Dr

Nasr Elsayed Nasr

برجاء الضغط علي ايكونة الصوت الظاهرة علي كل شريحة لسماع الشرح

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1-Glycine.

• It is non essential , neutral, glucogenic a.a
• it is not optically active (haven't asymmetric carbon atom )

1-Glycine.

can be formed from

CO2+NH3

threonine

serine

choline

Glycine enters in the formation of:

• 1- porphyrins.
• 2- Bile salts
• 3- Glutathione (γ-glutamyl-cysteinyl-�glycine).
• 4-purines: carbons 4,5 and nitrogen 7 are derived from glycine
• 5- Biosynthesis of creatine and creatinine.
• 6- serine
• 7-Detoxication by conjugation

Catabolism of glycine by:�1- glycine synthase (glycine cleavage system )�2-glycine oxidase�glycine by oxidative deamination or by transamination

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glycine oxidase

CH2-NH2-COOH

CHO –COOH

Glyoxylic acid

H –COOH

formic acid

CO2

COOH

COOH

oxalic acid

Glycine.

Glycinuria results from a defect in renal tubular reabsorption.

The defect in primary hyperoxaluria is the failure to catabolize glyoxylate formed by deamination of glycine.

Subsequent oxidation of glyoxylate to oxalate results in urolithiasis, nephrocalcinosis, and early mortality from renal failure or hypertension.

2- Serine :� it is non essential amino acid.�It is glucogenic a.a

Serine hydroxy methyl transferase

PLP

Serine formed from glycine�and 3 phosphoglycerate

• .

COOH

│

CHOH

│

CH2O-P

3 phosph-

oglycerate

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COOH

│

C=O

│

CH2O-P

phospho

Hydroxy

pyruvic acid

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GLU-αkG

COOH

│

CHNH2

│

CH2O-P

3 phospho-

serine

​

COOH

│

CHNH2

│

CH2OH

Serine

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NAD→ NADH+H+

phosphatase

Serine enters in the formation of:

a) phospholipids

CH2-CH-COOH

OH NH2

Phosphatidyl serine (Cephalins)

ethanolamine

Cephalins

lecithins

choline

CO2

3CH3

• B- phosphoproteins
• C- cysteine
• D- source for one carbon moiety
• E-it is lipotropic factors.

3- threonine

it is essential amino acid.

It is glucogenic a.a

Threonine is cleaved to acetaldehyde

and glycine.

Oxidation of acetaldehyde to acetate is followed by formation of acetyl-CoA

(4) Alanine �it is non essential amino acid.�It is glucogenic a.a

5-phenyl alanine �6- tyrosine

• -phenyl alanine it is essential amino acid.�- tyrosine it is non essential amino acid
• They are glucogenic,ketogenic a.a

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Catabolic pathways of phenyl alanine :

1- minor pathways :phenyl alanine by transamination or oxidative deamination forms phenyl pyruvic ,phenyl lactic and phenyl acetic acids.�2- major pathways phenyl alanine is transformed to tyrosine

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• 1-In some cases congenital deficiency of phenyl alanine hydroxylase tyrosine not formed

​

• Lead to increase in phenyl lactic , phenyl Pyruvic ,phenyl acetic increase in blood and appear in urine phenyl Pyruvic oligophrenia

Tyrosine has 4 important pathways

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• 1-pathway of ketone bodies
• 2-Pathway of adrenalin and melanin
• 3- Pathway of thyroxine
• 4-Pathway of phenol (putrefaction)

type I tyrosinemia (tyrosinosis)

• The probable metabolic defect in type I tyrosinemia (tyrosinosis) is at fumaryl acetoacetate hydrolase reaction

.Untreated acute and chronic tyrosinosis leads to death from liver failure

type II tyrosinemia (tyrosinosis)

Alternate metabolites of tyrosine are also excreted in type II tyrosinemia (Richner-Hanhart syndrome), a defect in tyrosine aminotransferase (reaction 1 ),

and in neonatal tyrosinemia, due to lowered p-hydroxy phenyl pyruvate hydroxylase activity (reaction2,.

Alkaptonuria

Alkaptonuria due to defect of homogentisic acid oxidase (reaction 3).

The urine darkens on exposure to air due to oxidation of excreted homogentisic acid .

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Late in the disease, there is arthritis and connective tissue pigmentation (ochronosis)

Parkinson disease

• It occurs in persons with 60 years old and over. It is manifestsd by slowly developing tremors with rigidity in all muscles.
• Treatment by L-dopa

2-pathway of melanin�albinism: deficiency in tyrosinase enzymes

• tyrosine

dopa

dopa quinone

dopa chrome

tyrosinase

7-methionine

it is essential amino acid.

It is glucogenic a.a

It is source of sulfur

It is methyl donner act as lipotropic factor

• Methionine reacts with ATP forming

S-adenosylmethionine, “active methionine”

S-Adenosylmethionine.

Methyl groups are used for synthesis of:

1-creatine from guanidoacetic acid

2-choline from ethanolamine

3-epinephrine from norepinephrine

4-melatonin from N-acetyl serotonin

5-anserine from carnosine

6-Thymine from uracil

7- betaine from glycine

provides sulfur for synthesis of cysteine.

methyltransferase

Methionine adenosyltransferase

adenosylcysteinase

8 -9-cysteine and cystine

it is non- essential amino acid.

It is glucogenic a.a

It enters in the formation of :

A-certain hormones:insulin

B-bile salts

C-glutathione

D-cystine

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Abnormalities of cysteine metabolism.

1- cystinuria: it is an inherited metabolic disease. There is a defect in renal reabsorption of Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria),. Apart from cystine calculi, cystinuria is benign.

2- cystinosis (cystine storage disease) caused by Defective carrier-mediated transport of cystine. with deposition of cystine crystals in tissues and early mortality from acute renal failure.

10- tryptophan

it is essential amino acid.

It is glucogenic a.a and ketogenic a.a.

It have three pathways:

1- Nicotinic acid pathway

2-serotonin pathway

3-Indole and skatole pathway

​

​

ARGENTAFFINOMA (carcinoid)

• Over produce seratonin, normally 1% of tryptophan is converted to serotonin but in carcinoid up to 6% are converted . There is an increase in serotonin catabolites as N-acetylserotonin glucuronide and 5-hydroxy indole acetic acid
• Manifestation: hypertention,bronchial spasm, abdominal pains and diarrhea,flushing

​

• ;

​

​

• ;

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Hartnup disease

• Inborn error in the metabolism of tryptophan
• The intestinal and renal tubular absorption are impaired and excreted in urine
• It is pellagra like skin rash, psychiatric and mental retardation.

11- histidine

it is essential amino acid.

It is glucogenic a.a (converted to glutamic acid)

• The excretion of forminoglutamate, FiGlu in urine due to folate deficiency.( histidine is used as dignostic tool for folate deficiency)

Histidinemia

• This inborn error due to inadequate activities of histidase enzyme leading to impairment of convertion of histidine into urocanic acid .

Histidine

• Formation of :
• 1- histamine
• 2-carnosine and anserine
• 3- ergothionine

• Urinary levels of 3-methylhistidine are unusually low in patients with Wilson’s disease.

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12-13- proline hydroxy proline

it is non essential amino acid.

It is glucogenic a.a

It is formed from glutamic acid

​

14- glutamic acid

it is non essential amino acid.

It is glucogenic a.a

It is formed from α -ketoglutaric acid(ALT).

​

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Glutamic acid

glutamic acid

Enter in the formation of:

1. (GABA) important chemical transmitter in CNS.
2. Glutamine used in detoxicate phenyl acetic
3. Glutamine used in the synthesis of purines
4. Glutathione
5. Proline ,hydroxy proline and ornithine.

​

​

15-Aspartic acid

it is non essential amino acid.

It is glucogenic a.a

It is formed from oxaloacetate (AST).

Formation of :

1-urea cycle

2-purines (N1) and pyramidines (N1,C4,5,6)

3- aspargine by aspargine synthetase.

arginine

it is semi-essential amino acid.

It is glucogenic a.a

Formation of :

1-urea cycle

2-creatine and creatinine.

3- nitric oxide ( by nitric oxide synthase).it is neurotransmitter ,smooth muscle relaxant and vasodilator.

17- valine ,18-leucine,19-isolucine

1- ↓transamination

α-Keto acid

2-↓oxidative decarboxylation

Acyl-CoA thioesters

3-↓-2H

α or βAcyl-CoA thioesters

​

Val

leu

ile

Succinyl CoA

glucognic

PROPIONYL CoA

+AcetylCoA

Glucognic, ketogenic

HMG CoA

ketogenic

Maple syrup urine (branched chain ketonuria)

• It is due to defect of oxidative decarboxylation of α-Keto acid . It cause accumulation of α-Keto acid in tissues and blood leading to ketoacidosis and excreted in urine with odour of burnt sugar .

20- lysine

CH2- (CH2)3-CH-COOH

│ │

NH2 NH2

it is essential amino acid.

It is glucogenic a.a and ketogenic

Lysine and hydroxylysine share in the collagen formation and carnitine.

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The catabolism of Lysine.

Lysine first forms a Schiff base with α-ketoglutarate, which is reduced to saccharopine.

In one form of periodic hyperlysinemia, elevated lysine competitively inhibits liver arginase , causing hyperammonemia. Restricting dietary lysine relieves the ammonemia, whereas ingestion of a lysine load precipitates severe crises and coma.

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In a different periodic hyperlysinemia, lysine catabolites accumulate, but even a lysine load does not trigger hyperammonemia. In addition to impaired synthesis of saccharopine, some patients cannot cleave saccharopine.