Lipid Metabolism

SEQ: Describe lipid metabolism under fasting state. (10 marks)

MODEL ANSWER:

No.	Details	Marks
1.	During fasting, there are many changes in the body and blood in the following: i.      nutrient storage, supply and levels; ii.     hormone secretions and levels; iii.    blood pH; iv.    Usage of alternative energy resources v.     energy storage, supply and levels;	2
2.	Order of usage of energy resources within the body: i.      Glucose (0-4 hrs), ii.     Glycogen (during sleep), iii.    Proteins (by day 3), and iv.    Lipids (from day 3 onward) v.     Ketones	2
3.	Chemical processes & pathways (catabolism): a.     glycolysis, b.    proteolysis, c.     lipolysis, d.    glycogenolysis, e.     b-oxidation f.     TCA cycle g.    ETC	2
4.	Lipid metabolism in fasting: i.      Hyperglycaemic hormones: Increase ii.     Insulin: Decrease iii.    Exogenous lipoprotein metabolism: No iv.    Endogenous lipoprotein metabolism: Yes v.     Fat mobilization (from adipose tissue): Active vi.    Carnitine shuttle: Active vii.   b-oxidation: Very active viii.  TCA cycle: Active ix.    ETC: Active x.     Ketogenesis: Very active xi.    Ketolysis: Active xii.   Gluconeogenesis (from glycerol): Yes	2
5.	Effects of lipid metabolism during fasting (fasting lipid profile): i.      Blood glucose: low-normal ii.     Blood free fatty acids (FFA): high iii.    Blood ketones: high, acidic --> ketoacidosis iv.    Blood pH: metabolic acidosis, due to high ketones v.     Blood amino acids: low vi.    Blood glycogen: nil	2

STUDENTS' PROBLEMS WITH THIS QUESTION

Wrong answers

Lipid Digestion

Exogenous Lipoprotein Metabolism (Chylomicron metabolism)

Exogenous + Endogenous Lipoprotein Metabolism (CM + VLDL metabolism)

Lipid Digestion: Dietary fat will be combined with bile salt and formed into the water soluble micelles. Then, micelles will be transported to the intestinal absorption site. Once the micelles already absorbed across the intestinal mucosal cell, dietary fat will be reesterified to form into the triglyceride and also cholesterol esters and travels in the blood plasma.

Exogenous Lipoprotein Metabolism: Chylomicron will be released into the blood circulation by travels in lymphatic duct and thoracic duct. Chylomicron will be hydrolysed by the enzyme lipoprotein lipase (LPL) to become monoglyceride, diglyceride and free fatty acid to be uptake by the cells. While chylomicron remnant be uptake by the liver to undergo delipidation to be used to synthesize new lipoprotein and building of plasma membrane.

Gluconeogenesis: Under fasting state, lipid undergo gluconeogenesis to supply glucose. b-oxidation of lipid produce acetyl CoA. Under fasting state, lipid undergo lipolysis, and FFA undergo b-oxidation. Lipid is first breakdown and transfer into mitochondria matrix to form oxaloacetate (OAA). OAA convert to citrate and transported into cytosol. In cytosol, OAA is converted back by citrate. Citrate convert into phosphoenolpyruvate (PEP) by PEP carboxykinase. PEP is converted into fructose-1,6-biphosphate by fructose-1,6-biphosphatase. Fructose-1,6-biphosphate dephosphorylate bt fructose-6-phosphatase into fructose-6-phosphate. Frutose-6-phosphate convert into glucose-6-phosphate by phosphoglucomutase. Glucose-6-phosphate dephosphorylated into glucose by glucose-6-synthase. Glucose enter glycolysis to supply energy.

When fasting, glucose stores are depleted. Other sources of energy are needed by the body such as protein, fatty acids, and ketone bodies. Gluconeogenesis, glycogenolysis are all in the action at higher levels. Glucagon stimulate the secretion of fatty acid lipase to degrade fatty acid. This is termed lipolysis. This leads to increase in free fatty acids, that is degraded  to lactic acid and used in gluconeogenesis for ketone body generation. Ketone bodies are alkaline in nature and this leads to ketoalkalosis. Gluconeogenesis takes place 90% in the liver and 10% in the kidney. Lipolysis increase which leads to increase blood fatty acid and form alkaline urine.

Ambiguous answers

Fatty acyl-CoA will undergo gluconeogenesis to produce glucose.

Gluconeogenesis is process to produce glucose from non carbohydrate molecules.

During fasting, glucose will be breakdown first followed up by lipid breakdown, then only goes to protein breakdown.

Meaningless answers

Lipid –[fasting]--> FA + Glycogen (should be Glycerol)

Lipid will undergo gluconeogenesis

Lipid is hydrolysed to acetyl CoA

Fatty acids with short chain is transported directly into the blood circulation where it binds to ammonia and is stored as triglycerides.

Fatty acids with long chain and glycerol absorbed into the lacteal, then flows into the thoracic duct and finally into the blood.

Fatty acids is added with vitamen A, D, E and K to produce chylomicrons.

The chylomicrons are broken down into fatty acid and glycerol.

Remnents of the chylomicrons are stored in the liver.

Glucose will undergo glycolysis to produce high energy which is ATP.

b-oxidation itself can produce ATP.

Breakdown on lipid into fatty acid and triglycerides.

Lipid ---> FFA  +  TG [this is wrong] vs. Lipid ---> FFA  + Glycerol [this is correct]