protein and amino acid metabolism -...

1Dr. Diala Abu-Hassan00

Protein and Amino Acid

Metabolism

All images were taken from McMurry et al

except where noted

Dr. Diala Abu-Hassan, DDS, PhD

[email protected]

Nursing

mailto:[email protected]

Digestion of Protein

2Dr. Diala Abu-Hassan

Trypsin

Chymotrypsin

Carboxypeptidase

pH 1-2

pH 7-8

Amino Acid Metabolism


Amino Acid Metabolism


Each of the 20 amino acids is degraded via its own unique pathway

General scheme for amino acid catabolism:

• Removal of the amino group

• Use of nitrogen in synthesis of new nitrogen compounds

• Passage of nitrogen into the urea cycle

• Incorporation of the carbon atoms into compounds that can enter the

citric acid cycle

Amino Acid Catabolism: The Amino Group


Transamination The interchange of the amino group of an amino acid and the α-keto group of an acid.

Glutamate fate


The glutamate from transamination serves as an amino group carrier.

Glutamate provides amino groups for the synthesis of new amino acids

Most of the glutamate formed is recycled to regenerate α-ketoglutarate

(oxidative deamination)

Oxidative deamination oxidatively removes the glutamate amino group as

ammonium ion and recycle α -ketoglutarate:

To urea cycle to be eliminated

in the urine as urea

Pathway of nitrogen from an amino acid to urea


The fate of carbons and nitrogens in from amino acid metabolism


Our bodies do not store nitrogen-containing compounds and

ammonia is toxic to cells.

The amino nitrogen must either:

1. Be incorporated into urea and excreted

2. Be used in the synthesis of new nitrogen-containing compounds

Carbon from amino acids enter Kreb’s cycle and the excess is

stored as TAGs (via lipogenesis), glycogen (via gluconeogenesis

and glycogen synthesis), or converted to ketone bodies.

(Nitric oxide (NO, a chemical messenger), Hormones, Neurotransmitters, Heme, Purine and pyrimidine bases (for nucleic acids), Nicotinamide (in NAD+ and NADP+))

Amino Acid Catabolism: The Carbon Atoms


The carbon atoms of amino acids arrive by

distinctive pathways at pyruvate, acetyl-SCoA,

or one of the citric acid cycle intermediates.

All amino acid carbons can be used to generate

energy either by:

1. The citric acid cycle

2. Gluconeogenesis pathway to form glucose

3. Ketogenesis pathway to form ketone bodies

Amino Acid Catabolism: The Carbon Atoms


Both ketogenic and glucogenic amino acids are able to enter

fatty acid biosynthesis via acetyl-SCoA

The Urea Cycle


Urea cycle is the cyclic biochemical pathway that produces urea

for excretion (the conversion of ammonium ion to urea). The cycle

takes place in the liver)

Ammonia is highly toxic and large amount of water is needed to

dilute it, thus it is converted to non-toxic urea via urea cycle.

An energy-rich

phosphate-like ATP

In the mitochondrial matrix:

From oxidative

deamination of amino acids

From CO2 from the Kreb’s cycle

The Urea Cycle


STEPS 1 and 2:

Building Up a Reactive

Intermediate

STEPS 3 and 4:

Cleavage and Hydrolysis

of the Step 2 Product

The Net Result of the Urea Cycle


Formation of urea from the carbon of CO2 and NH4+ and one nitrogen

from the amino acid aspartate, followed by biological elimination

through urine.

Breaking of four high-energy phosphate bonds to provide energy

Production of the citric acid cycle intermediate, fumarate

Diseases associated with ammonia


Hereditary diseases resulting high levels of ammonia in the

blood (hyperammonemia) cause vomiting in infancy, lethargy,

irregular muscle coordination (ataxia), and mental retardation.

Immediate treatment consists of transfusions, blood dialysis

(hemodialysis), and use of chemical agents to remove

ammonia.

Long-term treatment requires a low-protein diet and frequent

small meals to avoid protein overload

Essential Amino Acids


Humans are able to synthesize about half of the 20 amino acids found in proteins

(nonessential amino acids) because they do not have to be supplied by our diet.

The essential amino acids are synthesized only by plants and microorganisms.

Biosynthesis of Nonessential Amino Acids


Reductive deamination is the conversion of an α-keto acid

to an amino acid by reaction with NH4+

All of the nonessential amino acids derive their amino groups

from glutamate

Biosynthesis of Nonessential Amino Acids


Diseases associated with AA synthesis Phenylketonuria (PKU)


Failure to convert phenylalanine to tyrosine causes PKU

PKU causes mental retardation by the second month of life

Treatment consists of a diet low in phenylalanine by eliminating

meat and using low-protein grain products.

Foods sweetened with aspartame (a derivative of phenylalanine)

should be avoided.

Diseases-Gout


Gout is a severely painful condition

caused by the precipitation of sodium urate crystals in joints

Anything that increases the

production of uric acid or

inhibits its excretion in the urine is a possible cause of gout

protein and amino acid metabolism -...

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