Amino Acid Oxidation and the Production of Urea

Chapter 18

Amino Acid Oxidation, Production of Urea

– How proteins are digested in animals– How amino acids are degraded in animals

as a source of energy– How urea is made and excreted– Some genetic defects in amino acid

recycling

Key topics: To Know

The use of amino acids as fuel varies greatly by organism

• About 90% of energy needs of carnivores can be met by amino acids immediately after a meal

• Microorganisms scavenge amino acids from their environment for fuel when needed

• Only a small fraction of energy needs of herbivores are met by amino acids

• Plants do not use amino acids as a fuel source, but can degrade amino acids to form other metabolites

Metabolic Circumstances of Amino Acid Oxidation

• Leftover amino acids from normal protein turnover

• Dietary amino acids that exceed body’s protein synthesis needs

• Proteins in the body can be broken down to supply amino acids for energy when carbohydrates and fats are scarce (starvation, diabetes mellitus)

Overview

Proteosome Function

Core Proteasome

Ubiquitin Binding Sites top and bottomNature 445:618 Feb 8, 2007

5th Edition: See pages 1107-1109, Fig 27-47, -48

6th Edition: See pages 1147-1149, Fig 27-47, -48.

Ubiquitin Targeting a Cytoplasmic

Protein

Protein Amino Terminal-aa Determines Protein’s Half-life

stabilizing

M, G, A, S, T, V >20 hrs

destabilizing

I, N, Y, D, P, L, F, D, K, R 30 – 2 min

Nitrogen Delivered to Liver Cells

Nitrogen Excretion Forms

Transaminases

EOC Problem 1 a Transamination Problem.

PLP – Transaminase Cofactor

Transaminases Used in Diagnosis of Tissue Damage

Tissue damage leaks enzymes into blood

(S)GPT: glutamate-pyruvate transaminase(S)GOT: glutamate-oxaloacetate transaminase

-- indicate probable liver damage (toxins, infections)

(S)CK: creatine kinase-- heart damage heart attack, infection

S for “serum”

EOC Problem 2: Measuring transaminases in blood – coupled reactions! (to things you already know)

Glutamate Dehydrogenase

Glutamine

Synthetase

This is just one reaction: Glutamine Synthetase

Glucose-Alanine

Cycle is in Muscle Only

EOC Problem 3: Alanine and Glutamine in Blood.

Urea Cycle Overview

Amino acids come from recycling (glutamine), muscle glycolysis (alanine), and diet.

Begin in the Mitochondrion

Mechanims of the Two Nitrogen Entry Points in Urea Cycle

Relationship to Citric Acid Cycle

EOC Problem 4: Alanine and Lactate have identical oxid-state, why do cells get less energy from alanine?

EOC Problem 8: Asp Transaminase activitiy.

Urea Cycle Controlled Acetyl-Glutamate

Acetyl-Glu is in the Arg synthetic pathway in bacteria and plants, in animals it is only regulatory

Benzoate and Phenylbutyrate Given to Lower

Blood Ammonium

Treatment for genetic defects in Urea Cycle

Excreted in Urine

Summary of Amino Acid Catabolism

1 Carbon Transfer Cofactors

Pyruvate Family

Glycine Degradation in Kidney

1. D-amino acid oxidase breaks down D-aa’s from bacterial peptidoglycan.

2. Oxalate-Ca++ are major substance in kidney stones.

Acetyl-SCoA Family

Other Uses of W’s Indole Ring

Phenylalanine Degradation

PKU = Phenylketouria

EOC Problem 11: Analysis of blood and PKU

α-KetoGlutarate Family

Succinyl-SCoA Family

Oxaloacetate Family

Amino Acid Carbon Use

Things to Know and Do Before Class

1. Amino acids from protein are an important energy source in carnivorous animals and during starvation.

2. The first step of AA catabolism is transfer of the NH3 via PLP-dependent aminotransferase usually to -

ketoglutarate to yield L-glutamate.3. In most mammals, toxic ammonia is quickly converted to

carbamoyl phosphate and passed into the urea cycle

4. Amino acids are degraded to pyruvate, acetyl-CoA, α-ketoglutarate, succinyl-CoA, and/or oxaloacetate

5. Amino acids yielding acetyl-CoA are ketogenic.6. Amino acids yielding other end products are glucogenic.7. Genetic defects in amino degradation pathways result in

a number of human diseases: our example is PKU.8. EOC Problems 1-5, 8, 11.