diabetes

[velamj]

Hello. I had a quick question related to diabetes. The question states: Which of the following metabolic intermediates would be expected to be decreased in a diabetic compared to a non-diabetic.
a. Acetyl-CoA
B. Lactic Acid
c.NADH
D.Ketone bodies

so ACCORDING to my class ICC (Princeton Rev. Bio passage 15 #4) the answer is Lactic Acid.... I know lactic acid pertains to anaerobic respiration and I know diabetics have high serum glucose levels due to the fact that they either lack insulin receptors (DM2 i think) or lack Beta cells on the pancrease ( islets of langerhans) which produce insulin (Dm1). Im trying to make the connection between high blood glucose levels and an inability to produce a lactic acid intermediate ...how are high blood glucose levels and anaerobic resp related? Maybe I accidently put the wrong answer but i really doubt it. Would greatly appreciate some help.

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[RogueUnicorn]

diabetes is starvation in plenty... cells can't bring in the sugar from the bloodstream either from lack of insulin or from insulin resistance. thus, any glycolytic byproduct would be reduced while beta oxidation and amino acid catabolism byproducts would increase. lactic acid can only be formed through glycolysis, so B is the answer. the rest can be generated (quite well) via beta oxidation

 

[velamj]

ok i think i get it now...but what exactly is beta oxidation and how can it restore NADH? whats was confusing i guess is the the fact that in addition to pyruvate, NADH and some atp are also produced in glycolysis so i figured they would be decreased as well in this scenario... can u explain it in some detail?

 

[velamj]

I didnt realize that NADH can be restored through other means...ie beta oxidation

 

[Charles_Carmichael]

ok i think i get it now...but what exactly is beta oxidation and how can it restore NADH? whats was confusing i guess is the the fact that in addition to pyruvate, NADH and some atp are also produced in glycolysis so i figured they would be decreased as well in this scenario... can u explain it in some detail?

Beta oxidation is where fatty acids are converted to acetyl-CoA (and produce NADPH as a byproduct) and are put into the TCA cycle. As a side-note (if I remember correctly), NADH itself is not replaced by beta oxidation; rather beta oxidation generates NADPH, which is preferably used in anabolic processes rather than catabolic ones.

Lactic acid would increase when there's a ton of glycolysis going on because you want to restore the NAD+ to keep glycolysis going. But in diabetes, there's a decrease in glycolysis because the body thinks it doesn't have enough glucose (so you want to spare as much glucose as possible and thus, you won't be breaking it down). So what actually happens is that there's an increase in gluconeogenesis (making of new glucose) while glycolysis is decreased. Since there's a decrease in glycolysis, of which a byproduct is NADH, there's no need to regenerate NAD+. So there's no need for shunting pyruvate towards the lactic acid pathway. Thus, there's no increase in lactic acid produced. Do you understand?

For answering this question, I think it's best to just focus on glucose metabolism rather than thinking about fatty acid metabolism and making things more complicated.

Hope this helps.

 

[loveoforganic]

You do get a couple reducing equivalents out of each B-oxidation cycle directly. On top of that though, you get acetyl-CoA, which is going to net you more.