Flashcards in Biochemistry Final: Exam #3 Review Deck (157)
What are the three sources of glutamate?
1) Diet (major)
2) Transamination of a-KG
3) Deamination of Glutamine
Amino acid + a-KG--> Glutamate + a-ketoacid
- Amine group from amino acid is carried by B6(pyridoxal 5'-phosphate) to a-KG & swapped for carboxyl group
- Makes Glutamate & corresponding a-Ketoacid
Deamination of Glutamine
Glutamine--> Glutamate, via the enzyme "Glutaminase"
Why do we make glutamine?
Glutamine production in peripheral tissues in an important mechanism of ammonium ion removal
How do we make glutamine?
Glutamate--> Glutamine, via the enzyme "Glutamine Synthetase"
- Ammonium ion required (removes toxic substance too!)
- ATP hydrolyzed to ADP + Pi
Where does this glutamine go?
Enters the bloodstream and is absorbed by the:
Here, the amide group is hydrolyzed by Glutaminase (Glutamine--> Glutamate), generating Glutamate & NH4+
What do the kidenys and liver do with ammonium ion (NH4) generated by the glutaminase reaction i.e. deamination of glutamate?
- Kidneys excrete NH4 directly
- Liver channels NH4 into the urea cycle
(Gut, NH4 serves as an important nutrient)
- Active form of pyridoxal phosphate
- Vitamin B6
- Cofactor that is required for aminotransferase reactions
Alanine + a-KG --> Pyruvate + Glutamate
Pyruvate + Glutamate--> a-KG + Alanine
- Alanine Aminotransferase (ALT)
- Requires Vitamin B6 (PLP)
- Connects muscle & liver metabolism
- Found primarily in the liver
- Muscle glycolysis produces pyruvate
- ALT converts pyruvate into alanine that is released into the blood
- Blood carries alanine to the liver
- In liver, ALT converts alanine back into pyruvate
- Pyruvate is used for gluconeogenesis
1) Oxaloacetate + Glutamate --> a-KG + Aspartate
2) Aspartate + ATP + Glutamine--> Asparagine, via the enzyme "Asparagine Synthetase"
Clinical Significance of ALT vs. AST
Serum elevation of ALT is more specific for liver damage
Folate & THF
- Tetrahydrofolate (THF) Serves as an acceptor of 1-carbon groups (methylene)
- Derived from the vitamin, Folate
Most oxidized form of THF
Most reduced from of THF
- N5-methyl THF
- Is NOT readily oxidized back to N10-formyl THF
- Thus, accumulates in the body
Which amino acid is the main donor of 1 carbon groups?
Serine Hydroxymethyl transferase
Serine + THF--> Glycine + N5, N10-methylene THF + H20
- Requires oxygen, NADH, & the reduced cofactor tetrahydrobiopterin (THBtn) to oxidize the aromatic ring of phenylalanine
Dihydrobiopterin (DHBtn, oxidized) -->Tetrahydrobiopterin (THBtn, reduced)
- Most common inborn error of metabolism
- Accumulation of phenylalanine that causes: severe intellectual disability, recurrent seizures, hypopigmentation, & eczematous skin rashes
- Caused by defect in phenylalanine hydroxylase OR DHBtn Reductase
- Must avoid nutrisweet/ aspartame
The overall rate of amino acid degradation is influenced by the activity of which enzyme? What inhibits this enzyme & what activates this enzyme?
Mitochondrial Glutamate Dehydrogenase
- Inhibited, high energy: GTP, ATP, NADH
- Activated, low energy: GDP, ADP, NAD+
Mitochondrial Glutamate Dehydrogenase
Glutamate + NAD+ + H20 --> a-KG + NADH + NH4+
Which amino acids can be converted into pyruvate? And what is pyruvate eventually used to make?
Glycine, through several steps, can eventually be converted into pyruvate. How is glycine also related to the formation of kidney stones?
Glycine--> Serine --> Pyruvate = one possible path
Glycine--> Glyoxalate--> Oxalate= second possible path
- Oxalate is a metabolic end product that is excreted in the urine
- Oxalate also has a high affinity for Ca++, and can precipitate as kidney stones
Besides via pyruvate, two other amino acids can be shunted to make OAA. Which?
Asparagine--> Asparate, via enzyme "asparaginase"
Aspartate--> OAA, via AST
Which amino acid can be used to make a-KG?
Glutamine--> Glutamate, via enzyme "Glutaminase"
Glutamate--> a-KG, via Aminotransferases & Glutamate Dehydrogenase
Therefore, amino acids that can make glutamate, can also be used to make a-KG
Which amino acids can make glutamate?
- Nonketotic hyperglycemia that presents soon after birth with symptoms of: lethargy, lack of muscle tone, & muscle twitching
- Caused by defects in glycine cleavage system
What amino acids can make propoionyl-CoA?