リポタンパク質
リポタンパク質の構成
中性脂肪(トリグリセリド)やコレステロールといった疎水性の脂質はそのままの状態では血中を移動することができない。
このため、親水性のアポタンパク質やリン脂質と結合してリポタンパク質と呼ばれる親水性の複合体を形成して血中を移動する。
リポタンパク質の種類
リポタンパク質は組成によって大きさや比重が異なり、カイロミクロン(ChyloMicron:CM)・VLDL(超低比重リポタンパク質:Very Low Density Lipoprotein)・IDL(中間比重リポタンパク質:Intermediate-Density Lipoprotein)・LDL(低比重リポタンパク質:Low Density Lipoprotein)・HDL(高比重リポタンパク質:High Density Lipoprotein)の5種類に分けられる。
大きさや比重や組成の割合は上記の図を参考にして頂きたい。
リポタンパク質の割合と血清外観の関係
血中にカイロミクロンが増加すると血清の上部にクリーム層ができる。
血中にVLDLやLDLが増加すると血清が白濁化する。
血中にコレステロールが増加すると血清は透明となる。
乳び血清
乳白色に混濁した血清を指す。
中性脂肪を多く含むカイロミクロンやVLDLが増加していることを示す。
リポタンパク質の代謝
外因性経路
食事由来の外因性脂質(中性脂肪を多く含む)は小腸から吸収されて、小腸で形成されたアポリポタンパク質B48(ApoB-48)と結合してカイロミクロンを形成する。
カイロミクロンは「小腸のリンパ管→胸管→左鎖骨下静脈」を辿り全身に運ばれる。
脂肪組織の毛細血管内皮細胞表面にはLPL(リポ蛋白リパーゼ)が存在しており、カイロミクロンが含んでいる中性脂肪の一部がLPLによってグリセロールと脂肪酸に分解される。
そして、分解されたものが脂肪細胞に取り込まれて中性脂肪へと再合成されて貯蓄される。
LPLによって一部が分解されたカイロミクロンはカイロミクロンレムナントとなり、肝臓に存在するカイロミクロンレムナント受容体に結合して肝臓に取り込まれる。
内因性経路
肝臓では内因性脂質の製造が行われており、製造された中性脂肪やコレステロールといった内因性脂質は肝臓で生成されたアポリポタンパク質B100(ApoB-100)と結合してVLDLとなってから血中に分泌される。
VLDLはLPLによって含んでいる中性脂肪の一部が分解されてIDLとなる。
また、このときにHDLも合成される。
IDLは肝臓に存在する肝性トリグリセリドリパーゼ(HTGL)によってさらに中性脂肪が分解されてLDLとなる。
LDLはコレステロールを末梢組織に運搬する役割を持つので、LDLコレステロールは悪玉コレステロールと呼ばれる。
これに対して、HDLは末梢組織にとって余分なコレステロールを引き抜いて肝臓に回収させる役割を持つので、HDLコレステロールは善玉コレステロールと呼ばれる。
インスリンとLPLの関係
インスリンにはLPL(リポ蛋白リパーゼ)の活性を亢進させる作用がある。
また、LPLがVLDLやカイロミクロンを遊離脂肪酸とグリセロールに分解する際にその表面生成物からHDLが合成される。
このため、インスリン抵抗性が生じるとLPLの活性が低下してVLDLとカイロミクロンが血中に増加するのに加えてHDLが血中から減少する。つまり、中性脂肪(トリグリセリド)の値が増加して、HDLコレステロールの値が減少することになるのである。
通常時と飢餓時の脂質代謝
通常時の脂質代謝
通常時は肝臓において内因性脂質の製造が行われている。
解糖系途中の代謝産物であるジヒドロキシアセトンリン酸がアセチルCoAから生産された脂肪酸と結合してトリグリセリド(中性脂肪)が合成される。
また、アセチルCoAからコレステロール合成の流れを経てコレステロールが合成される。
このようにしてできた内因性脂質(トリグリセリド・コレステロール)はアポリポタンパク質(ApoB-100)と結合してリポタンパク質(VLDL)を形成する。
VLDLは脂肪組織に運ばれて、中性脂肪は脂肪細胞に蓄えられることとなる。
飢餓時の脂質代謝
通常時、肝臓は内因性脂質を製造してエネルギーを貯蓄するように働いていたが、飢餓時には貯蓄していたエネルギーを放出させてケトン体を製造してエネルギー消費組織に送り込むような働きをするようになる。
内臓脂肪として存在する脂肪細胞から遊離脂肪酸が放出されると、その脂肪酸を肝臓は取り込んでβ酸化を行ってアセチルCoAに変換する。
変換したアセチルCoAからケトン体を合成して筋肉や脳といったエネルギー消費組織に届けられる。
脂質異常症
血中の脂質の値が基準値から外れた状態を脂質異常症と呼ぶ。
総コレステロール(TC)は善玉コレステロールであるHDLコレステロールも含むため、総コレステロール(TC)が多いからといって脂質異常症であるかは分からない。
Fridewald式
LDL-Cを直接求める直接法で測定した検査値には測定精度上の問題が少なくないことが知られている。
このため、LDL-CはFriedewald式を用いて算出することになっている。
Friedewald式を適用するためにはカイロミクロンが存在しない空腹時に産出する必要がある。
また、Friedewald式において中間産物であるIDLは少数しか存在していないので考慮されていないか検査上LDLと区別されていない。
そして、空腹時には血清トリグリセリド:TgのほとんどがVLDLに存在していて、VLDLはトリグリセリドとコレステロールを5:1の割合で含むという前提のもと作られている。
この前提のためにトリグリセリド値が高くなればなるほどLDL-Cが過少評価されるという誤差が生じてしまうので、トリグリセリド値が400mg/dL以上の場合にはnon-HDLコレステロールを算出してLDLコレステロールの代わりに評価することになっている。
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