Amino Acid Biosynthesis & Degradation - PowerPoint Presentation

Slide1

Amino Acid Biosynthesis & Degradation

Learning Objectives :

1. Know the groups of

a.a

. biosynthetic families

2. The enzymes and coenzymes involved in the synthetic pathways

3. The enzyme deficiencies of each pathway.

4. The consequences of the inborn errors of metabolism

Slide2

Amino

Acid Biosynthetic Families,Grouped by Metabolic Precursor

α

-

Ketoglutarate

Pyruvate

Glutamate Alanine

Glutamine

Valine

*

Proline

Leucine

*

Arginine Isoleucine*

3-Phosphoglycerate

Phosphoenolpyruvate

and

Serine

erythrose

4-phosphate

Glycine Tryptophan*

Cysteine Phenylalanine*

Oxaloacetate

Tyrosine

Aspartate

Ribose

5-phosphate

Aspargine

Histidine

*

Methionine*

Threonine*

Lysine*

Slide3

Biosynthetic Families of Amino Acids in Bacteria and Plants

Slide4

Pyruvate as an Entry Point into Metabolism

Pyruvate is the entry point of the three-carbon amino acids alanine, serine, and cysteine into the

metabolic mainstreamThe transamination of alanine directly yields pyruvate.Glutamate is then oxidatively deaminated, yielding NH4+ and regenerating α-ketoglutarate. The sum of these reactions is

Slide5

Another simple reaction in the degradation of amino acids is the

deamination of serine to pyruvate

by serine dehydratase

Slide6

Methionine Metabolism

Slide7

Activated Methyl Cycle. The methyl group of methionine is activated by the formation of

S

adenosylmethionine

Slide8

Oxygenases

Are Required for the Degradation of Aromatic Amino Acids

The degradation of phenylalanine begins with its hydroxylation to tyrosine, a reaction catalyzed by phenylalanine hydroxylase. This enzyme is called a monooxygenase (or mixed-function oxygenase) because one atom of O2 appears in the product and the other in H2O.

Slide9

Phenylalanine & Tyrosine Degradation

Slide10

Phenylalanine

Catabolism Is Genetically Defectivein

Some

People

Genetic

defects

of

amino

acid

metabolism

can

cause

defective

neural

development

and mental

retardation

.

In

most

such

diseases

specific

intermediates

accumulate.

For example

,

a

genetic

defect

in

phenylalanine

hydroxylase

,

The first

enzyme

in

the catabolic

pathway

for

phenylalanine

,

is

responsible

for

the

disease

phenylketonuria

(PKU),

the

most

common

cause

of

elevated

levels

of

phenylalanine

(

hyperphenylalaninemia

).

Slide11

The incidence of phenylketonuria is about 1 in 20,000 newborns. The disease is inherited in an

autosomal recessive

manner. Heterozygotes, who make up about 1.5% of a typical population, appear normal. Carriers of the phenylketonuriagene have a reduced level of phenylalanine hydroxylase, as indicated by an increased level of phenylalanine in the blood

Slide12

Because

the

major outflow pathway is blocked in phenylketonuria, the blood level of phenylalanine is typically at least 20-fold as high as in normal people. Minor fates of phenylalanine in normal people, such as the formation of phenylpyruvate, become major fates in phenylketonurics.

Slide13

Slide14

Alcaptonuria

is an inherited metabolic disorder caused by the absence of homogentisate oxidase.

Slide15

Slide16

The Branched-Chain Amino Acids Yield Acetyl CoA, Acetoacetate,

or

Propionyl CoAThe degradative pathways of valine and isoleucine resemble that of leucine. After transamination and oxidative decarboxylation to yield a CoA derivative, the subsequent reactions are like those of fatty acid oxidation.Isoleucine yields acetyl CoA and propionyl CoA, whereas valine yields CO2 and propionyl CoA.

Slide17

Slide18

Tryptophan Degradation.

The pathway for the conversion of tryptophan into alanine and acetoacetate

Slide19

Histidine

Degradation Conversion of histidine into glutamateGlutamate Formation. Conversion of proline and arginine into glutamate

Slide20

Succinyl CoA Formation.

Conversion of methionine, isoleucine, and

valine into succinyl CoA

Slide21

Some Human Genetic Disorders Affecting Amino Acid Catabolism

Medical condition

Defective processDefective enzymeSymptoms and effectsAlbinismMelanin synthesisfrom tyrosineTyrosine 3-monooxygenase(Tyrosinase)Lack of pigmentation:white hair, pink skinAlkaptonuriaTyrosine degradationHomogentisate

1,2-dioxygenase

Dark

colour

of urine; late developing

Arthritis

Argininemia

Urea synthesis

Arginase

Mental retardation

Slide22

Medical condition

Defective process

Defective enzymeSymptoms and effectsCarbamoyl phosphate synthetase Ideficiency Urea synthesisCarbamoyl phosphatase ILethargy; convulsions;early deathHomocystinuriaMethionine

degradation

Cystathionine

–

β

synthase

Faulty bone development;

mental

retardation

Maple syrup urine disease (branched-

chain

ketoaciduria

)

Isoleucine

,

leucine

,

&

Valine

degradation

Branched-chain –

α

keto

acid

dehydrogenase

complex

Vomiting; convulsions mental retardation, early death

Slide23

Medical condition

Defective process

Defective enzymeSymptoms and effectsMethylmalonic acidemiaConversion of propionyl-CoA to succinyl-CoAMethylmalonyl-CoAmutaseVomiting; convulsions;mental retardation;Early deathPhenylketonuria

Conversion of phenylalanine to tyrosine

Phenylalanine

hydroxylase

Neonatal vomiting

Mental retardation

Slide24

Inherited

defects of

a.a.met. almost result inmental retardation or other developmental abnormalities as a result of harmful accumulation of metabolites .

Slide25

END

of PROTEIN METABOLISM