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  2. Metabolic intermediate
Metabolic intermediate
From Wikipedia, the free encyclopedia
Compounds in biochemical reactions
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Metabolic intermediates are compounds produced during the conversion of substrates (starting molecules) into final products in biochemical reactions within cells.[1]

Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the allosteric regulation of enzymes, glycolysis, the citric acid cycle, and amino acid synthesis.

Metabolic pathways consist of a series of enzymatically catalyzed reactions where each step transforms a substrate into a product that serves as the substrate for the next reaction. Metabolic intermediates are compounds that form during these steps, and they are neither the starting substrate nor the final product of the pathway. These intermediates are crucial because they allow for regulation, energy storage, and extraction of chemical energy in a controlled manner.[2]

Types of Metabolic Intermediates

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Metabolic intermediates can belong to different biochemical classes based on the type of pathway they are involved in. Some examples include:[3]

  • Carbohydrate intermediates: In carbohydrate metabolism, intermediates such as glucose-6-phosphate and fructose-1,6-bisphosphate appear during glycolysis and gluconeogenesis.
  • Amino acid intermediates: During amino acid biosynthesis or degradation, intermediates such as 2-oxoglutarate, pyruvate, or oxaloacetate are produced. These intermediates also link to the citric acid cycle.
  • Lipid intermediates: Fatty acid metabolism involves intermediates like acyl-CoA derivatives during β-oxidation or fatty acid synthesis.
  • Nucleotide intermediates: The metabolism of nucleotides, the building blocks of DNA and RNA, includes intermediates like inosine monophosphate (IMP), which is part of purine biosynthesis.

Clinical significance

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Some can be useful in measuring rates of metabolic processes (for example, 3,4-dihydroxyphenylacetic acid or 3-aminoisobutyrate).

Because they can represent unnatural points of entry into natural metabolic pathways, some (such as AICA ribonucleotide) are of interest to researchers in developing new therapies.

See also

[edit]
  • Metabolism

References

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  1. ^ Muchowska, Kamila B.; Varma, Sreejith J.; Moran, Joseph (May 2019). "Synthesis and breakdown of universal metabolic precursors promoted by iron". Nature. 569 (7754): 104–107. Bibcode:2019Natur.569..104M. doi:10.1038/s41586-019-1151-1. ISSN 1476-4687. PMC 6517266. PMID 31043728.
  2. ^ Voet, Donald; Voet, Judith G. (2011). Biochemistry (4th ed.). Hoboken, NJ: Wiley. ISBN 978-0-470-57095-1.
  3. ^ Berg, Jeremy M.; Tymoczko, John L.; Gatto, Gregory J.; Stryer, Lubert, eds. (2015). Biochemistry (8th ed.). New York, NY: W.H. Freeman/Macmillan. ISBN 978-1-4641-2610-9.
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Fructose and galactose metabolic intermediates
Fructose
  • Fructose-1-phosphate → DHAP/Glyceraldehyde → Glyceraldehyde 3-phosphate
Galactose
  • Galactose-1-phosphate → Glucose 1-phosphate → Glucose 6-phosphate → Fructose 6-phosphate
  • Uridine diphosphate galactose
  • Uridine diphosphate glucose
  • Galactitol
  • Iditol
Mannose
  • Mannose-6-phosphate → Fructose 6-phosphate
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Glycogenesis and glycogenolysis metabolic intermediates
Glucose
  • Glucose 6-phosphate
  • Glucose 1-phosphate
Uridine
  • Uridine diphosphate glucose
  • Uridine triphosphate
Other
  • Glycogen
  • Limit dextran
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Pentose phosphate pathway metabolic intermediates
Oxidative
  • 6-Phosphogluconolactone
  • 6-Phosphogluconate
  • Ribulose 5-phosphate
  • Ribose 5-phosphate
Nonoxidative
  • Xylulose 5-phosphate
  • Sedoheptulose 7-phosphate
  • Erythrose 4-phosphate
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Fatty acid metabolic intermediates
Synthesis
  • Acetyl-CoA
  • Malonyl-CoA
Degradation
  • Acyl-CoA
  • Acetyl-CoA
Peroxisomal
Phytol
  • Phytanic acid
  • Phytanoyl-CoA
  • Pristanic acid
  • Propionyl-CoA
Other
  • Mevalonic acid
  • Very long chain fatty acid
  • v
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Glycoconjugates, lipids, and glycolipids: sphingolipids and glycosphingolipids, and metabolic intermediates
Simple glycosphingolipids
  • Cerebroside
    • Galactocerebroside
    • Glucocerebroside
  • Sulfatide
  • Lactosylceramide
Globosides
  • Globotriaosylceramide
  • Stage-specific embryonic antigen 3
  • Globo H
  • Forssman antigen
Gangliosides
  • GM1
  • GM2
  • GM3
  • GD2
Other
  • Sphingomyelin
  • Sphingosine-1-phosphate
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Cholesterol and steroid metabolic intermediates
Mevalonate pathway
to HMG-CoA
  • Acetyl-CoA
  • Acetoacetyl-CoA
  • HMB
  • HMB-CoA
  • HMG-CoA
Ketone bodies
  • Acetone
  • Acetoacetic acid
  • β-Hydroxybutyric acid
to DMAPP
  • Mevalonic acid
  • Phosphomevalonic acid
  • 5-Diphosphomevalonic acid
  • Isopentenyl pyrophosphate
  • Dimethylallyl pyrophosphate
Geranyl-
  • Geranyl pyrophosphate
  • Geranylgeranyl pyrophosphate
Carotenoid
  • Prephytoene diphosphate
  • Phytoene
Non-mevalonate pathway
  • DOXP
  • MEP
  • CDP-ME
  • CDP-MEP
  • MEcPP
  • HMB-PP
  • IPP
  • DMAPP
To Cholesterol
  • Farnesyl pyrophosphate
  • Squalene
  • 2,3-Oxidosqualene
  • Lanosterol
  • Lanosterol
  • 14-demethyllanosterol
  • 4alpha-Methylzymosterol
  • Zymosterone
  • Zymosterol
  • Zymosterol
  • Zymostenol
  • Lathosterol
  • 7-Dehydrocholesterol
  • Cholesterol
  • Zymosterol
  • Cholesta-7,24-dien-3-ol
  • 7-Dehydrodesmosterol
  • Desmosterol
  • Cholesterol
From Cholesterol
to Steroid hormones
  • 22R-Hydroxycholesterol
  • 20α,22R-Dihydroxycholesterol
  • See here instead.
Nonhuman
To Sitosterol
  • Cycloartenol
  • Cycloeucalenol
  • Obtusifoliol
  • 4α-methylfecosterol
  • Isofucosterol
  • 24-Methylenelophenol
  • Sitosterol
  • More Phytosterols see here instead.
To Ergocalciferol
  • Fecosterol
  • Episterol
  • Ergostatrienol
  • Ergostatetraenol
  • Ergosterol
  • Ergocalciferol
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Amino acid metabolism metabolic intermediates
K→acetyl-CoA
lysine→
  • Saccharopine
  • Allysine
  • α-Aminoadipic acid
  • 2-Oxoadipic acid
  • Glutaryl-CoA
  • Glutaconyl-CoA
  • Crotonyl-CoA
  • β-Hydroxybutyryl-CoA
leucine→
  • β-Hydroxy β-methylbutyric acid
  • β-Hydroxy β-methylbutyryl-CoA
  • Isovaleryl-CoA
  • α-Ketoisocaproic acid
  • β-Ketoisocaproic acid
  • β-Ketoisocaproyl-CoA
  • β-Leucine
  • β-Methylcrotonyl-CoA
  • β-Methylglutaconyl-CoA
  • β-Hydroxy β-methylglutaryl-CoA
tryptophan→alanine→
  • N′-Formylkynurenine
  • Kynurenine
  • Anthranilic acid
  • 3-Hydroxykynurenine
  • 3-Hydroxyanthranilic acid
  • 2-Amino-3-carboxymuconic semialdehyde
  • 2-Aminomuconic semialdehyde
  • 2-Aminomuconic acid
  • Glutaryl-CoA
G
G→pyruvate→
citrate
glycine→
serine→
  • 3-Phosphoglyceric acid
  • glycine→creatine: Glycocyamine
  • Phosphocreatine
  • Creatinine
G→glutamate→
α-ketoglutarate
histidine→
  • Urocanic acid
  • Imidazole propionate
  • Imidazol-4-one-5-propionic acid
  • Formiminoglutamic acid
  • Glutamate-1-semialdehyde
proline→
  • 1-Pyrroline-5-carboxylic acid
arginine→
  • Agmatine
  • Ornithine
  • Citrulline
  • Cadaverine
  • Putrescine
other
  • cysteine+glutamate→glutathione: γ-Glutamylcysteine
G→propionyl-CoA→
succinyl-CoA
valine→
  • α-Ketoisovaleric acid
  • Isobutyryl-CoA
  • Methacrylyl-CoA
  • 3-Hydroxyisobutyryl-CoA
  • 3-Hydroxyisobutyric acid
  • 2-Methyl-3-oxopropanoic acid
isoleucine→
  • 2,3-Dihydroxy-3-methylpentanoic acid
  • 2-Methylbutyryl-CoA
  • Tiglyl-CoA
  • 2-Methylacetoacetyl-CoA
methionine→
  • generation of homocysteine: S-Adenosyl methionine
  • S-Adenosyl-L-homocysteine
  • Homocysteine
  • conversion to cysteine: Cystathionine
  • α-Ketobutyric acid + Cysteine
threonine→
  • α-Ketobutyric acid
propionyl-CoA→
  • Methylmalonyl-CoA
G→fumarate
phenylalanine→tyrosine→
  • 4-Hydroxyphenylpyruvic acid
  • Homogentisic acid
  • 4-Maleylacetoacetic acid
G→oxaloacetate
  • see urea cycle
Other
Cysteine metabolism
  • Cysteine sulfinic acid
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Nucleotide metabolic intermediates
purine
metabolism
anabolism
R5P→IMP:
  • Ribose 5-phosphate (R5P)
  • Phosphoribosyl pyrophosphate (PRPP)
  • Phosphoribosylamine (PRA)
  • Glycineamide ribonucleotide (GAR)
  • Phosphoribosyl-N-formylglycineamide (FGAR)
  • 5′-Phosphoribosylformylglycinamidine (FGAM)
  • 5-Aminoimidazole ribotide (AIR)
  • 5′-Phosphoribosyl-4-carboxy-5-aminoimidazole (CAIR)
  • Phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR)
  • AICA ribonucleotide (AICAR)
  • 5-Formamidoimidazole-4-carboxamide ribotide (FAICAR)
IMP→AMP:
Adenylosuccinate
IMP→GMP:
Xanthosine monophosphate
catabolism
  • 5-Hydroxyisourate
  • Hypoxanthine
  • Uric acid
  • Xanthine
pyrimidine
metabolism
anabolism
  • Carbamoyl aspartic acid
  • Carbamoyl phosphate
  • 4,5-Dihydroorotic acid
  • Orotic acid
  • Orotidine 5'-monophosphate
  • Uridine monophosphate
catabolism
uracil:
  • β-Alanine
  • Dihydrouracil
  • 3-Ureidopropionic acid
thymine:
  • 3-Aminoisobutyric acid
  • Dihydrothymine
  • β-Ureidoisobutyric acid
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Neurotransmitter metabolic intermediates
Catecholamines
Anabolism
  • Phenylalanine → Tyrosine → DOPA (levodopa) → Dopamine → Norepinephrine → Epinephrine
Catabolism
Dopamine
  • 3,4-Dihydroxyphenylacetaldehyde (DOPAL)
  • 3,4-Dihydroxyphenylacetic acid (DOPAC)
  • Homovanillyl alcohol
  • Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET)
  • 3-Methoxytyramine (3-MT)
  • Homovanillic acid (HVA)
Norepinephrine
  • 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL)
  • 3,4-Dihydroxymandelic acid (DHMA)
  • Normetanephrine
  • 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)
  • Vanillylmandelic acid (VMA)
  • 3,4-Dihydroxyphenylethylene glycol (DOPEG, DHPG)
  • 3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG)
Epinephrine
  • 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL)
  • Metanephrine
  • 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)
Tryptophan→Serotonin
Anabolism
  • Tryptophan
  • 5-Hydroxytryptophan (5-HTP)
Catabolism
  • 5-Hydroxyindoleacetaldehyde (5-HIAL)
  • 5-Hydroxyindoleacetic acid (5-HIAA)
  • 5-Hydroxytryptophol (5-HTOL)
Serotonin→Melatonin
  • N-Acetylserotonin (NAS; normelatonin)
  • 5-Methoxytryptamine (5-MT)
  • 5-Methoxyindoleacetaldehyde (5-MIAL)
Trace amines
  • 3-Methoxy-4-hydroxyphenylacetaldehyde (HMPAL)
  • 4-Hydroxyphenylacetaldehyde (HPAL)
  • Indoleacetaldehyde (IAL)
  • Phenacetaldehyde (PAL)
Histamine
  • Histidine
  • 1-Methylhistamine
  • Imidazole acetaldehyde
  • Imidazoleacetic acid (IAA, IMA)
  • 1-Methylimidazoleacetic acid
  • 1,4-Methylimidazolacetic acid
GABA
  • Glutamate
  • Putrescine
  • γ-Aminobutyraldehyde (GABAL)
  • N-Acetylputrescine
  • N-Acetyl-γ-aminobutyraldehyde (N-acetyl-GABAL)
  • N-Acetyl-γ-aminobutyric acid (N-acetyl-GABA)
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Heme metabolic intermediates
Porphyrin biosynthesis
early mitochondrial:
  • D-Aminolevulinic acid
cytosolic:
  • Porphobilinogen
  • Hydroxymethylbilane
  • Uroporphyrinogen III
  • Coproporphyrinogen III
late mitochondrial:
  • Protoporphyrinogen IX
  • Protoporphyrin IX
Heme degradation
and excretion
Breakdown of heme
spleen:
  • Heme → Biliverdin → Bilirubin
blood:
  • Bilirubin+Albumin
liver:
  • Bilirubin glucuronide
  • Bilirubin diglucuronide
Intestine, excretion in feces
  • Stercobilinogen
  • Stercobilin
  • Urobilinogen
Kidney, excretion in urine
  • Urobilin
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Thyroid hormone metabolic intermediates
Tyrosine / iodotyrosine
  • 3-Iodotyrosine
  • Diiodotyrosine
Thyronine / iodothyronine
  • 3'-Monoiodothyronine
  • 3,3'-Diiodothyronine
  • 3,5-Diiodothyronine
  • 3,3',5-Triiodothyronine (T3)
  • 3,3',5'-Triiodothyronine (Reverse T3)
  • 3,5,3',5'-Tetraiodothyronine (Thyroxine, T4)
Thyronamine / iodothyronamine
  • 3-Iodothyronamine
  • 3,3',5-Triiodothyronamine
Iodothyroacetate / iodothyroacetic acid
  • Triiodothyroacetate (TRIAC)
Stub icon

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