creatine metabolism
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Creatine Metabolism
Energy to Skeletal Muscles Lecture-2
• To study the importance of creatine in muscle as a storage form of energy
• To understand the biosynthesis of creatine
• To study the process of creatine degradation and formation of creatinine as an end product
• To understand the clinical importance of creatinine as a sensitive indicator of kidney function
• 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
Guanidinoacetate
SAM
SAH
Methyltransferase
Creatine
Kidneys
Liver
• From liver, transported to other tissues• 98% of creatine are present in skeletal & heart muscles• In muscles, creatine is converted to the high energy source creatine
phosphate (phosphocreatine)
Distribution of body creatine
Creatine
Creatine phosphate
ATP
ADP Creatine Kinase
• 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 seconds of
intense muscular contraction • The amount of creatine phosphate in the body is proportional to the
muscle mass
Creatine phosphate
Creatine Phosphate
Creatine
ADP
ATP ENERGY FOR
MUSCLESDURING EXERCISE
(first few seconds)
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) i.e. serum creatinine increases with the impairment of kidney function
Creatine degradation
Creatine
Creatine phosphate
ATP
ADP
ATP
ADP
Creatine Degradation
Creatinine
Pi BLOOD
Kidney
Urine
CREATINEDEGRADATION
IN MUSCLES
• Normal serum creatinine is 0.7 to 1.4 mg/dl (55-120µmol/L) and serum creatine level is 0.2 to 0.4 mg/dl
• Serum creatinine is a sensitive indicator of kidney disease (Kidney function test) because creatinine is normally rapidly removed from the blood and excreted
• Urinary creatinine can be used to estimate muscle mass As the amount of creatinine excreted in urine is proportional to the total amount of creatine phosphate
of the body & the amount of creatine phosphate in the body is proportional to the muscle mass. A typical male excretes about 15 mmol of creatinine per day A decrease in muscle mass due to muscular dystrophy or paralysis leads to decreased amount 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/day)
Creatinine in urine and plasma
Creatinine is an end product of nitrogen metabolism and is excreted in urine.
Plasma creatinine & creatinine clearance are used to assess the kidney functions (Kidney function tests in labs).
Plasma creatinine Vs. Creatinine Clearance:
1- Plasma creatinine is more precise than creatinine clearance which depends on urine volume for its calculation
2- Plasma creatinine is fairly constant through out adult life while creatinine clearance declines with aging..
S
Plasma creatinine & kidney functions
• Creatine Kinase is responsible for the generation of creatine phosphate in contractile muscular tissues (intracellular).
• Plasma CK levels are changed in disorders of cardiac and skeletal muscle
Plasma Creatine Kinase (CK)
Creatine
Creatine phosphate
ATP
ADP
Creatine Kinase
Creatine Kinase Isoenzymes:
Cretine Kinase (CK) enzyme is a protein formed of two subunits (B & M)
Accordingly, CK has 3 isoenzymes:
CK-3 (CK-MM), CK-2 (CK-MB) & CK-1 (CK-BB)
They have the same function BUT with some difference in structure
Skeletal muscle: > 98% CK-MM & 2 % CK-MB
Heart muscle: 70% CK- MM & 30%CK-MB
Brain : CK-BB
These isoenzymes can be separated using electrophoresis
Plasma Creatine Kinase (CK) cont.
• There are many enzymes as CK, AST & LDH may be increased in muscle diseases.
• Plasma total CK is usually the measurement of choice
• Plasma CK is valuable in the diagnosis of myocardial infarction and some skeletal muscle diseases
• Increase in plasma CK may occur after trauma or surgical operation,
intramuscular injections , after prolonged muscular exercise.
Creatine Kinase & muscle diseases
In Duchenne muscular dystrophy: • Increase in total plasma CK at birth before onset of clinical
signs• Plasma total CK is increased during early stages of the disease
& 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
Creatine Kinase & muscle diseases
• Lippincott, Illustrated Biochemistry• Bishop : Clinical Chemistry Principles,
Procedures Correlation 6th edition• Lecture Notes in Clinical Biochemistry
References
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