into duodenum after meal
- Consists of water, phospholipids and electrolytes
What is the difference between Bile salts and Bilirubin?
Bile salts = necessary for lipid absorption
Bilirubin = mode of excretion from body
What is Emulsification?
A process in which large lipid globules are broken down into several small lipid globules
What is the importance of Emulsification?
Mediated by bile salts which surround lipid particles and dissolve them in water creating a larger surface area for PANCREATIC LIPASE to work
How are Bile acids synthesised?
Bile salts are synthesised from bile acids (Cholic acid, Chenodeoxycholic acid) synthesised from Cholesterol in liver -> Bile acids are conjugated with TAURINE (organic acid) and GLYCINE which are hydrophilic -> One end is hydrophobic and the other end is hydrophilic
What are the functions of Bile Salts?
- Emulsificaton of fats
- Excretion of cholesterol
- Antimicrobial
Explain how Bile salts excrete cholesterol
Cholesterol is not soluble in water -> cannot be excreted in urine -> Incorporated into CONJUGATED BILE which is water soluble -> excreted in stool
Explain how Bile salts are antimicrobial
Small intestine has few bacteria -> Loss of bile salts leads to bacterial overgrowth (in liver diseases) -> Bile salts disrupt bacterial cell membrane
How are fatty acids absorbed into the lymph bloodstream?
In GI TRACT fatty acids are converted into TRIGLYCERIDES by combining with GLYCEROL -> Triglycerides are combined with lipoprotein molecules called CHYLOMICRONS by intestinal cells -> Chylomicrons + lymphatic fluid form a milky white CHYLE inside lymph vessels -> Chylomicrons are secreted into the lymph bloodstream
How is cholesterol absorbed into the lymph bloodstream?
Cholesterol is converted into CHOLESTERYL ESTERS in enterocytes via ACYL-COA CHOLESTEROL ACYLTRANSFERASE (ACAT) -> Cholesterol esters are packaged into CHYLOMICRONS by intestinal cells -> To lymph bloodstream
What is found within a Chylomicron?
- Triglycerides
- Cholesteryl esters
- Vitamins A, D, E & K
What is Cystic Fibrosis?
An autosomal recessive genetic defect in the CFTR (Cystic Fibrosis Transmembrane Regulator) gene on chromosome 7 leading to a misfolded protein resulting in thick, sticky mucus in lungs and GI tract
CAUSES:
Misfolded protein is retained in RER and not transported to cell membrane -> Causing decreased Cl- and H2O secretion -> CFTR ion transporter is supposed to secrete Cl- in lungs & GI tract and reabsorbs Cl- in sweat glands
SYMPTOMS:
- Recurrent respiratory infections
- Failure to thrive
- Meconium ileus (bowel occlusion due to thick and sticky stool)
- Biliary disease (Bile duct obstruction, pale or clay coloured stool, elevated LFTs, hepatomegaly, cirrhosis, gallstones)
- Infertility (95% males infertile, SUBFERTILITY in females)
- Digital clubbing
- Nasal polyps
DIAGNOSIS:
- Sweat chloride test
- DNA testing (If sweat chloride test is abnormal)
- Nasal transepithelial potential difference (if mild symptoms + -ve sweat test)
TREATMENT:
- Chest physiotherapy
- Albuterol
- Aerosolised DORNASE ALFA (Dnase)
- Hypertonic inhaled saline
- N-acetylcysteine (cleaves disulphide bonds in mucous glycoproteins -> can induce bronchospasm in some children)
- Enzyme that breaks down DNA strands in airway secretions -> hydrolyses DNA present in sputum/mucous in CF patients -> reduces viscosity & prevents airway infection & damage to lung parenchyma
PROGNOSIS:
- avg life span 37 years
- death from lung complications
What is the common cause of chronic lung disease in children?
Cystic Fibrosis
What is the CFTR function in Epithelial cells and Sweat glands?
EPITHELIAL CELL FUNCTION
- Pumps Cl- out of epithelial cells against concentration gradient (uses ATP)
- Creates a membrane potential that draws out Na/H2O -> hydrates mucosal surface in lungs & GI
SWEAT GLANDS
- Removes NaCl from sweat (makes sweat hypotonic) -> CF patients have high NaCl in sweat
What do thick mucous in lungs of CF patients cause?
- Recurrent pulmonary infections
- Chronic bronchitis
- Bronchiectasis
What do which mucous in GI tract of CF patients cause?
- Impaired flow of bile and pancreatic secretions (chronic pancreatitis, CF-related diabetes)
- Malabsorption especially fats
- Loss of fat-soluble vitamin (ADEK)
- Steatorrhea (frequent, foul-smelling, greasy, floating stools)
Describe the Sweat chloride test
PILOCARPINE GAUZE is placed on skin -> small electrical current drives pilocarpine into skin -> sweating -> sweat collected on filter paper -> chloride content analysed
-> high chloride level suggests CF
Describe the Nasal transepithelial potential difference
Measures nasal voltage -> CF patients have more -ve voltage due to abnormal sodium processing
What is the treatment for patients with Phe508 deletion?
- LUMACAFTOR = corrects misfolded proteins and improves their transport to cell surface
- IVACAFTOR = opens cl- channels -> improved chloride transport
What are other options for treatments of CF?
- Exacerbations treated with antibiotics (AZITHROMYCIN used as anti-inflammatory agent)
- Ibuprofen slows disease progression
- Lung transplantation
- Pancreatic enzyme treatment
- Vitamins (ADEK)
- Vaccinations
Describe newborn screening for CF
- Increased blood levels of IMMUNOREACTIVE TRYPSINOGEN (IRT)
- TRYPSINOGEN is a zymogen synthesised in pancreas
- Blood test if +ve sweat test
