LSM2101 Part II Lecture 2 Ammonia Production and Detoxification

Conversion of AA to Keto Acids

• Oxidative Deamination
• L-AA Oxidase + FMN + Catalase

• L-Glutamate Dehydrogenase + NAD+

• Transamination
• Mechanism: 
• Transfer of amine group from AA to PLP: 1. Transamination 2. Tauromerization 3. Hydrolysis
• Transfer of amine group from PLP to Keto-Acid: reverse of above

• General: 

• Aspartate-Aminotransferase (Glutamate-oxaloacetate transaminase)

• Alanine-Aminotransferase (Glutamate-pyruvate Transaminase)

• AST & AST: indication of damaged cells if found in blood serum.
• Trasndeamination: Transamination + Oxidative Deamination

• Importance:
• Funneling to glutamate for conversion to ammonia.
• Synthesis of non-essential amino acids.
• Non-Oxidative Deamination
• Ammonia Lyases

• Specific Deaminases:
• Serine dehydratase (L-serine hydrolase)

• Threonine dehydratase

• Cysteine desulfhydrase

Excretion of Ammonia

• AA -> Glu (1 eq NH3) -> Gln (2 eq NH3): happens in everywhere, transported to kidney or liver.
• Gln (2 eq NH3) -> Glu (1 eq NH3) + NH4+: only happens in kidney and liver.
• Ion-trapping mechanism: since NH4+ can't cross cell's membrane, ammonium ions in kidney lumen cannot enter kidney cells.

LSM2101 Part II Lecture 3 The Urea Cycle and Disorders

Lecture 3: Urea Cycle / Ornithine Cycle

• Urea: NH2-CO-NH2 (first N is from Asp, the other one is from ammonia, C is from CO2)
• Carbamoyl Phosphate synthesis is a rate-limiting step

•  Regulation:  Carbamoyl Phosphate Synthetase
• CP I: ammonia dependent, N-acetylglutamate -> activator, mitochondrial
• CP II: Amide-N of glutamine, independent from  N-ace glu, cytoplasmic
• N-acetylglutamate: from Glu + Arg using Acetylglutamate Synthase (N-acteyl Transferase)

• Kreb's Bicycle

 

•  Metabolic Disorder - Hyperammonemia (Defects in enzymes)
• Hyperammonemia Type I: Carbamoyl Phosphate Synthetase I
• Hyperammonemia Type II: Ornithine Transcarbamoylase
• Citrullinemia: Argininosuccinate Synthetase
• Argininosuccinic aciduria/acidemia: Argininosuccinate lyase/Argininosuccinase
• Argininemia: Arginase

• Nitrogen Disposal
• Ureotelic-Urea: Mammals
• Ammonotelic-Ammonia: Fishes
• Uricotelic-Ric Acid: Birds

LSM2101 Part II Lecture 1 Overview

So, Part 2 is about Amino Acid Metabolism.
I skipped the first part since I've rarely attended the lectures. :D But the first part is about carbohydrate metabolism. Maybe I'll post the summary later.


Okay then...
Let's go on to the first lecture of second part of LSM2101:  Overview


1. Why do we need amino acids?
protein synthesis, energy & gluconeogenic substrates, neurotransmitter, hormones, heme & nucleotide biosynthesis.


2. Composition of body
50% dry matter = protein, 1-2% dry matter = free amino acids, no large reservoir of amino acids.


3. Where does body gets amino acids?
dietary proteins (exogenous), breakdown of body's proteins (endogenous), biosynthesis.


4. Dietary Proteins' Fate

• Intake:
• minimum daily req = 30 g for 70kg person
• Digestion:

• Absorption & Transportation:
• Inborn Errors: Aminoacidurias
• Cystinuria: failure to absorp CystineOrnithineArginineLysine -> Cystine Kidney Stones
• Hartnup's Disease: failure to absorp Trp, Phe, neutral AA -> Cerebellar ataxia (coordination of involuntary movement), Pellagra-like symptoms.

5. Nitrogen Balance

• Balance: Intake = Output
• Positive N Balance: Intake > Output (Growth, Pregnancy, Refeeding)
• Negative N Balance: Intake < Output (Starvation, Senescence, Metabolic Stress)