Step I Biochemistry question

[Phloston]

P. 100 of FA says "overproduction of malate (with alcohol intoxication) increases NADPH and thus fatty acid synthesis."

1) I'm guessing since the increased NADH/NAD+ ratio shunts OAA --> malate, NADPH increases because malate dehydrogenase attempts to shunt malate back to pyruvate via NADP+ --> NADPH. Is that correct?

2) Why would FA synthesis be increased in relation to NADPH and malate?

 

[ZGX]

FA 2012 errata
FA 2012 has a lot of errors

http://firstaidteam.com/updates-and-corrections

 

[Phloston]

That errata-correction doesn't make sense though because that would mean FA now says "overproduction of malate increases NADH," when in fact it's the increased NADH that increases malate.

Increased NADPH due to malate excess would make sense because:

"Malate dehydrogenase is an enzyme that catalyzes the chemical reaction: malate + NADP+ <--> pyruvate + CO2 + NADPH" - Wiki

I'm not so sure FA should have made that correction. Btw, doesn't their errata have an errata?

 

[ZGX]

Ethanol consumption in excess increases NADH/NAD ratio.

Excess NADH pushes
(1) Pyruvate --> Lactate. Consume NADH, release NAD
(2) OAA --> Malate. Consume NADH, release NAD
Both substrates are pre-cursors for Gluconeogesis, which is now impaired.

In Fatty Acid Synthesis
Malate --> 2 Pyruvate's are formed
In that process NADP+ is consumed, releasing NADPH which drives
Acetyl CoA --> Palmitate

To reverse the process:
NADH is also used in break down Fatty Acids. However the majority of NADH is used in other processes resulting in a now low NADH/NAD ratio. Meanwhile Fatty Acid Synthesis is still going, as opposed to it being broken down. Fatty Acid builds up (lipogenesis) results in Fatty Liver.

 

[Phloston]

FA is definitely wrong with their errata-correction. Time for another errata.

NADPH is used to get malonyl-CoA to FAs during FA synthesis. So the increased NADPH generated secondary to the malate excess, secondary to the increased NADH/NAD+ ratio seen in EtOH, helps drive intra-hepatic synthesis of FAs.

 

[Chirurg]

FA is definitely wrong with their errata-correction. Time for another errata.

NADPH is used to get malonyl-CoA to FAs during FA synthesis. So the increased NADPH generated secondary to the malate excess, secondary to the increased NADH/NAD+ ratio seen in EtOH, helps drive intra-hepatic synthesis of FAs.

agree with that.