Lehninger Principles of Biochemistry 5/e

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1 CHAPTER 17 Fatty Acid Catabolism 지방산의이화 1. digestion, mobilization, transport of fats ( 지방의소화, 방출, 운반 ) 2. Oxidation of fatty acids ( 지방산산화 ) 3. ketone bodies ( 케톤체 ) 2008 W. H. Freeman and Company

2 Processing of food lipids in vertebrate 척추동물에서의식이지질의처리과정

3 Chylomicron VLDL, LDL, HDL, VHDL 암죽미립의분자구조 아포지단백질 인지질 콜레스테롤 트리아실글리세롤과콜레스테롤

4 Mobilization of tricacylglycerol in fat cells 지방조직에저장된트리글리세롤의방출

5 Entry of glycerol into glycolytic pathway 글리세롤이당분해경로로들어가는경로 3 인산글리세롤탈수소효소 글리세롤인산화효소 3- 인산 L- 글리세롤 글리세롤 인산다이히드록시아세톤 인산삼탄당이성화효소 3- 인산 D- 글레세르알데히드

6 Conversion of fatty acid to fatty acyl -CoA on the outer mit memb 지방산이지방산아실 CoA 로의전환 카복실이온이공격하여지방산아실아데닐산과피로인산이생성. 피로인산은즉시두분자의 Pi 로가수분해됨 아실 CoA 합성효소 무기피로인산염분해효소 아실 CoA 합성효소 CoA 의씨올기가공격하여 AMP 를떼내고대신결합하여아실 CoA 생성

7 Acyl carnitine transporter for entry of fatty acid into mitochondria 아실카르니틴수송체에의한지방산의미트콘드리아로의이동 (C14 보다큰자유지방산 ) C12 이하는자유롭게통과 ) 카르니틴 ( 아실기결합자리 )

8 overview for fatty acid Oxidation 지방산산화개괄 Mammalian heart and liver- major sites (80%) cytosol

9 팔미토일 CoA 트랜스델타 2 에노일 CoA 엘베타하이드록시아실 CoA 베타케토아실 CoA ß oxidation 베타산화 아실 CoA ( 미리스토일 CoA) 아세틸 CoA

10 3 AD(acyl CoA de..); VLC AD(very long chain) 2~18C MC( medium chain)ad 4~14C SCAD (short chain) 4~8C membrane enzyme connecting to ETF (electron transferring flavoprotein) on mit trans to L cis to D stereospecific

11 L form specific

13 베타탄소에있는카보닐작용을카복실기에소개하는보존된반응순서

15 palmitate to CO 2 and H 2 O 9,800 kj/mol (standard) 106ATP x 30.5 kj/mol =3,230 kj/mol =>33% (physiology) >60%

16 for double bond β γ 단일불포화지방산의산화 키스델타 3 도데세노일 CoA 델타 3, 델타 2 에노일 CoA 이성화효소 트랜스델타 2 도데세노일 CoA

17 for double bond α-β 다불포화지방산의산화

20 oxidation of odd number fatty acid 홀수지방산산화

22 보조효소비 12 메틸마로닐 CoA 변위효소

24 Role of coenzyme B 12 (cofactor form of Vitamin B 12 ) X- alkyl or substituted alkyl

25 Chemical structure of B 12 The bond between CH 2 & Co (cobalt) is weak. Allowing carbon radical 탄소라디칼

28 regulation of fatty acid synthesis and degradation 지방산의합성과분해조절 ACC (acetyl CoA carboxylase) carnitine acyl transferase I PPAR (peroxisome proliferator activated receptors) Transcriptional regulation of enzymes for FA oxidation; neonatal transition (glu, lactate in fetal to FA), and endured exercisez β hydroyacyl CoA dehydrogenase; inhibited by high [NADH} Thiolase; inhibited by high [acetyl CoA]

29 comparison of β oxidation Peroxisome 과산화소체 / 글리옥시솜 -a major site in plant

30 triacylglycerol as glucose source in seeds 종자에서포도당공급원이되는트리아실글리세롤

31 variation in β oxidation enzymes 베타산화효소의다양성 among organisms and organelles * MFP (multifunctional enzyme) 그람양성균과미토콘드리아의짧은사슬특이시스템

32 그람음성균

33 미토콘드리아의긴사슬특이시스템

34 식물의과산화소체및글리옥시솜체

36 ω oxidation 세포질세망에서지방산오메가산화 in endoplasmic reticulum (liver, kidney) 10, 12C

39 α oxidation 과산화소체의가지사슬지방산의알파산화 for branched fatty acid (phytanic acid) in peroxisome

42 Ketone bodies 케톤체 아세톤 mitochondria matrix (liver) formed when fatty acid oxidation more active than glycolysis (little [oxaloacetate]) [acetyl CoA] available [CoA] 아세토아세트산 디베타하이드록시부티르산

43 formation of ketone bodies from acetyl CoA

46 Conversion of D-β hydroxbutyrate into acetyl CoA synthesized in liver passes into blood, then into other tissues (heart, muscle, renal cortex, starved brain) converted into acetyl CoA

47 Ketone bodies are overproduced in Diabetes and during starvation promoting gluconeogenesis slowing TCA cycle enhancing ketone body formation

48 Acidosis high [acetoacetate + D-β hydroxbutyrate] in blood (called Ketosis) like untreated diabetes lower ph causing coma and even death

Lehninger Principles of Biochemistry 5/e

David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition CHAPTER 17 Fatty Acid Catabolism 2008 W. H. Freeman and Company Chap. 17. Fatty acid oxidation 지방산의소화, 동원그리고운반 1. 식이성지방