Ammonia Metabolism Flashcards
Do we use nitrogen for energy?
No. We pee it out as the urea cyle has plenty of excess capacity
True, false - Adults have generally run at a nitrogen surpluss, while kids are balanced.
Name a case when adults run at a deficit
False - adults’ nitrogen intake is balanced with nitrogen elimination (except with hardcore bodybuilders)
Kids consume more than they eliminate; have a positive balance.
In anhorexia, adults pee more than they consume
Nitrogen balance =
How many grams of nitrogen per gram of protein?
Nitrogen in diet (g) - urinary urea nitrogen (g) - X o
X is a constant ranging from 2-4 based on how food nutrients are taken (oral vs parental). X is higher in kids.
1 gram of protein –> .16 g N
Dietary protein intake
Dietary protein is digested down to single amino acids in the gut and intestinal epithelial cells.
Once amino acids enter the blood; they are first transported to the liver.
How are amino acids taken up in the intestinal lumen?
NEED-TO-KNOW AA’s, conjugates and function
Glutamate, a-ketoglutarate - The amino group pool of the cell
Aspartate, oxaloacetate - Donates nitrogen to the urea cycle
Alanine, pyruvate - A key role in gluconeogenesis
Glutamine, glutamate - Transports nitrogen to liver for urea cycle
When cells need to breakdown proteins for energy, which ones are used?
Branch-chained AA’s are used directly by cells they’re in. AA’s like Ala are not used for E in their respective cells; rather, they are lopped off, enter the blood stream and head to the liver for gluconeogenesis.
Protein digestion and AA turnover. What promotes storage pathways?
During the fed state, dietary AA’s enter which pool? The Protein pool for storage or the AA pool for energy generation?
AA’s enter the protein pool via translation during fed states. AA’s enter the AA pool via proteolysis during fasting, but more over starved states.
If branch chain AA’s are used by muscle cells for energy during fasting states, glutamine and alanine –> liver for gluconeogenesis in liver –> glucose. What are circulating hormones that regulate this?
Glucagon, cortisol, epinephrine and norepinephrine promote mobilization of stored fuels.
In fasted state,_____ promotes protein breakdown. _______ is the main intracellular pool of amino groups; it donates N, while it’s conjugate (alpha-KG) accepts N groups to/from other AAs. What drives this?
________ and _______ can add free ammonium to “fix” it as glutamine. These reactions require energy. True/false - this is a transamination.
Is E gained from breaking another AA bond?
What 3 enzymes fix free nitrogen (NH4+/NH3)?
Glutamante dehydrogenase, glutamine synthetase and carbamoyl phosphate synthetase
Glutamate dehydrogenase
What is the function of the Urea Cycle?
Function is to convert nitrogen to urea, which can be excreted in the urine.
What two ways does nitrogen enter the urea cycle?
As free ammonium and as aspartate
What is ornithine in the Urea cycle analagous to?
Ornithine plays an analogous role as oxaloacetate in the TCA cycle.
_____ is a key allosteric regulator of the urea cycle.
ARGENINE increases synthesis of N-acetyl-glutamate (NAG) by N-acetyl-glutamate synthase. NAG acts as an allosteric activator of carbamoyl phosphate synthetase I.
It’s the substrate that contains urea. After argenase lopps off urea, ornithine is regenerated and heads back into the mitochondria to join carbamoyl phosphate to form citrulline.
What is the main regulator of the urea cycle?
The liver has a high capacity to fix nitrogen as urea. The availability of substrates is the main regulator of urea cycle flux (feed forward regulation).
How else is the urea cycle regulated?
The urea cycle is also modulated by allosteric regulation of CPS-I and transcriptional regulation of urea cycle enzymes.
What does lots of argenine in BS mean?
Lots of arginine suggests backup of urea cycle. Drug target if inherited defect in N-acetyl-glutamate synthase.
