nanonug
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This is going to get a little technical so bear with me, please.
While trying to understand the biochemistry behind ketogenesis diets, I stumbled upon a condition known as Carnitine Palmitoyltransferase II Deficiency. It is associated with genetic variations in the CPT2 gene. I decided to check my CPT2 gene on ENLIS, from 23andMe data, and found several variations, all of them homozygous.
Two of the variations found were associated with protein coding and the rest are introns for which absolutely no information is available. The two protein coding are rs1799821 and rs1799822. The latter one has a minor allele frequency of ~16% and is considered benign/likely benign. The first one, on the other hand, has a "risk factor" label attached although with an allele frequency of ~48%. Homozygosity has certainly lower frequency but I don't know how much.
Focusing on rs1799821 (CPT2 V368I) homozygous mutation ("bad" allele is "A"), I found an interesting paper entitled "Abbreviated Half-Lives and Impaired Fuel Utilization in Carnitine Palmitoyltransferase II Variant Fibroblasts." In this paper, one may read the following:
In essence, being homozygous for CPT2 V368I (rs1799821) leads to decreased membrane potential. This membrane potential (literally a difference in voltage) is fundamental for the creation of ATP from ADP and inorganic phosphate. Less membrane potential leads to lower synthesis of ATP from ADP. This is even worse if one runs a fever.
While trying to understand the biochemistry behind ketogenesis diets, I stumbled upon a condition known as Carnitine Palmitoyltransferase II Deficiency. It is associated with genetic variations in the CPT2 gene. I decided to check my CPT2 gene on ENLIS, from 23andMe data, and found several variations, all of them homozygous.
Two of the variations found were associated with protein coding and the rest are introns for which absolutely no information is available. The two protein coding are rs1799821 and rs1799822. The latter one has a minor allele frequency of ~16% and is considered benign/likely benign. The first one, on the other hand, has a "risk factor" label attached although with an allele frequency of ~48%. Homozygosity has certainly lower frequency but I don't know how much.
Focusing on rs1799821 (CPT2 V368I) homozygous mutation ("bad" allele is "A"), I found an interesting paper entitled "Abbreviated Half-Lives and Impaired Fuel Utilization in Carnitine Palmitoyltransferase II Variant Fibroblasts." In this paper, one may read the following:
Reduction of mitochondrial membrane potential
We assessed the mitochondrial membrane potential (ΔΨm) using the cationic lipophilic probe JC-1. Normal mitochondria with a high ΔΨm appear red following aggregation of JC-1, which emits red fluorescence at ~590 nm. Following mitochondrial depolarization with a low ΔΨm, the JC-1 dye remains in its monomeric form, thereby emitting relatively more green (~525 nm) fluorescence [32]. We observed an increase of green fluorescence and a reduction of red fluorescence in the mitochondria of fibroblasts from patients with p.V368I (homozygous) and p.F352C (heterozygous) + p.V368I (homozygous) variants compared with mitochondria from control fibroblasts at both 37°C (Fig. 4A, B, C) and 41°C (Fig. 4D, E, F). Mitochondrial depolarization is a marker of mitochondrial dysfunction and precedes ATP depletion, so the data indicate a relatively low ΔΨm of patient fibroblasts at 37°C and an enhanced decrease in ΔΨm under heat-stress conditions at 41°C.
We assessed the mitochondrial membrane potential (ΔΨm) using the cationic lipophilic probe JC-1. Normal mitochondria with a high ΔΨm appear red following aggregation of JC-1, which emits red fluorescence at ~590 nm. Following mitochondrial depolarization with a low ΔΨm, the JC-1 dye remains in its monomeric form, thereby emitting relatively more green (~525 nm) fluorescence [32]. We observed an increase of green fluorescence and a reduction of red fluorescence in the mitochondria of fibroblasts from patients with p.V368I (homozygous) and p.F352C (heterozygous) + p.V368I (homozygous) variants compared with mitochondria from control fibroblasts at both 37°C (Fig. 4A, B, C) and 41°C (Fig. 4D, E, F). Mitochondrial depolarization is a marker of mitochondrial dysfunction and precedes ATP depletion, so the data indicate a relatively low ΔΨm of patient fibroblasts at 37°C and an enhanced decrease in ΔΨm under heat-stress conditions at 41°C.
In essence, being homozygous for CPT2 V368I (rs1799821) leads to decreased membrane potential. This membrane potential (literally a difference in voltage) is fundamental for the creation of ATP from ADP and inorganic phosphate. Less membrane potential leads to lower synthesis of ATP from ADP. This is even worse if one runs a fever.