Apolipoproteiini B48:n merkitys . Neurofibromiini-1.n merkitys

 ApolipoproteiiniB kylomikroneissa  lie   herkkä vaste ravintosisältöön.  Kylomikroit taas käyttävät imusuonitietä ja ehtivät kiertää  niin keuhkoverenkierron kuin aivoverenkierronkin ensen kuin jäänteet kertyvät maksaan ja käyvät  läpi endosomaalisen lajittelun ja  ehkä hajoitetaan.
Imusuonitie onkin takuu siitä, että jopa aivot  ja keuhkot saavat  tarvitsemiaan rasva-aineita nopeasti.




https://www.ncbi.nlm.nih.gov/pubmed/24938018

Adv Clin Chem. 2014;64:117-77.

Apolipoproteiini B48 on ainutlaatuinen kylomikroniaineenvaihdunnan merkitsijä 

ApoB-48 tiedetään  ainoaksi spesifiseksi merkitsijäksi suolen kylomikronipartikkeleista. Aminohapposekvenssiltään apoB-48  edustaa 48%:a  apoB-100:n  alkusekvenssistä. ApoB-48 syntetisoituu ihmisellä vain suolessa, kun taas apoB-100 syntetisoituu primääristi maksassa. Sentakia  soveltuu apoB-48  mitä asianmukaisimmin postprandiaalisen  kylomikroniaineenvaihdunnan kardiovaskulaarisiin ja nutritionaalisiin tutkimuksiin. Tässä  katsauksessa pohditaan viime vuosien löytöjä ja  Zilversmitin  30 vuotta aiemmin esittämää  teoriaa postprandiaalisesta hyperlipidemiasta. Kuvataan apoB-48:n  ominaisuudet ja osa kylomikronien apolipoproteiinina, varsinkin kylomikronien jäännöslipoproteiinien merkitsijänä.   Keskustellaan myös sopivien analyyttisten metodien  tarpeesta  apoB-48:n mittaamiseksi. 

• Apolipoprotein B-48: a unique marker of chylomicron metabolism.

• Nakajima K, Nagamine T, Fujita MQ, Ai M, Tanaka A, Schaefer E. Abstract

• Apolipoprotein B-48 (apoB-48) is known to be the only specific marker of intestinal chy lomicron particles. The amino acid sequence of apoB-48 represents 48% of the initial sequence of apoB-100. ApoB-48 is synthesized only by the intestine in humans, while apoB-100 is synthesized primarily by the liver. Therefore, apoB-48 is a most appropriate biomarker for cardiovascular and nutritional investigation of postprandial chylomicron metabolism. In this review article, we discussed the difference between the recent findings and Zilversmit's proposal of postprandial hyperlipidemia reported over 30 years ago. The characteristics and role of apoB-48 as an apolipoprotein in chylomicrons, especially as a marker of chylomicron remnant lipoproteins, are described. The need for appropriate analytical methods to measure apoB-48 is also discussed.

Wikipediasta löytyy mielenkiintoinen yhteenveto, josta  sitaatti:
https://en.wikipedia.org/wiki/Apolipoprotein_B

Sitaatti: 

"Molecular biology

The protein occurs in the plasma in 2 main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the small intestine, the second by the liver.^[10] ApoB-100 is the largest of the apoB group of proteins, consisting of 4563 amino acids.^[10] Both isoforms are coded by APOB and by a single mRNA transcript larger than 16 kb. ApoB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a trans-acting tissue-specific splicing gene that determines which isoform is ultimately produced.^{[citation needed]} Alternatively, there is some evidence that a cis-acting element several thousand bp upstream determines which isoform is produced.^{[citation needed]}
As a result of the RNA editing, ApoB48 and ApoB100 share a common N-terminal sequence, but ApoB48 lacks ApoB100's C-terminal LDL receptor binding region. In fact, ApoB48 is so called because it constitutes 48% of the sequence for ApoB100.
ApoB 48 is a unique protein to chylomicrons from the small intestine. After most of the lipids in the chylomicron have been absorbed, ApoB48 returns to the liver as part of the chylomicron remnant, where it is endocytosed and degraded."

Regulation

The expression of APOB is regulated by cis-regulatory elements in the APOB 5' UTR and 3' UTR.^[22]

RNA editing*

The mRNA of this protein is subject to Cytidine to Uridine (C to U) site specific RNA editing. ApoB100 and ApoB48 are encoded by the same gene, however the differences in the translated proteins is not due to alternative splicing* but is due to the tissue specific RNA editing event*. ApoB mRNA editing was the first example of editing observed in vertebrates.*^[23] Editing of ApoB mRNA occurs in all placental mammals.^[24] Editing occurs post transcriptionally as the nascent polynucleotides do not contain edited nucleosides.^[25]

Type

C to U editing* of ApoB mRNA requires an editing complex or holoenzyme (editosome) consisting of the C to U-editing enzyme Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (ApoBEC-1) as well as other auxiliary factors. ApoBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.^[26][1]It is a member of the cytidine deaminase family. ApoBEC-1 alone is not sufficient for the editing of ApoB mRNA ^[27] and requires at least one of these auxiliary factors, APOBEC1 complementation factor (A1CF)^[28] for editing to occur. A1CF contains 3 non identical repeats. It acts as the RNA binding subunit and directs ApoBEC-1 to the ApoB mRNA downstream of the edited cytidine.^[29] Other auxiliary factors are known to be part of the holoenzyme. Some of these proteins have been identified. these are CUG binding protein 2 (CUGBP2),^[30] SYNCRIP (glycine-arginine-tyrosine-rich RNA binding protein, GRY-RBP),^[31] heterogenous nuclear ribonucleoprotein (hnRNP)-C1,^[32] ApoBEC-1 binding protein (ABBP)1, ABBP2,^[33] KH-type splicing regulatory binding protein (KSRP), Bcl-2-associated anthogene 4 (BAG4),^[34] and auxiliary factor (AUX)240.^[35] All these proteins have been identified using detection assays and have all been demonstrated to interact with either ApoBEC-1, A1CF, or ApoB RNA. The function of these auxiliary proteins in the editing complex are unknown.

Neurofibromiini-1  

 As well as editing ApoB mRNA, the ApoBEC-1 editsome also edits the mRNA of NF1. mRNA editing of ApoB mRNA is the best defined example of this type of C to U RNA editing in humans.
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Clinical significance

Mutations in NF1 are primarily associated with neurofibromatosis type 1 (NF1, also known as von Recklinghausen syndrome).^[5] NF1 is the most common single gene disorder in humans, occurring in about 1 in 2500-3000 births worldwide.^[19] NF1 is an autosomal dominant disorder, but approximately half of NF1 cases arise from de novo mutations. NF1 has high phenotypic variability, with members of the same family with the same mutation displaying different symptoms and symptom intensities.^[20][21] Café-au-lait spots are the most common sign of NF1, but other symptoms include lisch nodules, cutaneous neurofibromas, plexiform neurofibromas, skeletal defects, and optic nerve gliomas.^[22]
In addition to neurofibromatosis type I, mutations in NF1 can also lead to juvenile myelomonocytic leukemia, Watson syndrome,^[23] and breast cancer.^[24]