ALT/AST - quick question

[Phloston]

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AST serum levels indicate mitochondrial damage, since AST is normally used in the mitochondria for the aspartate-malate shuttle.

This also explains the concentrations of B6 in the mitochondria (e.g. haeme synthesis).

Is ALT therefore also mitochondrial (given this reaction also involves glutamate <--> alpha-ketoglutarate equilibrium)?

I'm just trying to conclude what the presence of ALT actually means in terms of molecular/organellar damage.

Cheers,

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And if anyone knows anything more specifically about GGT and ALP, I'd appreciate it if you'd share.

 

[frankyazz]

From my understanding, ALT is present in the cytosol, so it is a specific enzyme of liver cell necrosis.

 

[MrBeauregard]

AST serum levels indicate mitochondrial damage, since AST is normally used in the mitochondria for the aspartate-malate shuttle.

This also explains the concentrations of B6 in the mitochondria (e.g. haeme synthesis).

Is ALT therefore also mitochondrial (given this reaction also involves glutamate <--> alpha-ketoglutarate equilibrium)?

I'm just trying to conclude what the presence of ALT actually means in terms of molecular/organellar damage.

Cheers,

----

And if anyone knows anything more specifically about GGT and ALP, I'd appreciate it if you'd share.

Yep, AST is mitochondrial and ALT is cytosolic. AST is elevated in alcohol-induced injury since alcohol is a mitochondrial toxin and specifically damages them. ALT is elevated hepatitis because of cellular necrosis.

And just one question: why do you spell 'heme' as 'haeme'? Is it just to be different or do you also spell 'color' as 'colour' and such? Just wondering.

 

[doopdidoop]

And just one question: why do you spell 'heme' as 'haeme'? Is it just to be different or do you also spell 'color' as 'colour' and such? Just wondering.

he's Australian! 🙂

 

[MrBeauregard]

Yeah, but for some reason I didn't think he was native to Australia. I realize Australians use the grapheme ae from Latin/Old English. Not calling him out or anything.

 

[Phloston]

Yep, AST is mitochondrial and ALT is cytosolic. AST is elevated in alcohol-induced injury since alcohol is a mitochondrial toxin and specifically damages them. ALT is elevated hepatitis because of cellular necrosis.

And just one question: why do you spell 'heme' as 'haeme'? Is it just to be different or do you also spell 'color' as 'colour' and such? Just wondering.

Cool. So AST is mitochondrial and ALT is cytosolic. However, I'm unclear on one point you've just provided.

Ethanol dehydrogenase is SER (and MEOS is peroxisomal), whereas acetaldehyde dehydrogenase is mitochondrial. Therefore, in EtOH poisoning, I'd think the raised ALT would be due to the ethanol and the AST would be due to the acetalehyde. Is that correct?

he's Australian! 🙂

Yeah, but for some reason I didn't think he was native to Australia. I realize Australians use the grapheme ae from Latin/Old English. Not calling him out or anything.

I'm from New York. I split my undergrad between Boston and Sydney. I had done infective endocarditis research between a couple hospitals in New South Wales back in 2007 and took writing courses at University of Sydney. It was the most exciting time of my life and I learned a lot, so I decided to come back for the rest of my 20s (i.e. seven more years), knowing that I'd have to work hard to get back to the US, but that it would ultimately be worth it.

Everything is ae and oe over here. It's TOE, not TEE; it's GORD, not GERD; it's haeme, not heme. Yeah..

 

[MrBeauregard]

Ethanol dehydrogenase is SER (and MEOS is peroxisomal), whereas acetaldehyde dehydrogenase is mitochondrial. Therefore, in EtOH poisoning, I'd think the raised ALT would be due to the ethanol and the AST would be due to the acetalehyde. Is that correct?

That's a good question, and one that I am not educated enough to answer. I just remember from Goljan RR and from his audio that he states "alcohol is a mitochondrial poison" and so AST is elevated more than ALT in alcoholic liver disease. Your reasoning makes sense, though.

I'm from New York. I split my undergrad between Boston and Sydney. I had done infective endocarditis research between a couple hospitals in New South Wales back in 2007 and took writing courses at University of Sydney. It was the most exciting time of my life and I learned a lot, so I decided to come back for the rest of my 20s (i.e. seven more years), knowing that I'd have to work hard to get back to the US, but that it would ultimately be worth it.

Everything is ae and oe over here. It's TOE, not TEE; it's GORD, not GERD; it's haeme, not heme. Yeah..

Interesting. Where in Boston (I have an idea)?

And you'll make it back to the US.

 

[Phloston]

That's a good question, and one that I am not educated enough to answer. I just remember from Goljan RR and from his audio that he states "alcohol is a mitochondrial poison" and so AST is elevated more than ALT in alcoholic liver disease. Your reasoning makes sense, though.



Interesting. Where in Boston (I have an idea)?

And you'll make it back to the US.

I had been itinerant for the most part. I actually lived in Kenmore Square when the Red Sox won the World Series, so the Boston riots (and, yes, the cops do come out on horseback), were in my bedroom. I want gen surg residency in Boston.

 

[MrBeauregard]

I want gen surg residency in Boston.

Haha, me too. But not in Boston (they'd favor you over me, for sure).

 

[ijn]

Do you really need a 270 to do general surgery in Boston?

 

[doopdidoop]

I'm from New York.

whoops! my bad!

Do you really need a 270 to do general surgery in Boston?

certainly can't hurt!

 

[Phloston]

Do you really need a 270 to do general surgery in Boston?

My relative, who's at HMS, and I were talking tonight (mostly about the USMLE), and he was largely just reiterating the fact that it's not just the USMLE, but also research, that is a tremendous consideration over there (which I already knew).

Once again, he said he's only heard stories of a few people who've broken 270, and his class average was 238 (he just started MS4 now). The impression he's given me a couple times is that scores >240 are a big deal. However I'm also playing an IMG card.

He said if there's any shot at a residency there, the candidate needs to be research-willing/promising.

 

[ijn]

The national average is 225. Harvard's average is only 238? That's kind of unimpressive considering they have the pick of the top students in the country.

 

[Phloston]

The national average is 225. Harvard's average is only 238? That's kind of unimpressive considering they have the pick of the top students in the country.

I had that cross my mind too, but knowing him, it occurred to me that HMSers are generally the type who have always coveted doing well in the classroom, and we're all well aware at this point that many top USMLE scorers (including Pollux) tend to be mid-ranked students who study a lot at home, who also don't obsess over SoM requirements.

My relative hadn't told me his exact score, but I can guess that he got 235-245, just based on numerous things he's said (i.e. acting like it's a super big deal if someone gets 240s and also sounding frustrated by not having had a lot of time to prep). I am aware that he got a 2400 on the SATs and 4.0s at Harvard undergrad; the latter emphasizes the point in the first paragraph and the former the fact that the USMLE is very much prep-, rather than intuition-based, when it comes to scores >245.