Page last updated: 2024-10-24

histidine catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of histidine, 2-amino-3-(1H-imidazol-4-yl)propanoic acid. [GOC:go_curators]

Histidine catabolism is the process by which the amino acid histidine is broken down in living organisms. It is a complex pathway involving multiple enzymes and reactions, ultimately leading to the production of ammonia, carbon dioxide, and energy.

**Step 1: Deamination**
Histidine is initially deaminated by the enzyme histidase, producing urocanic acid. This reaction releases ammonia, which is a waste product that needs to be excreted from the body.

**Step 2: Hydration**
Urocanic acid is then hydrated by the enzyme urocanase, forming N-formiminoglutamate (FIGLU).

**Step 3: Tetrahydrofolate-dependent Transfer**
FIGLU is subsequently converted to glutamate by the enzyme formiminotransferase, which requires tetrahydrofolate (THF) as a cofactor. This step involves the transfer of a formimino group (CHNH) from FIGLU to THF, producing N5-formimino-THF.

**Step 4: Formimino-THF Breakdown**
N5-formimino-THF is then converted to N10-formyl-THF by the enzyme formimino-THF cyclodeaminase. This reaction releases ammonia and carbon dioxide.

**Step 5: Glutamate Metabolism**
The glutamate produced in step 3 can enter the citric acid cycle, where it is further oxidized to generate energy.

**Regulation**
The histidine catabolic pathway is tightly regulated to ensure proper balance of histidine and its breakdown products. The activity of histidase, the first enzyme in the pathway, is regulated by feedback inhibition from urocanic acid. Additionally, the availability of THF, a cofactor for formiminotransferase, can influence the rate of histidine catabolism.

**Clinical Significance**
Deficiencies in enzymes involved in histidine catabolism can lead to various genetic disorders, including histidinemia and formiminotransferase deficiency. These disorders can cause neurological problems, developmental delays, and other health issues.

Histidine catabolism is essential for maintaining nitrogen balance, providing energy, and supporting various metabolic processes. It is a complex and highly regulated pathway that plays a crucial role in human health.'
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Proteins (2)

ProteinDefinitionTaxonomy
Histamine N-methyltransferaseA histamine N-methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P50135]Homo sapiens (human)
Histamine N-methyltransferaseA histamine N-methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P50135]Homo sapiens (human)

Compounds (5)

CompoundDefinitionClassesRoles
tacrinetacrine : A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease.

Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
acridines;
aromatic amine
EC 3.1.1.7 (acetylcholinesterase) inhibitor
diphenhydramineantitussive : An agent that suppresses cough. Antitussives have a central or a peripheral action on the cough reflex, or a combination of both. Compare with expectorants, which are considered to increase the volume of secretions in the respiratory tract, so facilitating their removal by ciliary action and coughing, and mucolytics, which decrease the viscosity of mucus, facilitating its removal by ciliary action and expectoration.

diphenhydramine : An ether that is the benzhydryl ether of 2-(dimethylamino)ethanol. It is a H1-receptor antagonist used as a antipruritic and antitussive drug.

Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects.
ether;
tertiary amino compound
anti-allergic agent;
antidyskinesia agent;
antiemetic;
antiparkinson drug;
antipruritic drug;
antitussive;
H1-receptor antagonist;
local anaesthetic;
muscarinic antagonist;
oneirogen;
sedative
metoprinemetoprine: histamine methyltransferase antagonist
s-adenosylhomocysteineS-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine.

S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
adenosines;
amino acid zwitterion;
homocysteine derivative;
homocysteines;
organic sulfide
cofactor;
EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor;
EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor;
epitope;
fundamental metabolite
amodiaquine hydrochloride