### Gene Overview: ADH4

**Gene Symbol**: ADH4  
**Chromosomal Location**: Human chromosome 4

The **ADH4** gene encodes for the class II alcohol dehydrogenase 4 (pi subunit), a crucial enzyme that belongs to the alcohol dehydrogenase family. It plays a pivotal role in the metabolism of various substrates, including ethanol, retinol, long-chain aliphatic alcohols, and hydroxysteroids. The enzyme operates as a homodimer and is characterized by its high activity in the oxidation of these substrates.

### Additional Gene Associations

1. **Related Genes**: ADH4 is part of the alcohol dehydrogenase gene cluster located on chromosome 4. Other genes in this cluster include:
   - **ADH1A**, **ADH1B**, **ADH1C** (Class I alcohol dehydrogenases)
   - **ADH2** (also known as "Class II alcohol dehydrogenase", similar to ADH4)
   - **ADH3** (ADH class III)
   This clustering allows for functional overlaps and regulatory interactions. 

### Aging and Age-Related Diseases

1. **Aging**: Alcohol dehydrogenases, including ADH4, may play a role in the metabolism of alcohol and other aging-related substrates, influencing health outcomes related to aging such as liver function and oxidative stress.
   
2. **Age-Related Diseases**: There is emerging evidence suggesting that altered expression or activity of ADH enzymes, including ADH4, may be implicated in:
   - Neurodegenerative diseases, where retinol and its metabolites play crucial roles in neuroprotection and signaling.
   - Metabolic conditions and age-related disorders like diabetes due to its involvement in retinol and fatty acid metabolism.

### Drug Interactions

1. **Known Interactions**: 
   - **Inhibitors**: Drugs like pyrazole can inhibit the enzyme activity of ADH4, which could affect its metabolic processes.
   - **Substrates**: Ethanol is a significant substrate and therefore interacts with the enzyme directly.

2. **Drug Classes**: Due to its metabolic role, ADH4 may be indirectly implicated in drug metabolism, particularly:
   - **Alcohol-Related Drugs**: Disulfiram is one such drug that affects alcohol metabolism and could potentially have downstream effects involving ADH enzymes, including ADH4.

### Pathways and Biological Processes

1. **Biological Pathways**:
   - **Retinoid Metabolism**: ADH4 catalyzes NAD-dependent oxidation of retinol forms, playing a crucial role in vitamin A metabolism.
   - **Fatty Acid Metabolism**: Involvement in the oxidation of omega-hydroxy fatty acids, particularly in converting 20-HETE to eicosatetraenedioate, influences lipid signaling pathways.

2. **Biological Processes**:
   - **Oxidation-Reduction Reactions**: Essential in metabolic processes involving alcohol and various aldehydes.
   - **Eicosanoid Biosynthesis**: The metabolism of arachidonic acid through various pathways leading to lipid mediators.
   - **Response to Oxidative Stress**: By metabolizing reactive alcohols and generation of less toxic products.

In summary, ADH4 is an important gene involved in the metabolism of alcohol and retinol, with associations to various related genes, important roles in aging and age-related diseases, interactions with specific drugs, and participation in key metabolic pathways. Understanding its function and interactions is crucial in the wider context of biochemistry and pharmacology.