creatine metabolism
DESCRIPTION
Energy to Skeletal Muscles Lecture-2. Creatine Metabolism. Objectives. 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 - PowerPoint PPT PresentationTRANSCRIPT
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Creatine Metabolism
Energy to Skeletal Muscles Lecture-2
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• 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
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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.
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Three amino acids are required:GlycineArginineMethionine (as S-adenosylmethionine)
Site of biosynthesis:Step 1: KidneysStep 2: Liver
Creatine Biosynthesis
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Creatine Biosynthesis
Arginine + Glycine
Ornithine Amidino-transferase
Guanidinoacetate
SAM
SAH
Methyltransferase
Creatine
Kidneys
Liver
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• 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
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• 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)
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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
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Creatine
Creatine phosphate
ATP
ADP
ATP
ADP
Creatine Degradation
Creatinine
Pi BLOOD
Kidney
Urine
CREATINEDEGRADATION
IN MUSCLES
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• 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
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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
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• 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
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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.
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• 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
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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
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• Lippincott, Illustrated Biochemistry• Bishop : Clinical Chemistry Principles,
Procedures Correlation 6th edition• Lecture Notes in Clinical Biochemistry
References