MECHANISM OF METABOLISM - LIPID METABOLISM.pdf

This slide provides a brief description of Lipid metabolism.
Slide Title: Lipid Metabolism

Lipid metabolism involves the synthesis, breakdown, and interconversion of lipids in cells, crucial for energy storage, membrane structure, and signaling.

Importance of Lipids:

Concentrated energy source.
Essential for cell membranes and hormone synthesis.
Types of Lipids:

Fatty acids, triacylglycerols, phospholipids, sterols.
Fatty Acid Metabolism:

Synthesis: Acetyl-CoA to fatty acids (lipogenesis).
Breakdown: Fatty acid oxidation (lipolysis).
Triacylglycerol Metabolism:

Synthesis: Glycerol-3-phosphate esterification.
Breakdown: Hormone-sensitive lipase hydrolysis.
Phospholipid Metabolism:

Synthesis: Fatty acid addition to glycerol.
Turnover: Phospholipase-mediated hydrolysis.
Sterol Metabolism:

Synthesis: Acetyl-CoA to cholesterol (regulated by HMG-CoA reductase).
Regulation: Insulin and SREBPs control cholesterol synthesis.
Conclusion:

Lipid metabolism is vital for cellular function and homeostasis, dysregulation leads to metabolic disorders.
Understanding lipid metabolism aids in developing therapeutic interventions.
References available upon request.

1. LIPID METABOLISM
THE CLINICAL RELEVANCE OF
ESTIMATING SERUM CHOLESTEROL
AND TRIGLYCERIDE
1

2. INTRODUCTION
•Plasma/serumlipidshavetheiroriginfrom
eitherexogenousorendogenoussources.
•Foodprovidestheexogenoussourcewhiles
synthesisintheliverandtheintestine
providetheendogenoussource.
•Thesearemadeoffreefattyacids,
cholesterolesters,triglyceridesand
phospholipids
2

3. FUNCTIONS OF LIPIDS
•Cholesterol and phospholipids(lipid bilayer)
are vital structural components of cellular
membranes
•Cholesterol is the precursor of steroid
hormones and bile acids
•Absorption of dietary lipid is essential for the
absorption of fat-soluble vitamins.(ADEK)
3

4. LIPID PROFILE
•Lipidprofileisthemeasureofthevarious
lipidsfoundinthehumanblood
•Itisusedaspartofacardiacrisk
assessment tohelpdeterminean
individual'sriskofheartdiseaseandto
helpmakedecisionsaboutwhattreatment
maybebestifthereisborderlineorhigh
risk.
4

5. A LIPID PROFILE TYPICALLY
INCLUDES:
•Totalcholesterol—thistestmeasuresallofthecholesterolinall
thelipoproteinparticles.
•High-densitylipoproteincholesterol(HDL-C)—measuresthe
cholesterolinHDLparticles;oftencalled"goodcholesterol"
becauseitremovesexcesscholesterolandcarriesittotheliver
forremoval.
•Low-densitylipoproteincholesterol(LDL-C)—calculatesthe
cholesterolinLDLparticles;oftencalled"badcholesterol"
becauseitdepositsexcesscholesterolinwallsofbloodvessels,
whichcancontributetoatherosclerosis.Usually,theamountof
LDL-Ciscalculatedusingtheresultsoftotalcholesterol,HDL-C,
andtriglycerides.
•Triglycerides—measuresallthetriglyceridesinallthe
lipoproteinparticles;mostisintheverylow-densitylipoproteins
(VLDL).
5

6. CLINICAL IMPLICATIONS
AND SIGNIFICANCE
•The estimation of lipids (serum cholesterol/Triglycerides)
is considered to be significant in
oAtherosclerosis and relatedCoronary heart
diseases(angina&ischemicheartdisease)
ovariousliverdiseases.eg.Fattyliverdisease,
Hepatomegaly
oOthervarietyofclinicalfeaturesincludingcornealarcus,
Achillestendonthickening,xanthoma,xanthelasmaand
pancreatitis
6

7. SERUM ESTIMATION OF
CHOLESTEROL & TRIGLYCERIDE
Aim
Toestimatethetotalamountof
cholesterolorTriglyceridesintheblood.
7

8. PRINCIPLE (CHOLESTEROL)
•Cholesterolisenzymaticallyoxidisedbycholesteroloxidaseafter
hydrolysisofitsesterswithafungallipase.Hydrogenperoxidethus
releasedproducestheoxidativecouplingofphenolwith4-aminophenazone
(4AP)bymeansofareactioncatalysedbyperoxidase(POD).Theresultis
aredQuinoniminewithamaximumabsorptionat500-505nm.Theprinciple
isbasedonthefollowingreactionsystem
•Cholesterolesterslipase cholesterol+fattyacids
•Cholesterol+O
2 CHOD cholesten-3-one+H
2O
2
•H
2O
2+4-AP+phenolPOD4-(p-benzoquinoneimine)+4H
2O
8

9. PRINCIPLE (TRIGLYCERIDE)
•Sampletriglyceridesincubatedwithlipoproteinlipase(LPL),liberateglycerolandfree
fattyacids.Glycerolisconvertedtoglycerol-3-phosphate(G3P)andadenosine-5-
diphosphate(ADP)byglycerolkinaseandATP.Glycerol-3-phosphate(G3P)isthen
convertedbyglycerolphosphatedehydrogenase(GPDH)todihydroxyacetone
phosphate(DHAP)andhydrogenperoxide(H
2O
2).Inthelastreaction,hydrogen
peroxide(H
2O
2)reactswith4-aminophenazone(4-AP)andp-chlorophenolinpresence
ofperoxidase(POD)togivearedcoloureddye:
•TG LipaseGlycerol+fattyacids
•Glycerol+ATPGK Glycerol+Phosphate+ADP
•Glycerol-3-phosphate+O
2GPDH Glycerol+DihydroxyacetonePhosphate+H
2O
2
•2H
2O
2+4AP+chlorophenolPOD4H
2O
2+4-P-benzoquinoneimine
9

10. The Friedewald equation enables plasma LDL
cholesterol concentration to be calculated and
is often used in clinical laboratories:
LDL cholesterol =�??????�???????????? ??????ℎ??????????????????��??????�????????????−
?????????????????? ??????ℎ??????????????????��??????�????????????−
[????????????????????????????????????��????????????��]
2.2
VLDL=
????????????????????????????????????��????????????��
5
This equation makes certain assumptions,
namely that the patient is fasting and the
plasma triglyceride concentration does not
exceed 4.5 mmol/L (otherwise chylomicrons
make the equation inaccurate). 10

11. INTERPRETATION OF THE LIPID PROFILE
TOTAL CHOLESTEROL
Below 5.2 mmol/L Desirable
5.2-6.2 mmol/L borderline high
Above 6.2 mmol/L high
LDL-CHOLESTEROL
Below 2.6mmol/L Desirable
3.4-4.1 mmol/L Borderline high
4.1-4.9 mmol/L High
HDL-CHOLESTEROL
Below 1 mmol/L (men) Poor
Below 1.3 mmol/L (women) Poor
1.3-1.5 mmol/L Best
Above 1.5 mmol/L Better
TRIGLYCERIDES
Below 1.7 mmol/L Desirable
1.7-2.2 mmol/L Borderline high
2.3-5.6 mmol/L High
VLDL-CHOLESTEROL
>0.77 mmol/L High
11

12. PROCEDURE
1.TolabelledtesttubeCHandTG
2.Pipette2mlofworkingreagentprovided
intotherespectivetubes.
3.Add20µlofsamplepreparedaboveinto
bothtesttubes.Mixwellbyshakingthetest
tubegently.
4.Incubateatroomtemperatureforexactly
20minutes.
5.Mixwelland readtheoptical
density/absorbanceat500nm.
6.Youwillbeprovidedwithablanknearthe
spectrophotometer.
12

13. •ABSORBANCES FOR CHOLAND TRIG
STANDARDS
•CHO = 0.495
•TRIG = 0.265
•Standard Concentrations = 200mg/dl
13

14. Calculations:
A
(Sample)
A
(standard)
x 200 (Standard conc.) = mg/dL cholesterol in the
sample.
Conversion factor (cholesterol): mg/dL x 0.0258= mmol/L.
Conversion factor (TG): mg/dL x 0.0113= mmol/L.
TG TC
ABSORBANCE
CONCENTRATION
14

15. Questions
Your calculated concentrations from the above
test form part of the lipid profile results of a
patient who is undergoing a normal routine
check-up at the KNUST Hospital. Hence
Calculate the following parameters if HDL-CH =
1.4 mmol/L

1.VLDL
2.Non- HDL cholesterol
3.Cholesterol Ratio
4.LDL-CH
Comment and Interpret your result
15

16. THANK YOU
16
“Don’t suffer from imaginary
troubles”
- Some Wise Person