TUTORIAL 7: LIPID METABOLISM

Name:____________________________ Tutorial Class: _______ Date:__________

TASK 1:
Complete the schematic representation (Appendix 1) to compare the Carnitine and Citrate
Shuttles.
For the Carnitine Shuttle identify
• Cellular sites a and b A: mitochondrial matrix B: cytosol
• Enzyme c : fatty acyl-CoA synthase
• Substrates/products d, e and f D: Fatty acid E: Carnitine F: fatty acyl-CoA
• Process g : beta oxidation
For the Citrate Shuttle identify
• Cellular sites a and b A: mitochondrial matrix B: cytosol
• Enzymes c and d C: citrate synthase D: citrate lyase
• Substrates/products e, f and g E: acetyl-CoA F: citrate G: malate
• Process h : lipogenesis

Shuttles get often mixed up!!

Carnitine shuttle Citrate shuttle

Role Transports activated FA/fatty acyl- Transports acetyl-CoA from the
CoA from the cytosol into the mitochondrial matrix into the cytosol for
mitochondrial matrix for βoxidation lipogenesis

John has muscle carnitine deficiency with clinical presentation of muscular weakness,
exercise intolerance and myalgia (muscle pain). Explain how his muscle fat metabolism is
affected upon intakes of a high fat diet or fasting. (AY0607Apr main, adapted) (6
marks)
carnitine is the carrier protein that transports activated fatty acids(fatty acyl CoA) from the
cytosol to the mitochondrial matrix for beta-oxidation. A high fat diet allows a flux of fatty
acids to be available as energy source while during fasting, catabolism of stored triglyceride
and a flux of fatty acids from adipose tissue to other tissues as fuel. Fatty acids are the
preferred fuel by resting skeletal and heart muscles. In both these states, muscular beta-
oxidation is affected due to carnitine deficiency.
 TASK 2: Formative Assessment

A molecule of tripalmitate (made up of one molecule of glycerol and three molecules of

palmitic acid, C16:0) is catabolized for energy. Show the detailed energetics and calculate
the ATP yield per C atom. (16 marks)

7 cycles

NADH: 7 x 2.5 = 17.5 ATP

Grand total= 336.5 ATP

ATP Yield per carbon atom = 6.6

Describe the intestinal pathway of triglyceride resynthesis which is active in entherocytes in

the post-meal state. Identify how the substrates are first transported into the enterocytes from
the lumen. (10 marks)
long chain fatty acids are transported into the enterocytes via facilitated diffusion while
2-monoglycerides are transported into the enterocytes via simple diffusion. The intestinal
pathway of TG resynthesis is that fatty acids are combines with CoenzymeA to form activated
fatty acyl CoA. ATP become AMP + PPi. The enzyme involved is acyl CoA synthetase. 2
monoglycerides are combines with fatty acyl CoA to form 1,2-diglyceride which combines
with fatty acyl CoS to form triglycerides. This happens in the endoplasmic reticulum.

Explain why diabetics with poor blood glucose control are at risk of ketosis. State the
physiological effects of ketosis. (10 marks)
In diabetics with poor blood glucose control, there is insufficient insulin action. Blood
glucose is high because glucose cannot enter cells. As a result, cells in starvation mode break
down fat for fuel (lipolysis). Beta-oxidation of fat produces large amounts of acetyl CoA. They
cannot enter the TCA Cycle due to oxaloacetate deficiency and are diverted to form ketone
bodies leading to ketosis (physiological impact of this condition – ketosis) the drop in blood
pH is ketoacidosis, a life-threatening condition ketonuria lead to dehydration with electrolyte
imbalance/depletion. Ketonemia is just ketone in the blood but if it continues then is
ketoacidosis

Explain the term “reverse cholesterol transport”. Describe the two pathways of reverse
cholesterol transport. (10 marks)
Reverse cholesterol transport is the transportation of cholesterol back to the liver. HDL
collects cholesterol from peripheral tissues. The enzyme lecithin-cholesterol acyl transferase
(LCAT) converts it into cholesterol ester. In the direct pathway, HDL is taken in by the liver as
intact particles. The cholesterol esters is removed and the HDL is re-secreted in a process
called retroendocytosis. In the indirect pathway, HDL releases cholesterol to VLDL in
exchange for TG. Catalyzed b cholesterol ester transfer protein (CETP) CLDL becomes IDL
and eventually IDL. The cholesterol reaches the liver when LDL is taken up.

Common qns

 Describe the fates of lipoprotein

 Compare the fate of chylomicron and HDL