2. 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
3. What’s Creatine and Creatinine
• Creatine and creatinine are not the same
substance!
• Creatine is found in the muscles…….
• Creatinine is a break-down product (a
waste product) of creatine phosphate and
creatine in muscles, and is usually
produced at a fairly constant rate by the
body depending on muscle mass).
4. 1. The creatine is an amino
acid that does not found in
proteins.
2. Creatine is a nitrogenous
organic acid
5. Three amino acids are required:
Glycine
Arginine
Methionine (as S-adenosylmethionine)
Site of biosynthesis:
Step 1: Kidneys
Step 2: Liver
Creatine Biosynthesis
6.
7.
8. 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 (phosphocreatine)
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
9. What’s the Relationship between Creatine
and Creatinephosphate?
Creatine and creatine phosphate exist in a
reversible equilibrium in skeletal muscle.
In skeletal muscle, approximately one-fourth of
creatine exists as free creatine and threefourth
exists as creatine phosphate.
11. Creatine Phosphate
Is a high-energy phosphate compound
Acts as a storage form of energy in the muscle
Provides 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
12.
13. 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
15. What is the Fate of Creatinine that was Produced
from Break Down of Creatine Phosphate during
Anaerobic Exercise..?
CREATININE EXCRETION
• The creatinine is a waste product of creatine
phosphate and it will be excreted by the kidney in the
urine at a rate of 1 to 2 g/day.
19. Levels of Creatinine in the Blood
Depends Mainly on Renal
Function….but…
Is there other factors may affect
creatinine level in the blood…?
20. Serum Creatinine may be Affected
Partly by….
The amount of muscle tissue you have. Men tend to
have higher levels of blood creatinine because they
have more skeletal muscle tissues than women.
Protein in diet . Vegetarians have been shown to have
lower creatinine levels in blood.
21. Creatine Kinase (CK)
CK is responsible for the generation of energy in
contractile muscular tissues
CK levels are changed in disorders of cardiac and
skeletal muscle
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
22. 1. CK is required for conversion of creatine into
creatine phosphate
2. CK has 3 isoenzymes:
CK-MM mainly in skeletal muscle
CK-MB mainly in heart muscle
CK-BB mainly in brain
3. Serum total CK is increased in:
Crush injuries (Damage of skeletal muscles)
Myocardial infarction (Damage of heart
muscle)
Creatine Kinase (CK)
23. What is the relation of CK activity in
the blood to tissue damage?
. Diagnostic Value: CK is present in all tissues but
only SELECTIVE RELEASE (brain, muscle but not
liver) therefore different from liver damage
caused by:MI, muscle trauma, muscle dystrophy,
severe exertion, IM injections, hypothyroidism,
chronic alcoholism (with myopathy
24. What is the purpose of assaying for CK over
a period of time?
Isozymes creatine kinase are tissue specific CK is a
dimer of MM, MB, BB isozymes, and only MB is present in
the myocardium (15% TOTAL CK)
MB-CK: myocardial specific injury
- 100% increase in MB-CK within 4 hr
- Peaks at 8-24 hr then decreases, with aminotranserase
change much slower peak ~ 60 hrs , LDH is the best
indicator to follow the MI from third day(To maximize
treatment, prompt recognition essential)
- Usually [CK] cardium & % MB/total CK are constant,
[MB-CK↑] is proportional to degree injury to myo cardium
25. Creatinine in urine and plasma
Normal serum creatinine level is 0.7 to 1.4 mg/dl 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 mass
Serum creatinine is a sensitive indicator of kidney disease
(Kidney function test)
Because normally creatinine is rapidly removed from
the blood and excreted
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)