Methionine amino acid: Essential amino acid Glucogenic: as it gives succinyl CoA It is used as methyl donor. The active form of methionine as methyl donor is S- edenosyl methionine (SAM) +

Functions of methionine: 1- SAM act as methyl donor: for example in: A- synthesis of creatine: Methyl group of creatine is derived from SAM. B- conversion of norepinephrine into epinephrine

Synthesis of creatine (not required, only for illustration)

↓ ↓↓↓↓ Succinyl CoA, so methionine is glucogenic homoserine 2- Methionine ( SAM) participates with serine in the synthesis of cysteine amino acid as follow:

Homocystinuria or hyperhomocysteinemia: Is a genetic disease caused by genetic deficiency of cystathionine synthase leading to accumulation of homomcysteine in blood (hyperhomocysteinemia) and its excretion in urine (homocystinuria). Symptoms: Homocysteine is toxic to CNS, cardiovascular system, kidney, connective tissues, etc. leading to: 1- Mental retardation 2- at chilhood: osteoporosis, bone weakness and fracture (disturb collagen biosynthesis) 3- Cardiovascular diseases: myocardial infarction and atherosclerosis, thrombosis Treatment: restriction of methionine in diet

Cysteine amino acid Non essential, formed from methionine (as before) Glucogenic as it gives pyruvate by Transamination Transamination of cysteine gives β-mercapto pyruvic acid followed by removal of H 2 S giving pyruvate so it is glucogenic.

Functions: 1- Formation of hormones: insulin, oxytocin and vasopressin (ADH) 2- Formation of bile salts: Cysteine enter in the formation of taurine which combine with cholic acid giving bile salts.

3- Formation of cystine (disulfide bond in protein)

Acidic amino acids: Glutamic and aspartic acids Glutamic acid Non essential: as it is synthesized either: -by transamination (see before) Glucogenic: as it gives α-ketoglutarate by transamination

Functions of glutamic acid: 1- Formation of Folic acid: Folic acid is a member of vitamin B complex. It plays an important role in synthesis of purines and TMP and so DNA synthesis. Deficiency of folic acid leads to diminished DNA synthesis and inhibit cell division and inhibit RBCs proliferation resulting in meglaoblastic anemia (accumulation of large, immature RBCs -called megaloblasts- in blood and B.M.). Folic acid is needed for rapid cell division and growth (formation of new cells) as in infancy and pregnancy. Many foods contain folic acid, including vegetables such as spinach, broccoli, green beans, and potatoes. Some food as bread and cereals (corn flakes) are fortified with folic acid. NB: active form of folic acid is called: tetrahydro folic acid (THF) Structure of folic acid (for illustration only) illustrate participation of glutamic acid

Role of THF in purine biosynthesis: THF is the carrier of formate group that constitute the carbons 2 and 8 of purine ring

2- Formation of GABA in brain: by decarboxylation GABA ( γ-amino butyric acid) is an important compound in brain. Drugs that act as agonist of GABA receptors (known as GABA analogues or GABAergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti- convulsive effects. Its deficiency leads to convulsion especially in children. The reaction is PLP- dependent. PLP is derived from vitamin B6, so deficiency of vitamin B6 → deficiency of GABA in brain → convulsion.

3- detoxification of ammonia by formation of glutamine in brain, muscles and liver 4- N3 of pyrimidines and N3, N9 of purines are deived from glutamine | - |

Aspartic acid Non essential: formed through transamination Glucogenic as it gives oxaloacetate by transamination COOH-CH 2 -CH-COOH NH2 |

Functions of aspartate: 1- gives β- alanine by decarboxylation: → -CO2 COOH-CH 2 -CH 2 -NH 2 β- alanine 3- N1 of purines and N1 and C4,5,6 of pyrimidines are derived from aspartate 2- Aspartic has essential role in urea cycle (see before) COOH-CH 2 -CH-COOH | NH2 Aspartic acid

Histidine amino acid Semiessential Glucogenic as it gives glutamic acid which gives α-ketoglutarate by transamination Functions: 1- synthesis of histamine which is local hormone, vasodilatotor substance released in allergic diseases. Histidine Histamine

2- Formation of carnosine and anserine (N-methyl carnosine) by reaction with β-alanine which is derived from aspartate. Carnosine and anserine are found in skeletal muscle of vertebrates and help in muscle contraction. Histidine + β- alanine ↓ -H 2 O Carnosine ↓ SAM Anserine Carnosine is antioxidant that used anti-aging therapy, improve socialization and vocabulary in children with autism.