creatine metabolism
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Post on 07-May-2015
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By
Dr Khaled Saleh Algariri
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
What’s Creatine and Creatinine
• Creatine and creatinine are not the samesubstance!• 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).
1. The creatine is an amino acid that does not found in proteins.2. Creatine is a nitrogenous organic acid
Three amino acids are required:GlycineArginineMethionine (as S-
adenosylmethionine)
Site of biosynthesis:Step 1: KidneysStep 2: Liver
Creatine Biosynthesis
Distribution of body creatineFrom liver, transported to other tissues98% are present in skeletal and heart
musclesIn Muscle, gets converted to the high
energy source creatine phosphate (phosphocreatine)Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
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.
The Reversible Equilibrium between Creatine and
Phosphcreatine
Creatine PhosphateIs 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
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 DegradationCreatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
Creatinine
H2O
PiPlasma
Glomerular filtrationUrine
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.
Creatinine Metabolism
The Diagnostic Function of Creatinine
How is Creatinine Used to Monitor Renal Function…?
Levels of Creatinine in the Blood Depends Mainly on Renal Function….but…Is there other factors may affect creatinine level in the blood…?
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.
Creatine Kinase (CK)CK is responsible for the generation of
energy in contractile muscular tissuesCK levels are changed in disorders of
cardiac and skeletal muscle
Creatine
Creatine phosphate
ATP
ADP + H+
ATP
ADP
Creatine Kinase
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)
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
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
Creatinine in urine and plasmaNormal serum creatinine level is 0.7 to 1.4 mg/dl
and serum creatine level is 0.2 to 0.4mg/dlThe 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 excretedThe 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)