Biochemistry Final: Exam #3 Review Flashcards
What are the three sources of glutamate?
1) Diet (major)
2) Transamination of a-KG
3) Deamination of Glutamine
Transamination
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:
- Kidneys
- Liver
- Gut
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)
PLP
- Active form of pyridoxal phosphate
- Vitamin B6
- Cofactor that is required for aminotransferase reactions
ALT
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
Glucose-Alanine Cycle
- 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
AST
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
N10-formyl 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
Serine Hydroxymethyl transferase
Serine + THF–> Glycine + N5, N10-methylene THF + H20
Phenylalanine Hydroxylase
Phenylalanine–> Tyrosine
- Requires oxygen, NADH, & the reduced cofactor tetrahydrobiopterin (THBtn) to oxidize the aromatic ring of phenylalanine
Dihydrobiopterin Reductase
Dihydrobiopterin (DHBtn, oxidized) –>Tetrahydrobiopterin (THBtn, reduced)
Phenylketonuira (PKU)
- 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
- Serine
- Cysteine
- Alanine
- OAA
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