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)