Post on 15-Jan-2016
Creatine Metabolism
1.To study the importance of creatine in muscle as a storage form of energy
2.To understand the biosynthesis of creatine
3.To study the process of creatine degradation and formation of creatinine as an end product
4.To understand the clinical importance of creatinine as a sensitive indicator of kidney function
5.To study different types of creatine kinase (CK) and their clinical importance
Objectives
Overview •Phosphagen is an energy-rich phosphate compound. Breakdown of a phosphagen such as creatine phosphate enables ATP (adenosine triphosphate) to be generated very quickly without oxygen.
•ATP is the only chemical energy which can be used directly by contracting muscles.
Three amino acids are required:GlycineArginineMethionine (as S-
adenosylmethionine)
Site of biosynthesis:Step 1: KidneysStep 2: Liver
Creatine Biosynthesis
Creatine Biosynthesis
Arginine + Glycine
Ornithine Amidino-transferase
GuanidinoacetateSAM
SAHMethyltransferase
Creatine
Kidneys
Liver
From liver, transported to other tissues98% are present in skeletal and heart
musclesIn Muscle, gets converted to the high
energy source creatine phosphate (phosphocreatine)
Distribution of body creatine
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADPCreatine Kinase
Is a high-energy phosphate compoundActs as a storage form of energy in the
muscleProvides a small but, ready source of
energy during first few minutes of intense muscular contraction
The amount of creatine phosphate in the body is proportional to the muscle mass
Creatine Phosphate
1. Creatine and creatine phosphate spontaneously form creatinine as an end product
2. Creatinine is excreted in the urine
3. Serum creatinine is a sensitive indicator of kidney disease (Kidney function test)
4. Serum creatinine increases with the impairment of kidney function
Creatine Degradation
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
Creatine Degradation
Creatinine
H2O
Pi Plasma
Glomerular filtrationUrine
Normal serum creatinine level is 0.7 to 1.4 mg/dL (55-120µmol/L) and serum creatine level is 0.2 to 0.4mg/dL
The amount of creatinine excreted is proportional to the total creatine phosphate content of the body therefore can be used to estimate muscle
massSerum creatinine is a sensitive indicator of
kidney disease (Kidney function test)Because normally creatinine is rapidly
removed from the blood and excreted
Creatinine in urine and plasma
A typical male excretes about 15mmol of creatinine per day
A decrease in muscle mass due to muscular dystrophy or paralysis leads to decreased level of creatinine in urine
The amount of creatinine in urine is used as an indicator for the proper collection of 24 hours urine sample (normal urinary output is 15-25 mg/kg/d)
Urinary Creatinine
Creatinine is an end product of nitrogen metabolism and is excreted in urine .
Plasma creatinine (PCr) and creatinine clearance (CrCl) are used to assess the kidney functions.
PCr is more precise than (Cr Cl)which depends on urine volume for its calculation
Also PCr is fairly constant through out adult life while (CrCl) declines with aging.
Plasma and Urine Creatininine and Kideny Function
CK is responsible for the generation of energy in contractile muscular tissues
CK levels are changed in disorders of cardiac and skeletal muscle
Creatine Kinase (CK)
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
1. CK is required for conversion of creatine into creatine phosphate
2. It is formed of two subunits (B & M)
3. CK has 3 isoenzymes:Skeletal muscle > 98%CK-MM,2 %
CK-MB
Heart muscle 70% CK-MM& 20-30%CK-MB
Brain :lessCK, often CK-BB
These isoenzymes can be seperated according to their physical properties ,eg. using electrophoresis
3
Creatine Kinase (CK)
Creatine Kinase and muscle disease
There are many enzymes as CK, AST, LD & ALT may be increased in muscle diseases.
Plasma total CK is usually the measurement of choice(largest changes and the greatest number of cases of different aetiologies)
Plasma CK is valuable in the diagnosis of myocardial infarction and some muscle diseases
Increases sometimes large may occur after trauma or surgical operation, intramuscular injections , after prolonged muscular exercise.
In Duchenne muscular dystrophy :↑↑ CK at birth before onset of clinical signs , ↑↑↑↑ during early stages of the disease which tend to fall at the terminal stage
About 75% of female carriers of Duchenne dystrophy have small increases in plasma CK
In neurogenic muscle disease: plasma CK is usually normal in peripheral neuritis, polymyelitis
Lippincott, Illustrated BiochemistryBishop : Clinical Chemistry Principles,
Procedures Correlation 6th editionLecture Notes in Clinical Biochemistry
References