creatine metabolism

Dr. Vijay Marakala, MBBS, MD.

Senior Lecturer

BIOCHEMISTRY

IMS, MSU.

CREATINE METABOLISM

Synthesis Degradation

CREATINE SYNTHESIS

First step in KIDNEY

Second step in LIVER

CREATINE SYNTHESIS

CREATINE SYNTHESIS REQUIRES THREE AMINO ACIDS

Glycine

Arginine

Methionine

GLYCINE ARGININE

GUANIDOACETATE

ORNITHINE

Arginine-glycine Transaminidase

CREATINE

GuanidoacetoacetateMethyltransferase

S-Adenosylmethionine(SAM)

S-Adenosylhomocysteine(SAH)

In KIDNEY

In LIVER

Distribution of body creatine

From liver, transported to other tissues

98% are present in skeletal and heart muscles

In Muscle, gets converted to the high energy source creatine phosphate

Creatine to creatine

phosphate

CREATINE

CREATINE PHOSPHATE

ATP

ADP

Creatine Kinase In muscle and brain

CREATINE PHOSPHATE

Is a high-energy phosphate compound

Acts as a storage form of energy in

the muscle

The amount of creatine phosphate in the body is proportional to the muscle mass

CREATINE PHOSPHATE – STORE

OF ENERGY IN THE MUSCLE

During muscle contraction the

energy is derived from ATP

hydrolysis.

Thereafter the ATP is regenerated

by hydrolysis of creatine

phosphate

This is called LOHMANN’S

REACTION

DEGRADATION OF CREATINE

Creatine and creatine-P

spontaneously form creatinine

Formation of creatinine is

non-enzymatic

Creatinine is excreted in the

urine

The amount of creatinine excreted per day is constant and depends on body muscle mass

DEGRADATION OF CREATINE

CREATINE

CREATINE PHOSPHATE

ATP

ADP

Creatine Kinase

In muscle and brain

CREATININE

H2O

Pi

Non-enzymatic

DEGRADATION OF CREATINE

CLINICAL SIGNIFICANCE OF

CREATININE

The amount of creatinine excreted from

the body is proportional to the total

creatine phosphate content of the

body, and thus can be used to estimate

muscle mass.

Serum creatinine is a sensitive indicator

of kidney disease (Renal function test)

Serum creatinine increases with the

impairment of kidney function

SERUM CREATININE

SERUM CREATININE

Factors reducing

serum creatinine

Low muscle mass

Malnutrition

Factors increasing serum creatinine

Old age

Renal diseases

Glomerulonephritis

Pyelonephritis

Renal failure

Urinary obstruction

Congestive cardiac failure

URINE CREATININE

The normal daily excretion of creatinine

ranges from 1-2 gm.

A decrease in muscle mass due to muscular dystrophy or paralysis leads to

decreased level of creatinine in urine

Creatinine clearance test is widely used as a measure of the glomerular filtration

rate and is decreased in renal failure

URINE CREATININE

INCREASED

• Acromegaly

• Gigantism

DECREASED

• Later stage of Muscular dystrophy

CLINICAL PEARL

Decreased urinary and blood levels of creatinine indicate

diminished production of

creatinine by skeletal muscle.

However, high blood creatinine levels

could indicate an inability of the kidney

to excrete creatinine, resulting from renal disease.