1. Lipid metabolism Presented by : Dr. M.R. Hamedinia
Assistant professor in Sabzevar university

2. Role of lipids
Nutrient stores Insulation Structure roles Carrier of the fat-soluble vitamins: A,D,K and E

3. Types of lipids
Lipids can be classified according to their structure. the two main classes are simple lipids and compound lipids.

4. simple lipids
The simple lipids are often referred to as neutral lipids and consist mainly of triacylglycerols. FFA + Glycerol triglyceride FFA Saturated unsaturated

5. Triacylglycerol: the fat tristearin (M10.2)

6. Triacylglycerols (fats)
The length of the fatty acid chain varies:
CH3 (CH2)n COOH
n = 12 is laurate
n = 14 is myristate
n = 16 is palmitate
n = 18 is stearate

7. Glycerol (three OH groups
Triacylglycerols (fats) C
+ H2O
OH + COOH O
Ester bond
Fatty acid (long hydrocarbon chain) C
CH3
Glycerol (three OH groups
bind fatty acids)

8. Triacylglycerol (fat) storage
 mmol in adipose tissue (lean man).
 300 mmol in skeletal muscle.
 0.5 mmol in blood plasma.
Energy:  560 MJ triaglycerol and  9 MJ glycogen (60 times more triacylglycerol).
Adipocytes
(Horowitz and Klein 2000)

9. A list of the most abundant fatty acids (M table 10.1)

10. Fatty acids are the most common type of lipids (M 10,1)

11. compound lipids
These are composed of a neutral fat in combination with other chemicals. The main groups are glycolipids, phosphoglycerides, and lipoproteins. HDL LDL

12. Phospholipids (M 10.6)

13. The hydrophilic groups of phospholipids (M10.7)

14. Sphingolipids (M page 323) often a hydrocarbon R group is attached to the NH2 as in ceramide

15. Glycoglycerolipids (M p 323)

16. Cholesterol (M10.9)

17. A scheme of a micelle and a membrane (M10.5)

18. PHOSPHOLIPID

20. chylomicronm
بزرگترین ذره های لیپوپروئینی هستند. توسط سلولهای اپی تلیال روده ای تولید می شوند. از راه سیستم لنفاوی وارد جریان خون می شوند. نیمه عمر پلاسمایی کمتر از یک ساعت دارند. شیلو میکرون اسیدهای چرب + گلیسرول

21. Fat Transport Transport of fats by plasma lipoproteins.
Composition (%)
Lipoprotein Fat Pl. Chol. Prot. Function
Chylomicr Trigl.: small bowel ð adipocyte
VLDL Trigl.: liver ð adipocyte
LDL Chol.: small bowel ð many sites
HDL Chol.: small bowel ð many sites
PL Phospholipid; Chol. Cholesterol; Prot. Protein; Chylomicr. Chylomicron. Trigl. Triglycerides
Hasson (1994)

26. Fat metabolism overview
Fatty acid
transporter
(FAT)
Activation
Albumin
Carnitine
Blood
b-oxidation
Acetyl CoA
NADH
Lipolysis
Glycerol
3 fatty acids
Krebs
cycle H+
ATP
Triacylglycerol (fat)
Mitochondrion
Fat cell
Muscle cell

27. Frayn et al. Essays biochem. 42: 89-103, 2006
Fat Ingestion
Insulin; splanchnic flow
DNL = de novo lipogenesis;
LPL = lipoprotein
lipase

29. Free fatty acids (low concentration)
Fat in blood
Apolipoprotein
Glycerol
Triacylglycerol
Albumin
Cholesterol ester
Cholesterol
Free fatty acids (low concentration)

30. Sites of fat metabolism
Triacylglycerol
Fatty acid transporter (FAT)
Skeletal muscle fibre
Krebs cycle
b-oxidation

33. b-oxidation CoA Activated fatty acid Carnitine acyltransfrease CoA
FADH2
Acyl-CoA dehydrogenase
Enoyl-CoA
Enoyl-CoA hydratase
Krebs cycle
Hydroxyacyl-CoA
NADH + H+
Hydroxyacyl-CoA dehydrogenase
Ketoacyl-CoA
Acyl-CoA acyltransferase
Acetyl-CoA
Mitochondrion

34. b-oxidation
Activities of b-oxidation enzymes are much higher in type I (slow twitch) than in type II (fast twitch) muscle fibres.
Enzyme activities of b-oxidation enzymes (in µmol g-1 min-1)
Enzyme
M. vastus M. soleus Heart
(type II) (type I)
Acyl CoA dehydrogenase
Enoyl CoA Hydratase
HAD
HAD Hydroxyacyl CoA dehydrogenase
Reichman and De Vivo (1991)

38. Lipolysis Exercise A, NA, TSH, ACTH, glucagon Insulin, GH, lactate - +
G-protein coupled
receptor
via PKA
HSL
HSL P
HSL Hormone-sensitive lipase

39. Fat Metabolism in Action

41. Percentage fat combustion decreases with intensity
Hohwü Christensen and Hansen (1939)

42. Absolute fat combustion
(van Loon et al. 2001)

43. Fat combustion decreases with intensity
Explanation:
Henneman’s size principle: Fast fibres (low fat metabolism) are only recruited during high intensity exercise.
Numerous hormones change with exercise and have an effect on lipolysis. Lactate inhibits lipolysis.
Intracellular regulatory mechanisms.
Conclusions: Almost impossible to explain.
Kandel et al. (1995)

44. Fat combustion increases with duration
Edwards et al. (1934)

45. Fat combustion increases with duration
Possible reasons:
Glycogenòð fat combustion must ñ if the energy consumption remains constant. Ingested glucose may preserve glycogen stores.
Lipolysis will increase and more FFA are in the blood.
Intramuscular regulatory mechanisms will contribute as well.
Conclusion: Fat combustion must increase if you are running out of glycogen.
FFA: “Free” fatty acids.

46. Fat combustion increases after training
Hurley et al. (1986)

47. Fat combustion increases after training
Possible reasons:
Endurance trained subject are glycogen savers: Glucose transporters (GLUT4)ñ, hexokinaseñ, glycogen synthaseñ, phosphorylase Û or ò. Lactate ò at given exercise intensityð lipolysisñð FFAñð fat combustionñ.
Endurance trained subject are fat spenders: Intramuscular triacylglycerol depotsñ, fatty acid binding proteinñ, b-oxidation enzyme activitiesñ, oxidative phosphorylation enzymesñð fat combustionñ.
Conclusion: Less glycolysis and more b-oxidation at given relative and absolute exercise intensities.

48. Fat combustion increases after training
Chronic stimulation switches metabolism from glycogen spending
to glycogen saving:
Henriksson et al.
(1986)
Oxidative phospho-rylation and fat metabolism increase
Glycolysis decreases
Chronic electrical stimulation (extreme endurance training model) ð oxidative phosphorylation ñ, glycolysis òðglycogen saver.

49. Fat combustion increases with duration
Possible reasons:
Pyruvate dehydrogenase: NADH + H+, acetyl CoA and ATP deactivate. The more “fuel” for the citrate cycle, the more pyruvate dehydrogenase is inhibited (unclear)
Carnitine acyltransferase is inhibited by Malonyl CoA. Malonyl CoAò with increasing duration (unclear).
Phosphofructokinase is inhibited by citrate. The more “fuel”(citrate) for the Krebs cycle, the more glycolysis is inhibited (unclear).
Conclusion: Fat combustion must be increased if less energy is available from glycogen. Peripheral lipolysis and several muscular enzymes may be control sites.

50. Fat combustion increases with duration
Possible reasons:
Glycogenòð fat combustion must ñ if the energy consumption remains constant. Ingested glucose may preserve glycogen stores.
Peripheral lipolysis: Lipolysisñ (due to increase in catecholamines, glucagonñ, insulinò)ð FFAñ with duration of exercise (due to increase in catecholamines, glucagonñ, insulinò)ð fat combustionñ.
FFA: “Free” fatty acids.

51. Fat combustion decreases with intensity
Brooks (1997)

52. Fat combustion decreases with intensity
Type I fibres:
Type II fibres:
Glycogen, glucose
Glycogen, glucose
Glycolysis
Glycolysis
Lactate
Pyruvate
Fats
Lactate
Pyruvate
Fats
b oxidation
b oxidation
Acetyl CoA
Acetyl CoA
Oxidative phosphorylation
Oxidative phosphorylation

53. Fat combustion decreases with intensity
Possible reasons:
Control of lipolysis: Lactateñð peripheral lipolysisòð FFAòð FFA combustionò. However, adrenalineñ and noradrenalineñ should increase lipolysis (lipolysis does not increase!).
Henneman size principle: Intensityñð percentage of type II fibres (very low in fat metabolism enzymes) recruitedñ ð fat combustion ò.
Pyruvate dehydrogenase (PDH): With increasing exercise intensity ADPñ, Ca2+ñ, pyruvateñð PDH activityñð carbohydrate combustionñ. However, NADH + H+ñ, Acetyl CoAñ with increasing exercise intensityð PDH activityòð carbohydrate combustionò (unclear).

54. Fat combustion decreases with intensity
Possible reasons:
Carnitin acyltransferase is inhibited by malonyl CoA. Effect of intensity on malonyl CoA unclear.
Citrateñ with exercise intensity ð phosphofructokinaseò. However, many other factors activate phosphofructokinase (unclear).
Conclusion: Effects of exercise intensity on fibre recruitment, peripheral lipolysis and intramuscular enzyme activity. Control still unclear.

55. Ergogenic Aids

56. Lipid supplementation
Intravenous infusion of lipid emulsion with heparin can increase fat oxidation by 30 % e.g. during high-intensity exercise. However, not practical.
Eating a high-fat meal (long-chain triacylglycerolsfats) before a competitions because of the slow digestion on delayed availability.
However, g of medium-chain triacylglycerols (8-10 carbons, MCTs) empty rapidly from the stomach. Ingestion of 30 g/h MCTs during 2 h of cycling diminished glycogen depletion and increased performance by 3 % (Van Zyl 1996).
Conclusion: Minor effect if ingested. However, potential role during expeditions and races in cold climates unclear.