1. Synthesis and degradation of Amino acids

2. The catabolism of the amino acids involves:
Overview
The catabolism of the amino acids involves:
Removal of α-amino groups.
Breakdown of the resulting carbon skeletons.
The resulting compounds will be used to form seven intermediate products: oxaloacetate, α-ketoglutarate, pyruvate, fumarate, succinyl coenzyme A (CoA), acetyl CoA, and acetoacetate.
These products directly enter the pathways of intermediary metabolism, resulting either in the synthesis of glucose or lipid or in the production of energy through their oxidation to CO2 and water by the Krebs cycle.

3. Fates of the Carbon Skeletons of Amino Acids
Fates of the Carbon Skeletons of Amino Acids. Glucogenic amino acids are shaded red, and ketogenic amino acids are shaded blue. Most amino acids are both glucogenic and ketogenic.

4. Essential amino acids in humans
Lysine
Methionine
Threonine
Phenylalanine
Tryptophan
Arginine*
Histidine*
Isoleucine
Leucine
Valine
*Required to some degree in young growing period and/or sometimes during illness.

5. Non-essential amino acids in humans
Can be formed from a-keto acids by transamination and subsequent reactions.
Alanine
Asparagine
Aspartate
Glutamate
Glutamine
Glycine
Proline
Serine
Cysteine (from Met*)
Tyrosine (from Phe*)
* Essential amino acids

6. Metabolic relationship of amino acids
BODY PROTEINS
Proteosynthesis
Degradation
AMINO ACIDS
DIETARY
PROTEINS
GLYCOLYSIS
KREBS CYCLE
Digestion
Transamination
NONPROTEIN
DERIVATIVES
Porphyrins
Purines
Pyrimidines
Neurotransmitters
Hormones
Komplex lipids
Aminosugars
UREA
NH3
(Carbon skeleton)
Conversion
250 – 300
g/day
ACETYL CoA
GLUCOSE
CO2
KETONBODIES

7. Biosynthesis of amino acids :transamination reactions All amino acids except threonine, lysine, and proline can be transaminated
amino acid1 +a-keto acid amino acid2 +a-keto acid1
Keto-acid +
Glutamate
Pyridoxal phosphate (PLP)-
dependent aminotransferase +
Amino acid
a-Ketoglutarate

8. Clinicaly important transaminases
Alanine-a-ketoglutarate transferase ALT
(also called glutamate-pyruvate transaminase – GPT)
Aspartate-a-ketoglutarate transferase AST
(also called glutamate-oxalacetate transferase – GOT)
Important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection.
ALT

9. Glucose-alanine cycle
Alanine plays a special role in transporting amino groups to liver.
Ala is the carrier of ammonia and of the carbon skeleton of pyruvate from muscle to liver.
The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.

10. Glucogenic Amino Acids
formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA
Aspartate
Asparagine
Arginine
Proline
Methionine
Valine
Glutamine
Glutamate
Threonine
Alanine
Serine
Cysteine
Glycine
Histidine

11. formed acetyl CoA or acetoacetate
Ketogenic Amino Acids
formed acetyl CoA or acetoacetate
Lysine
Leucine

12. Both glucogenic and ketogenic amino acids
formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA in addition to acetyl CoA or acetoacetate
Isoleucine
Tryptophan
Phenylalanine
Tyrosine

14. The C3 family: alanine, serine, cysteine and threonine are converted to pyruvate

15. The C4 family: aspartate and asparagine are converted into oxalacetate
Aspartic acid
Asparagine
Oxalacetate

16. The C5 family: several amino acids are converted into a-ketoglutarate through glutamate
Glutamine
a-ketoglutarate
Proline
Arginine
Histidine

17. Interconversion of amino acids and intermediates of carbohydrate metabolism and Krebs cycle

18. Synthesis of Ala, Val, and Lue
—Ala, Val, and Lue are derived from pyruvate （EMP）
carbon skeleton

19. Synthesis of Ser, Gly and Cys
—Ser, Gly, and Cys are derived from 3-phosphoglycerate（EMP）
carbon skeleton

20. Synthesis of Glu, Gln, Pro and Arg
—α-Ketoglutarate （TCA） gives rise to Glu, Gln, Pro, and Arg synthesis
carbon skeleton

21. —Oxaloacetate（TCA） gives rise to Asp, Asn, Met, Lys, Thr synthesis
Synthesis of Asp, Asn, Met, Lys,Thr and Arg
—Oxaloacetate（TCA） gives rise to Asp, Asn, Met, Lys, Thr synthesis
carbon skeleton

22. Synthesis of His
carbon skeleton

23. Diseases related to the amino acid metabolism

24. Role of homocysteine in vascular disease
There is a not a proven cause and effect relationship of elevated homocysteine with cardiovascular disease.
Elevated plasma homocysteine levels are an independent cardiovascular risk factor that correlates with the severity of coronary artery disease.
Dietary supplementation with folate, vitamin B12 and vitamin B6 the three vitamins involved in the metabolism of homocysteine to a reduction in circulating levels of homocysteine.

25. Deficiency of phenylalanine hydroxylase (common) or deficiencies in the enzymes that synthesize or reduce the coenzyme BH4.
Elevated levels of phenylalanine, phenyl- lactate, phenylpyruvate in plasma and urine  characteristic mousey odor of urine.
Phenyl ketouria
CNS symptoms: Mental retardation, failure to walk or talk, seizures, hyperactivity, tremor
Hypopigmentation:
deficiency of
pigmentation (fair hair, light skin color, and blue eyes) < hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment melanin

26. Phenyl ketouria Neonatal diagnosis of PKU : laboratory
testing for elevated blood levels of
phenylalanine is mandatory
However, fetus at birth  normal level of phenyl-alanine (mother)  tests performed at birth may show false negative results  exposure of new born to protein diet 24 h after birth  better results.
Treatment of PKU: feeding synthetic amino acid preparations low in phenylalanine, supplemented with some natural foods
Maternal PKU : When mother suffering from PKU + high level on phenylanaline  microcephaly, mental retardation, and congenital heart abnormalities in the fetus
Dietary control of blood phenylalanine prior to conception, and must be maintained throughout the pregnancy

27. which is oxidized to a dark pigment on standing
Alkaptonuria
A rare metabolic disease involving a deficiency in
homogentisic homogentisic tyrosine)
Characteristic
acid oxidase acid
 accumulation
(degenerative pathway of
symptoms:
homogentisic aciduria
which is oxidized to a dark pigment on standing
large joint arthritis and black pigmentation of cartilage and collagenous tissue
Patients are without symptoms till 40
Diets low in protein may help

28. Albinism
A group of conditions with a defect in tyrosine metabolism  a deficiency in the production of melanin  partial or full absence of pigment from the skin, hair, and eyes.
Oculo-cutaneous albinism: due to a deficiency of tyrosinase activity, causing a total absence of pigment from the hair, eyes, and skin
 The most severe form of the condition. Affected people may appear to have white hair, skin, and photophobia (sunlight is painful to their eyes), they sunburn easily, and do not tan.