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A 56-year-old man with longstanding poorly controlled diabetes mellitus visits his primary care physician for a follow-up after a recent hospitalization. The patient experienced an episode of acute renal failure while in the hospital, and his creatinine level rose to 3.4 mg/dl (normal, 0.7-1.5 mg/dl).

Creatinine a marker of kidney function, is produced from which of the following precursors?

A. Glutamine, Aspartic acid and CO2

B. Glutamine, Cysteine and Glycine

C. Serine and Palmitoyl Co A

D. Glycine and Succinyl Co A

E. Glycine, Arginine and S-Adenosyl Methionine.

The correct answer is E- Glycine, Arginine and S-Adenosyl Methionine

Creatinine is an anhydrous product of creatine.

Creatine also called, “Methyl guanidoacetic acid”, is produced from Glycine, Arginine and Methionine in the human body primarily in the kidney and liver (figure-1).



Figure-1- In the first step Glycine and Arginine react to form Guanido acetic acid; this reaction takes place in the kidney. In the second step, (in the liver), methylation of guanido acetic acid takes place to form Methyl guanido acetic acid (creatine). Creatine is reversibly phosphorylated to creatine-P by creatine kinase. Creatine phosphate is a high energy compound. Creatinine is produced by the loss of water from creatine.


Creatine is transported in the blood for use by muscles. Approximately 95% of the total creatine is located in skeletal muscle. It is also present in liver, testes and brain. It can occur in free form or phosphorylated form. The phosphorylated form is called ‘Creatine-Phosphate’, ‘Phosphocreatine’ or ‘phosphagen’.

In the skeletal muscle creatine is reversibly phosphorylated, The reaction is catalyzed by Creatine kinase, also called Creatine phospho kinase (CPK). The physiological role of creatine phosphate is to form a rapidly available reserve of energy-rich phosphate groups.

There are 3 main isoenzymes of CPK, which are present in brain (CPK-BB), myocardium (CPK-MB) and skeletal muscle (CPK-MM). High CPK-MB in plasma is an early marker of Acute myocardial infarction, whereas high CPK-MM is a marker of muscle injury or muscular disorder.

Creatine is excreted in the form of Creatinine, which is formed by removal of one molecule of water from creatine.

Creatine————–> Creatinine + H20

The reaction is non- enzymatic and irreversible. About 2 % of the total Creatine is converted daily to creatinine so that the amount of creatinine produced is related to the total muscle mass and remains approximately the same in plasma and urine from day-to-day unless the muscle mass changes.

Creatinine is mostly eliminated through kidney by glomerular filtration. Normal excretion ranges between 1-2 g/day.  Estimation of serum and urinary creatinine is undertaken to assess the renal functions. Creatinine clearance estimation is undertaken to determine Glomerular filtration rate (GFR). The normal serum creatinine ranges as follows :

1) < 12 Years-0.25-0.85 mg/dL

2) Adult male 0.7-1.5 mg/dL

3) Adult female 0.4 -1.2 mg/dL

It is higher in males because of the muscle mass.

As regards other options

A. Glutamine, Aspartic acid and CO2- these three along with ATP are needed for the synthesis of pyrimidine nucleotides.

B. Glutamine, Cysteine and Glycine- there is no peptide or compound formed from these amino acids. Glutamic acid, cysteine and glycine are required for the formation of Glutathione.

C. Serine and Palmitoyl Co A condense to form Sphingol, which is required for the synthesis of sphingolipids.

D. Glycine and Succinyl Co A are required for the heme biosynthesis.







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