AMACR geenin koodaama rasemaasi vaikuttaa aktivoituihin C27 sappihappoihin ,niiden välituotteeseen, arylpropionihappoon, ibuprofeeniin, eikä vain aktivoituun pristanyyliin !

 Olisikohan Refsum-dieetin periaatteista  tässäkin   entsyymin vaikutusalan haarassa jotin merkitystä etuja? Metabolisen taakan helpottamista?

Functional Descriptions for AMACR proteins

Uniprot Function
for Q9UHK6

• Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters
• Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs. 3 Publications

GenAtlas Summary
for AMACR

• alpha-methylacyl-CoA racemase,expressed in liver,peroxisomal,converting pristanoyl-CoA and C27 beta acyl-CoA to their (5) stereoisomers,essential step for the formation of cholic acid by the normal peroxisomal pathway

GO Molecular Functions for AMACR

AMACR alpha-methylacyl-CoA racemase [ Homo sapiens (human) ]

Gene ID: 23600, updated on 13-Oct-2026

Download Datasets

Summary

Official Symbol

AMACRprovided by HGNC

Official Full Name

alpha-methylacyl-CoA racemaseprovided by HGNC

Primary source

HGNC:HGNC:451

See related

Ensembl:ENSG00000242110 MIM:604489; AllianceGenome:HGNC:451

Gene type

protein coding

RefSeq status

REVIEWED

Organism

Homo sapiens

Lineage

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo

Also known as

RM; RACE; CBAS4; P504S; AMACRD

Summary

This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]

Expression

Broad expression in kidney (RPKM 38.3), liver (RPKM 31.1) and 22 other tissues See more

Orthologs

all

Try the new Gene page

ORP5 tekee yhteistyötä NPC1 proteiinin kanssa

https://previous.genecards.org/cgi-bin/carddisp.pl?gene=OSBPL5

• GeneCards Symbol: OSBPL5 2 
• Oxysterol Binding Protein Like 5 2 3 5
• OBPH1 2 3 4 5
• ORP5 2 3 4 5
• KIAA1534 2 4 5
• Oxysterol-Binding Protein-Related Protein 5 3 4
• Oxysterol-Binding Protein Homolog 1 3 4

• OSBP-Related Protein 5 3 4
• ORP-5 3 4
• Oxysterol Binding Protein Homologue 1 2
• Oxysterol-Binding Protein Homologue 1 3
• Oxysterol Binding Protein-Like 5 2
• EC 2.7.7.6 47
• EC 1.2.1 47

• This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

GeneCards Summary for OSBPL5 Gene

OSBPL5 (Oxysterol Binding Protein Like 5) is a Protein Coding gene. Diseases associated with OSBPL5 include Lenz-Majewski Hyperostotic Dwarfism and Peeling Skin Syndrome. Among its related pathways are Glycerophospholipid biosynthesis and Metabolism. Gene Ontology (GO) annotations related to this gene include cholesterol binding and oxysterol binding. An important paralog of this gene is OSBPL8.

UniProtKB/Swiss-Prot Summary for OSBPL5 Gene

Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:23934110, 26206935). May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes (PubMed:21220512). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). ( OSBL5_HUMAN,Q9H0X9 )

GLYMFAATTINEN SYSTEEMI. Perustietoa.

 https://pmc.ncbi.nlm.nih.gov/articles/PMC4636982/

. Author manuscript; available in PMC: 2016 Dec 1.

Published in final edited form as: Neurochem Res. 2015 May 7;40(12):2583–2599. doi: 10.1007/s11064-015-1581-6

The Glymphatic System – A Beginner's Guide

Nadia Aalling Jessen ^1,1, Anne Sofie Finmann Munk ^1,1, Iben Lundgaard ^1,1, Maiken Nedergaard ¹

Kolesterolin kierrätys hermokudoksessa aivoissa. GLYMFAATTINEN SYSTEEMI.

 https://pubmed.ncbi.nlm.nih.gov/?term=recirculation+of+cholesterol+in+brain

https://pubmed.ncbi.nlm.nih.gov/28188218/

 The glymphatic system is a brain-wide network of channels surrounding brain blood vessels that allows CSF to exchange with interstitial fluid, clearing away cellular wastes such as amyloid β. We observed that, in mice, microinfarcts impaired global glymphatic function and solutes from the CSF became trapped in tissue associated with microinfarcts. These data suggest that small, disperse ischemic lesions can impair glymphatic function across the brain and trapping of solutes in these lesions may promote protein aggregation and neuroinflammation and eventually lead to neurodegeneration, especially in the aging brain.

The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid β and tau.

...findings indicate that glymphatic function is focally disrupted around microinfarcts and that the aging brain is more vulnerable to this disruption than the young brain. These observations suggest that microlesions may trap proteins and other interstitial solutes within the brain parenchyma, increasing the risk of amyloid plaque formation

https://pubmed.ncbi.nlm.nih.gov/26118970/

ACAT1 , ACAT2 kolesteroli-asyylitransferaasit, kolesteroliestereiden muodostajaentsyymit

. Review Article Acyl coenzyme A : cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis Rudel, Lawrence L.; Lee, Richard G.; Cockman, Terri L. Author Information Current Opinion in Lipidology 12(2):p 121-127, April 2001. 

 Abstract Two enzymes are responsible for cholesterol ester formation in tissues, acyl coenzyme A : cholesterol acyltransferase types 1 and 2 (ACAT1 and ACAT2). The available evidence suggests different cell locations, membrane orientations, and metabolic functions for each enzyme. ACAT1 and ACAT2 gene disruption experiments in mice have shown complementary results, with ACAT1 being responsible for cholesterol homeostasis in the brain, skin, adrenal, and macrophages. ACAT1 −/− mice have less atherosclerosis than their ACAT1 +/+ counterparts, presumably because of the decreased ACAT activity in the macrophages.

 By contrast, ACAT2 −/− mice have limited cholesterol absorption in the intestine, and decreased cholesterol ester content in the liver and plasma lipoproteins. Almost no cholesterol esterification was found when liver and intestinal microsomes from ACAT2 −/− mice were assayed.

 Studies in non-human primates have shown the presence of ACAT1 primarily in the Kupffer cells of the liver, in non-mucosal cell types in the intestine, and in kidney and adrenal cortical cells, whereas ACAT2 is present only in hepatocytes and in intestinal mucosal cells. 

The membrane topology for ACAT1 and ACAT2 is also apparently different, with ACAT1 having a serine essential for activity on the cytoplasmic side of the endoplasmic reticulum membrane, whereas the analogous serine is present on the lumenal side of the endoplasmic reticulum for ACAT2. 

Taken together, the data suggest that cholesterol ester formation by ACAT1 supports separate functions compared with cholesterol esterification by ACAT2. The latter enzyme appears to be responsible for cholesterol ester formation and secretion in lipoproteins, whereas ACAT1 appears to function to maintain appropriate cholesterol availability in cell membranes.

Aivot ja kolesteroli

 https://pmc.ncbi.nlm.nih.gov/articles/PMC3484857/

Although the brain makes up only 2–5% of body mass, approximately 25% of total body cholesterol resides in the brain (Dietschy and Turley, 2001). Thus, the brain is highly enriched in cholesterol compared with other mammalian tissues: whereas the cholesterol concentration in most animal tissues is ∼2 mg/g tissue, the cholesterol concentration in the CNS is 15–20 mg/g tissue (Dietschy and Turley, 2004).

 The majority (70–90%) of cholesterol in the CNS is in the myelin that surrounds axons and facilitates the transmission of electrical signals. 

Consequently, cholesterol synthesis in the brain is highest in oligodendrocytes during active myelination and decreases by ∼90% in adults after myelination has been completed (Dietschy and Turley, 2004; Quan et al., 2003).

 Nevertheless, cholesterol synthesis continues at a low rate in the mature brain, particularly in astrocytes; in the adult brain, the rate of cholesterol biosynthesis is higher in astrocytes than in neurons (Nieweg et al., 2009).

Transport

The brain operates its own lipoprotein transport system, independent of that in the peripheral circulation (Fig. 2). 

Astrocytes produce cholesterol and apolipoprotein E (APOE) that, together with phospholipids, generate lipoproteins that are similar in size to plasma high-density lipoproteins (Boyles et al., 1985). 

The secreted APOE acquires cholesterol and phospholipids via the efflux of cellular lipid in a process mediated by one or more of the ATP-binding cassette (ABC) transporters such as ABCA1, ABCG1 and/or ABCG4 

The uptake of these lipoproteins by neurons is mediated by receptors of the low-density lipoprotein (LDL) receptor family, such as the LDL receptor, LDL-receptor-related protein (LRP) and APOE receptor 2 (APOER2), that are expressed in neurons and can endocytose the astrocyte-derived APOE-containing lipoprotein particles (Boyles et al., 1989; Herz, 2001b; Posse de Chaves et al., 2000) (Fig. 2). 

In this manner, cholesterol is shuttled from astrocytes to neurons (Mauch et al., 2001; Michikawa et al., 2000; Vance and Hayashi, 2010). 

The interaction between APOE-containing lipoproteins and these neuronal receptors seems to be crucial for normal neuronal function:

 the APOE-containing lipoproteins stimulate synaptogenesis (Mauch et al., 2001), enhance axonal growth (Hayashi et al., 2004) and
 prevent neuron death (Hayashi et al., 2009; Hayashi et al., 2007)

 Moreover, a role for APOE in nerve repair has been indicated, because APOE synthesis in glial cells increases by up to 150-fold after a nerve injury (Ignatius et al., 1986). APOE therefore seems to be a key player in regulating cholesterol homeostasis and distribution among cells of the brain.

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APOE-containing lipoproteins transport cholesterol from astrocytes to neurons. Glial cells, primarily astrocytes, but also microglia, secrete APOE, which acquires cholesterol and phospholipids, thereby forming APOE-containing lipoproteins. These are delivered to neurons where they are endocytosed via cell surface receptors (members of the LDL receptor family). Consequently, cholesterol is delivered to the neurons. Some APOE receptors also function as signaling receptors.

Cholesterol has a remarkably long half-life in the brain (4–6 months in rodents and up to 5 years in humans) (Dietschy and Turley, 2001). 

There is a low rate of cholesterol synthesis in the adult brain, and cholesterol cannot be degraded in the CNS, but a steady-state level of cholesterol is maintained in the CNS because a small fraction (0.02–0.4%) of the cholesterol pool is excreted from the brain each day (Dietschy and Turley, 2004).

 The conversion of cholesterol to 24-hydroxycholesterol (Fig. 1), by the enzyme cholesterol 24-hydroxylase (CYP46) that is expressed in a subset of neurons (but not in astrocytes) (Russell et al., 2009), represents a major mechanism by which excess cholesterol is eliminated from the brain. 

In contrast to cholesterol, 24-hydroxycholesterol can cross the blood-brain barrier, enter the peripheral circulation and be eliminated from the body in bile (Russell et al., 2009).

 Studies in CYP46-deficient mice show that at least 40% of the cholesterol that is excreted from the brain is in the form of 24-hydroxycholesterol. Interestingly, however, in CYP46-deficient mice, cholesterol does not accumulate because cholesterol synthesis is reduced by ∼40% as a compensatory mechanism (Russell et al., 2009).

APOB48 ja APOB-100 apolipoproteiinit

 

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=APOB&keywords=Apolipoprotein,B

ApoB-48  tutkimuksista: ApoB-48 syntetisoituu suolessa.  ApoB-100 syntetisoituu  maksassa. 

 https://pubmed.ncbi.nlm.nih.gov/40591354/

MTTP geeni, https://www.genecards.org/cgi-bin/carddisp.pl?gene=MTTP&keywords=MTTP

MTTP (Microsomal Triglyceride Transfer Protein) is a Protein Coding gene. Diseases associated with MTTP include Abetalipoproteinemia and Abdominal Obesity-Metabolic Syndrome 1. Among its related pathways are Plasma lipoprotein assembly, remodeling, and clearance and Cholesterol metabolism. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and lipid transporter activity.  

MTP proteiini mikrosomaalinen triglyserejä erittävä proteiini  (  vaikuttaa suolistossa  ApoB48 ja  maksassa ApoB100 lipoproteiinieneritystä. 

 The microsomal triglyceride transfer protein (MTP) is essential for the secretion of apolipoprotein B (apoB)48- and apoB100-containing lipoproteins in the intestine and liver, respectively. Loss of function mutations in MTP cause abetalipoproteinemia.

 https://pubmed.ncbi.nlm.nih.gov/35931202/

KELCH-12 proteiinin osuus  poissuljettu DOI: 10.1152/ajpendo.00219.2025   KLHL12 has been reported to regulate the trafficking of large COPII vesicles from the ER to the Golgi, including VLDL secretion in the hepatoma cells. Lipid absorption in the intestine involves COPII-mediated trafficking of chylomicron in enterocytes. Our findings demonstrate that the deletion of intestinal Klhl12 does not significantly alter systemic lipid levels or body weight under different dietary challenges, suggesting that KLHL12 is not required for lipid absorption and chylomicron metabolism

https://pubmed.ncbi.nlm.nih.gov/40514653/ 

https://pubmed.ncbi.nlm.nih.gov/40514653/ 

AI

Further Research and Clinical Implications:

• Mechanisms:

  While the link between ApoB and cancer is becoming clearer, the exact mechanisms by which ApoB influences tumor growth, metastasis, and response to therapy are still being investigated. 

  Clinical Applications:

 

Further research is needed to validate ApoB as a reliable prognostic marker and to explore its potential as a therapeutic target in various cancers. 

Individualized Treatment: Understanding the role of ApoB in cancer may lead to more personalized treatment strategies, tailoring therapies based on individual ApoB levels and other relevant factors