A deficiency of ornithine transcarbamylase (OTC) results in which of the following metabolic consequences?

Explanation

## Ornithine Transcarbamylase (OTC) Deficiency **Key Point:** OTC deficiency blocks the second step of the urea cycle, causing carbamoyl phosphate to accumulate and be shunted into the pyrimidine synthesis pathway, leading to elevated carbamoyl aspartate. ### Metabolic Consequences of OTC Deficiency 1. **Urea cycle blockade:** Carbamoyl phosphate cannot condense with ornithine to form citrulline 2. **Carbamoyl phosphate accumulation:** Excess substrate builds up in the mitochondria 3. **Pyrimidine pathway activation:** Carbamoyl phosphate is diverted to CPS II (cytoplasmic), increasing carbamoyl aspartate and pyrimidine synthesis 4. **Hyperammonemia:** Ammonia cannot be fixed into the urea cycle, leading to severe hyperammonemia 5. **Orotic aciduria:** Increased pyrimidine synthesis leads to elevated urinary orotic acid ### Urea Cycle Blockade Mechanism ```mermaid flowchart TD A[Carbamoyl Phosphate]:::outcome --> B{OTC present?}:::decision B -->|Yes| C[Carbamoyl ammonia + Ornithine → Citrulline]:::action B -->|No| D[Carbamoyl phosphate accumulates]:::urgent D --> E[Shunted to Pyrimidine Pathway]:::action E --> F[Elevated Carbamoyl Aspartate]:::outcome E --> G[Orotic Aciduria]:::outcome A --> H[Ammonia NOT fixed]:::urgent H --> I[Hyperammonemia]:::urgent ``` **High-Yield:** OTC deficiency is the most common urea cycle disorder (X-linked inheritance); males are more severely affected than females. **Mnemonic:** **OCAT** — Ornithine + Carbamoyl phosphate → Aspartate (via pyrimidine shunt) + hyperammonemia in OTC deficiency.