8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
1/55
Conversion ofAmino acids into
Non-protein
NitrogenousCompounds
Dr. Contessa S. Tac-an
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
2/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
3/55
Glycine
Heme synthesis
Synthesis ofpurines forms positions 4,
5, 7 of the purine ring Constituent ofglutathione
Conjugates with cholic acid to formglycocholic acid
Conjugates with benzoic acid to formhippuric acid
Synthesis ofcreatine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
4/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
5/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
6/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
7/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
8/55
Alanine
Carnosine - is a -alanyl dipeptide
that occurs in human
skeletal muscle. Anserine - also a -alanyl dipeptide
- derived from the diet
- occurs in skeletal muscle
characterized by rapid
contractile activity.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
9/55
Structure of Carnosine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
10/55
Structure ofAnserine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
11/55
Carnosine & Anserine
Functions:
1. Activate myosin ATPaseactivity.
2. Chelate copper and enhance
copper uptake.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
12/55
Cont.
Synthesis: Carnosinesynthetase
-alanine + L-histidine + ATPp
Carnosine + AMP + PPi
Carnosine N-methyltransferaseCarnosine + SAM pSAH
+ Anserine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
13/55
Cont.
Degradation:
Carnosinase
Carnosinep -Alanine + L-Histidine
Carnosinase deficiency - heritabled/o characterized by persistentcarnosinuria.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
14/55
Homocarnosine
CNS dipeptide
Related structurally &metabolically
to carnosine but is present in humanbrain at levels 100x higher thancarnosine levels
Synthesis in brain tissue is catalyzed
by carnosine synthetase
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
15/55
Structure ofHomocarnosine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
16/55
Serine, threonine & tyrosine
Phosphorylation (by proteinkinases) & dephosphorylation
(by protein phosphatases) ofser, thr & tyr serve importantregulatory functions.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
17/55
Serine
Biosynthesis ofsphingosine
Purines & pyrimidinespp
-carbon of ser provides methylgroups of thymine (& of choline)
and of carbons 2 & 8 of purines.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
18/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
19/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
20/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
21/55
Cysteine
Urinary sulfate arises from theoxidation of L-cysteine. (Sulfur ofmethionine contributes to urinarySO4 indirectly, via cysteine.
Precursor of thioethanolamineportion of CoA
Converted to Taurine, thatconjugates with bile acids such as
taurocholic acid
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
22/55
Histidine
Decarboxylation of histidine formshistamine, catalyzed by aromatic L-amino acid decarboxylase orhistidine decarboxylase.
Other histidine compounds include:ergothioneine, carnosine, and
dietary anserine.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
23/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
24/55
Structure of ergothioneine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
25/55
Arginine
Arginine - formamidine donor forcreatine synthesis
Conversion, via ornithine, toputrescine, spermine & spermidine.
Precursor ofnitric oxide (NO), w/c isa neurotransmitter, smooth muscle
relaxant & vasodilator.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
26/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
27/55
Arginine
NO synthase
L-Arginine + O2 + NADPHp
L-Citrulline + NO
Precursor of polyamines, spermine
And spermidine, w/c function in cellproliferation and growth.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
28/55
Spermine & Spermidine
Growth factors for cultured cells.
Stabilization of intact cells,subcellular organelles &membranes.
Pharmacologic doses of polyaminesare hypothermic and hypotensive.
Associate w/ polyanions such asDNA & RNA
Stimulate DNA & RNA synthesis
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
29/55
Cont.
DNA stabilization
Packaging of DNA in bacteriophage
Exert diverse effects in proteinsynthesis
Inhibit protein kinases
Polyamine biosynthesis catalyzedby ornithine decarboxylase.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
30/55
Polyamine biosynthesis
L-ornithine - precursor ofputrescine portion of spermine &spermidine
SAM - precursor ofdiaminopropane portion
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
31/55
Cont.
Enzymes:
1. Ornithine decarboxylase & SAMdecarboxylase - inducible enzymesw/ short half-lives
2. Spermine & Spermidine synthases
- are neither inducible nor
unusually labile enzymes.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
32/55
Ornithine decarboxylase
Half life 10 mins.
Ten- to 200-fold increase in itsactivity after administration tocultured cells ofGH, corticosteroids,testosterone orEGF
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
33/55
SAM decarboxylase
Cofactor: pyruvate
Half life 1-2 hours
Responds to promoters of cellgrowth
Inhibited by decarboxylated SAM
Activated by putrescine
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
34/55
Polyamine degradation
Polyamine oxidase, of liver peroxisomes,oxidizes spermine to spermidine;subsequently oxidizes
spermidine to putrescine. Putrescine oxidizes to NH4 + CO2.
Both aminopropane is converted to -aminopropionaldehyde.
Major fraction of putrescine &spermidine are excreted in urine asconjugates (acetyl derivatives).
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
35/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
36/55
Tryptophan
Forms serotonin
Synthesis/Reactions:
1.
Hydro
xylation of trp to 5-O
Htrp,catalyzed by livertyrosine
hydroxylase
2. Decarboxylation of 5-OHtrp forms
serotonin(5-hydroxytryptamine)
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
37/55
Synthesis of Serotonin
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
38/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
39/55
Serotonin
Potent vasoconstrictor
Stimulator of smooth musclecontraction
Catabolism initiated by monoamineoxidase-catalyzed oxidativedeamination to 5-
hydroxyindoleacetate, excreted inthe urine (2-8mg/d)
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
40/55
Cont.
Malignant carcinoid increasesserotonin production.
Catabolites detected in the urineinclude N-acetylserotoninglucuronide and 5-hydroxyindoleaceturate.
Reduced synthesis of niacin (Vit.B3), causing pellagra.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
41/55
Serotonin forms melatonin
Reactions:
N-acetylation
O-methylation
Melatonin - taken up by all tissues(incl. brain); rapidly metabolized by
hydroxylation at position 6, thenconjugated w/ SO4 or glucuronicacid.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
42/55
Trp metabolites
Excreted in urine and feces
Principal normal urinary catabolitesare 5-hydroxyindoleacetate andindole-3-acetate.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
43/55
Tyrosine
Biosynthesis of melanins, catalyzed bytyrosine hydroxylase.
Neuronal cells convert tyrosine toepinephrine and norepinephrine
Dopamine synthesis, via dopadecarboxylase (B6PO4 as cofactor)
Norepinephrine synthesis catalyzed bydopamine -oxidase(Vit. C and copper
dependent enzyme) Methylation of NE (adrenal medulla)catalyzed by phenylethanolamine-N-methyltransferase, forms epinephrine
Precursor of T3 and T4.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
44/55
Synthesis of cathecolamines
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
45/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
46/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
47/55
ALBINISM
Defective melanin biosynthesis
Hypomelanosis due to heritable defectsin eye and skin melanocytes
Oculocutaneous albinism Forms:
1. Tyrosine hydoxylase negative albinos lack all visual pigment
-- hair bulbs fail to converttyrosine to pigment; melanocytescontain unpigmented melanosomes
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
48/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
49/55
Creatine biosynthesis
Derived from glycine, arginine &methionine
Transfer of guanidino group fromarginine to glycine, formingguanidoacetate(glycocyamine);occurs in kidney
Methylation of guanidoacetate bySAM in the liver
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
50/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
51/55
Cont.
Creatine and phosphocreatine arepresent in muscle, brain & blood.
Forms creatinine (creatineanhydride) in muscle, from creatinePO4 by dehydration & loss ofphosphate
24 hr creatinine excretion in urine isconstant from day to day &proportionate to muscle mass
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
52/55
L-glutamate
Biosynthesis ofK-Aminobutyrate(GABA), via decarboxylation of L-glutamate catalyzed by glutamate
decarboxylase(B6PO4 cofactor)present in CNS
Addtition:
Putrescine can be converted to
GABA, either by deamination (bydiamine oxidase) or via N-acetylatedintermediates.
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
53/55
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
54/55
Cont.
GABA degradation
GABA transaminase
GABAp succinate semi-
aldehyde
Succinate semialdehyde mayundergo either:
1.
Reduction to K-hydro
xybutyrate2. Oxidation to succinate to CO2 &
H2O
8/8/2019 Conversion of Amino acids into Non-protein Nitrogenous Compounds
55/55
Top Related