LECTURE 2 (Lipid Metabolism)

Question 1

What are Lipids?

Answer 1

Macromolecules that contain carbon, hydrogen and oxygen atoms

[however, unlike carbohydrates lipids contain a lower proportion of oxygen]

Question 2

what are examples of lipids?

Answer 2

• Fatty acids
• Triglycerides
• Cholesterol
• Phospholipids
• Steroids

Question 3

What is a fatty acid composed of?

Answer 3

Carboxylic group and hydrocarbon chain

Question 4

What is the bond between a glycerol molecule and a fatty acid called?

Answer 4

An ester bond

Question 5

Describe the enzymes involved in fat digestion

Answer 5

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

Question 6

Describe fat digestion in the mouth

Answer 6

• Mechanical digestion
• Mixing with saliva
• Limited enzymatic digestion (lingual lipase)

Question 7

Describe fat digestion in the stomach

Answer 7

• Mixing/churning
• Limited enzymatic digestion (gastric lipase)

Question 8

Describe fat digestion in the small intestine

Answer 8

• Emulsification (bile)
• Enzymatic digestion (pancreatic lipases)
• Micelles help with absorption

Question 9

What does Cholecystokinin (CKK) do?

Answer 9

• Bile production and secretion
• Pancreatic juice release (contains pancreatic lipase)

Question 10

What does Secretin do?

Answer 10

• Bicarbonate secretion from the pancreas
• Increase pH

Question 11

What are the properties of Pancreatic lipase?

Answer 11

• Secreted by the pancreas and transferred to the duodenum
• Participates in the hydrolysis and digestion of fat, cholesterol esters and fat-soluble vitamins

Question 12

Where are monoglycerides and fatty acids absorbed mainly?

Answer 12

In proximal 2/3 of the jejunum

Question 13

Where are bile salts absorbed?

Answer 13

In the terminal ileum and enter portal circulation (ENTEROHEPATIC CIRCULATION)

[95% are absorbed and recycled, 5% excreted in stool]

Question 14

What are the properties of Bile?

Answer 14

• Produced in liver
• Stored in gallbladder
• Secreted into duodenum after meal
• Consists of water, phospholipids and electrolytes

Question 15

What is the difference between Bile salts and Bilirubin?

Answer 15

Bile salts = necessary for lipid absorption

Bilirubin = mode of excretion from body

Question 16

What is Emulsification?

Answer 16

A process in which large lipid globules are broken down into several small lipid globules

Question 17

What is the importance of Emulsification?

Answer 17

Mediated by bile salts which surround lipid particles and dissolve them in water creating a larger surface area for PANCREATIC LIPASE to work

Question 18

How are Bile acids synthesised?

Answer 18

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

Question 19

What are the functions of Bile Salts?

Answer 19

• Emulsificaton of fats
• Excretion of cholesterol
• Antimicrobial

Question 20

Explain how Bile salts excrete cholesterol

Answer 20

Cholesterol is not soluble in water -> cannot be excreted in urine -> Incorporated into CONJUGATED BILE which is water soluble -> excreted in stool

Question 21

Explain how Bile salts are antimicrobial

Answer 21

Small intestine has few bacteria -> Loss of bile salts leads to bacterial overgrowth (in liver diseases) -> Bile salts disrupt bacterial cell membrane

Question 22

How are fatty acids absorbed into the lymph bloodstream?

Answer 22

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

Question 23

How is cholesterol absorbed into the lymph bloodstream?

Answer 23

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

Question 24

What is found within a Chylomicron?

Answer 24

• Triglycerides
• Cholesteryl esters
• Vitamins A, D, E & K

Question 25

What is Cystic Fibrosis?

Answer 25

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

Question 26

What is the common cause of chronic lung disease in children?

Answer 26

Cystic Fibrosis

Question 27

What is the CFTR function in Epithelial cells and Sweat glands?

Answer 27

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

Question 28

What do thick mucous in lungs of CF patients cause?

Answer 28

- Recurrent pulmonary infections - Chronic bronchitis - Bronchiectasis

Question 29

What do which mucous in GI tract of CF patients cause?

Answer 29

- 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)

Question 30

Describe the Sweat chloride test

Answer 30

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

Question 31

Describe the Nasal transepithelial potential difference

Answer 31

Measures nasal voltage -> CF patients have more -ve voltage due to abnormal sodium processing

Question 32

What is the treatment for patients with Phe508 deletion?

Answer 32

- LUMACAFTOR = corrects misfolded proteins and improves their transport to cell surface - IVACAFTOR = opens cl- channels -> improved chloride transport

Question 33

What are other options for treatments of CF?

Answer 33

- Exacerbations treated with antibiotics (AZITHROMYCIN used as anti-inflammatory agent) - Ibuprofen slows disease progression - Lung transplantation - Pancreatic enzyme treatment - Vitamins (ADEK) - Vaccinations

Question 34

Describe newborn screening for CF

Answer 34

- Increased blood levels of IMMUNOREACTIVE TRYPSINOGEN (IRT) - TRYPSINOGEN is a zymogen synthesised in pancreas - Blood test if +ve sweat test