18
Creatine Metabolism

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

Embed Size (px)

Citation preview

Page 1: 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

Creatine Metabolism

Page 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

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

Page 3: 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

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.

Page 4: 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

Three amino acids are required:GlycineArginineMethionine (as S-

adenosylmethionine)

Site of biosynthesis:Step 1: KidneysStep 2: Liver

Creatine Biosynthesis

Page 5: 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

Creatine Biosynthesis

Arginine + Glycine

Ornithine Amidino-transferase

GuanidinoacetateSAM

SAHMethyltransferase

Creatine

Kidneys

Liver

Page 6: 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

From liver, transported to other tissues98% are present in skeletal and heart

musclesIn Muscle, gets converted to the high

energy source creatine phosphate (phosphocreatine)

Distribution of body creatine

Creatine

Creatine phosphate

ATP

ADP + H+

ATP

ADPCreatine Kinase

Page 7: 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

Is 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

Creatine Phosphate

Page 8: 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

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

Page 9: 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

Creatine

Creatine phosphate

ATP

ADP + H+

ATP

ADP

Creatine Kinase

Creatine Degradation

Creatinine

H2O

Pi Plasma

Glomerular filtrationUrine

Page 10: 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

Normal serum creatinine level is 0.7 to 1.4 mg/dL (55-120µmol/L) 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

massSerum creatinine is a sensitive indicator of

kidney disease (Kidney function test)Because normally creatinine is rapidly

removed from the blood and excreted

Creatinine in urine and plasma

Page 11: 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

A typical male excretes about 15mmol of creatinine per day

A decrease in muscle mass due to muscular dystrophy or paralysis leads to decreased level 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/d)

Urinary Creatinine

Page 12: 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

Creatinine is an end product of nitrogen metabolism and is excreted in urine .

Plasma creatinine (PCr) and creatinine clearance (CrCl) are used to assess the kidney functions.

PCr is more precise than (Cr Cl)which depends on urine volume for its calculation

Also PCr is fairly constant through out adult life while (CrCl) declines with aging.

Plasma and Urine Creatininine and Kideny Function

Page 13: 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

CK is responsible for the generation of energy in contractile muscular tissues

CK levels are changed in disorders of cardiac and skeletal muscle

Creatine Kinase (CK)

Creatine

Creatine phosphate

ATP

ADP + H+

ATP

ADP

Creatine Kinase

Page 14: 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

1. CK is required for conversion of creatine into creatine phosphate

2. It is formed of two subunits (B & M)

3. CK has 3 isoenzymes:Skeletal muscle > 98%CK-MM,2 %

CK-MB

Heart muscle 70% CK-MM& 20-30%CK-MB

Brain :lessCK, often CK-BB

These isoenzymes can be seperated according to their physical properties ,eg. using electrophoresis

3

Creatine Kinase (CK)

Page 15: 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
Page 16: 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

Creatine Kinase and muscle disease

There are many enzymes as CK, AST, LD & ALT may be increased in muscle diseases.

Plasma total CK is usually the measurement of choice(largest changes and the greatest number of cases of different aetiologies)

Plasma CK is valuable in the diagnosis of myocardial infarction and some muscle diseases

Increases sometimes large may occur after trauma or surgical operation, intramuscular injections , after prolonged muscular exercise.

Page 17: 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

In Duchenne muscular dystrophy :↑↑ CK at birth before onset of clinical signs , ↑↑↑↑ during early stages of the disease which 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

Page 18: 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

Lippincott, Illustrated BiochemistryBishop : Clinical Chemistry Principles,

Procedures Correlation 6th editionLecture Notes in Clinical Biochemistry

References