Biochemistry and Foundations of Western Medical Sciences

transcript

Biochemistry and Foundations of Western

Medical SciencesFALL 2011

Dr. Megan Gonzales ND, LAc

Introductions

What you were doing this time last year

What was the best part of your summer before grad school

Why you are here. BE SPECIFIC

What is your favorite biochemical concept/construct

Course Outline

Break it down by week in pairs or trio

Each team has 10 minutes to prepare and 2 minutes to tell the class what they think the class is about the week they are assigned

Cohort has 2 minutes to ask questions

Basic SCIENCES SIOM

1.Biochemistry and Foundations of Western Medical (clinical) Sciences

2. Immunology/Hematology and Microbiology / Infectious Disease (Foundations of Western disease) and Malignant Neoplasms: This includes the HIV/AIDS 7-hr required course - Introduce antimicrobials here

3. Systems I: changes with what is presented in Chinese Medicine course designed to coincide in content to provide a basic understanding of the western diagnosis and treatment at the same time as being presented Chinese illness interpretations.

4. Systems II:

5. Systems III:

6. Systems IV:

Systems View (versus reductionist view)

Article: The Clinical Application of a Systems Approach

Citation: Ahn AC, Tewari M, Poon C-S, Phillips RS (2006) The Clinical Applications of a Systems Approach. PLoS Med 3(7): e209. doi:10.1371/journal.pmed.0030209

The Problem

The primary side effect of a reductionist approach is that the act of reduction (from larger to smaller) disregards component–component interactions and the dynamics that result from them. Therefore, as a general rule, reductionism is less helpful for systems where interactions between components dominate the components themselves in shaping the system-wide behavior

Reductionist versus systems

Big Difference

Application of Both

When to use which...

In clinical medicine, complex, chronic diseases such as diabetes, coronary artery disease, or asthma are examples where this rule may apply. In these examples, a single factor is rarely implicated as solely responsible for disease development or presentation. Rather, multiple factors are often identified, and the disease evolves through complex interactions between them.

continued

Consequently, a perspective in which the interactions and dynamics are centrally integrated into the analytical methods may be better suited. Systems perspectives, unlike reductionisms, focus on these interrelationships and therefore may be the optimal method for complex chronic diseases.

What do you mean?

Where reductionism is helpful, when a systems approach is not, is when one or several components overwhelmingly influence the systems behavior. Diseases such as urinary tract infection, acute appendicitis, or aortic dissection are driven primarily by a single pathology amenable to a specific intervention. Arguably, these conditions would do poorly under a systems approach, where lengthy analysis and comprehensive data acquisition are often required.

Bottom line:

Reductionism works best when an isolatable problem exists and where a quick and effective solution is needed. For that reason, reductionism may generally be most effective for acute and simple diseases, whereas a systems approach may be most applicable to chronic and complex diseases.

The example of diabetes

Given that a systems approach is likely applicable to complex chronic diseases, how might it influence the treatment of a complex disease such as diabetes? Research has shown that diabetes is a multidimensional disorder. Factors such as genetics, inflammation , PPAR-gamma, leptin, cortisol, diet, and body mass index, among others, have been implicated in some form with its pathogenesis.

The role of systems medicine

The fundamental distinctiveness of systems medicine is not just the recognition that these complex factors are important in disease management, but that they need to be incorporated in some meaningful way to treatment selection and delivery.

The diabetes example (from western thought)

Conclusions

The challenges of incorporating systems science into medicine are difficult but not insurmountable. The specific task to be faced is the system-level understanding of human health and disease at the organ, organism, and community level. This effort has great potential for the advancement of medicine.

Questions on Systems thought?

Logical?

FUEL METABOLISM

Acid-Base Biochemistry Acid-Base Biochemistry & Unit ONE& Unit ONE

WEEK 2 SIOMWEEK 2 SIOM

Acid-Base BiochemistryAcid-Base Biochemistry

►DefinitionsDefinitions

►MethodsMethods

►PhysiologyPhysiology

►PathologyPathology

Acid-Base BiochemistryAcid-Base BiochemistryDefinitionsDefinitions

What is an acid?What is an acid?

What is a base?What is a base?

► Definitions of an acidDefinitions of an acid

1.1. TasteTaste

2.2. BoyleBoyle

3.3. ArrheniusArrhenius

4.4. Bronsted-LowryBronsted-Lowry

5.5. LewisLewis

►TasteTaste

– – tasting sour tasting sour

Lemon juice Lemon juice

VinegarVinegar

Definition - Thousands of years oldDefinition - Thousands of years old

►Robert Boyle 17Robert Boyle 17thth century scientist century scientist

►AcidsAcids taste sour, are corrosive to metals, taste sour, are corrosive to metals, change litmus (a dye extracted from change litmus (a dye extracted from lichens) red, and become less acidic when lichens) red, and become less acidic when mixed with mixed with bases (Alkali). (Alkali).

►BasesBases (Alkali) feel slippery, change litmus (Alkali) feel slippery, change litmus blue, and become less basic (alkaline) blue, and become less basic (alkaline) when mixed with when mixed with acids. .

Arrhenius (swedish scientist)Arrhenius (swedish scientist)

►Arrhenius suggested that Arrhenius suggested that acidsacids are are compounds that contain hydrogen and can compounds that contain hydrogen and can dissolve in water to release hydrogen ions dissolve in water to release hydrogen ions into into solution. For example, hydrochloric . For example, hydrochloric acid (HCl) dissolves in water as follows: (HCl) dissolves in water as follows:

HH22OO

HCl HCl (g)(g) →→ H H+ + ((aqaq)) + Cl + Cl--((aqaq))

►Arrhenius defined Arrhenius defined bases as substances that as substances that dissolve in water to release hydroxide dissolve in water to release hydroxide ions (OH(OH--) into ) into solution. For example, a typical . For example, a typical base according to the Arrhenius definition base according to the Arrhenius definition is sodium hydroxide (NaOH): is sodium hydroxide (NaOH):

HH22OO

NaOH NaOH (s)(s) →→ Na Na+ + ((aqaq)) + OH + OH--

((aqaq))

►The Arrhenius definition of The Arrhenius definition of acids and and bases explains a number of things. Arrhenius's explains a number of things. Arrhenius's theory explains why all acids have similar explains why all acids have similar properties to each other (and, conversely, properties to each other (and, conversely, why all bases are similar): because all why all bases are similar): because all acids release Hacids release H++ into into solution (and all bases (and all bases release OHrelease OH--). ).

►The Arrhenius definition also explains The Arrhenius definition also explains Boyle's observation that acids and bases Boyle's observation that acids and bases counteract each other. This idea, that a counteract each other. This idea, that a base can make an acid weaker, and vice base can make an acid weaker, and vice versa, is called versa, is called neutralization..

►NeutralizationNeutralization: As you can see from the : As you can see from the equations, equations, acids release H release H++ into into solution and and bases release OH release OH--. If we were to mix . If we were to mix an acid and base together, the Han acid and base together, the H++ ion would combine with the OHwould combine with the OH-- ion to make ion to make the the molecule H H22O, or plain water:O, or plain water:

►HH+ + ((aqaq)) + OH + OH--

((aqaq) ) →→ H H22OO

►The The neutralization reaction of an reaction of an acid with with a a base will always produce water and a will always produce water and a salt, as shown below: , as shown below:

►Acid Base Water SaltAcid Base Water Salt

►HCl + NaOH HCl + NaOH →→ H H22O + NaClO + NaCl

►HBr + KOH HBr + KOH →→ H H22O + KBrO + KBr

►Limitations of Arrhenius Limitations of Arrhenius

►The Arrhenius definition does not explain The Arrhenius definition does not explain why some substances, such as common why some substances, such as common baking soda (NaHCObaking soda (NaHCO33), can act like a ), can act like a base even though they do not contain hydroxide even though they do not contain hydroxide ions. .

BrBrǿǿnsted-Lowry 1923nsted-Lowry 1923

An acid is any chemical species that donates a An acid is any chemical species that donates a proton to another chemical species (proton proton to another chemical species (proton donor)donor)

A base is any chemical species that accepts a A base is any chemical species that accepts a proton from another chemical species (Proton proton from another chemical species (Proton acceptor)acceptor)

►The Brønsted-Lowry definition of The Brønsted-Lowry definition of acids is is very similar to the Arrhenius definition, any very similar to the Arrhenius definition, any substance that can donate a hydrogen substance that can donate a hydrogen ion is an acid (under the Brønsted definition, is an acid (under the Brønsted definition, acids are often referred to as acids are often referred to as protonproton donors donors because an Hbecause an H++ ion, hydrogen minus its ion, hydrogen minus its electron, is simply a proton). , is simply a proton).

►The Brønsted definition of The Brønsted definition of basesbases is, is, however, quite different from the Arrhenius however, quite different from the Arrhenius definition. Arrhenius base releases definition. Arrhenius base releases hydroxyl ions whereas the Brønsted hydroxyl ions whereas the Brønsted base is is defined as any substance that can accept a defined as any substance that can accept a hydrogen hydrogen ion. .

► The Brønsted-Lowry definition includes the Arrhenius bases The Brønsted-Lowry definition includes the Arrhenius bases soso

► NaOH and KOH, as we saw above, would still be considered NaOH and KOH, as we saw above, would still be considered bases because they can accept an Hbases because they can accept an H++ from an acid to form from an acid to form water.water.

► But it extends the concept of a base and introduces the But it extends the concept of a base and introduces the concept of conjugate acid-base pairs concept of conjugate acid-base pairs

The removal of a proton (hydrogen ion) from The removal of a proton (hydrogen ion) from an acid produces itsan acid produces its conjugate baseconjugate base, which , which is the acid with a hydrogen ion removed, is the acid with a hydrogen ion removed, and the reception of a proton by a base and the reception of a proton by a base produces its produces its conjugate acidconjugate acid, which is the , which is the base with a hydrogen ion addedbase with a hydrogen ion added

► The Brønsted-Lowry definition also explains why substances that do The Brønsted-Lowry definition also explains why substances that do not contain OHnot contain OH-- ions can act like bases. ions can act like bases.

► Baking soda (NaHCOBaking soda (NaHCO33), for example, acts like a base by accepting a ), for example, acts like a base by accepting a

hydrogen ion from an acid as illustrated below: hydrogen ion from an acid as illustrated below:

►Acid Base SaltAcid Base Salt

►HCl + NaHCOHCl + NaHCO33 →→ H H22COCO33 + NaCl + NaCl

► Lewis definition 1923Lewis definition 1923

► A substance that can accept an electron pair from a base A substance that can accept an electron pair from a base is an acid. is an acid.

► The Lewis theory defines an acid as a species that can The Lewis theory defines an acid as a species that can accept an electron pair from another atom, and a base as accept an electron pair from another atom, and a base as a species that can donate an electron pair to complete the a species that can donate an electron pair to complete the valence shell of another atom valence shell of another atom

pHpHUnder the Brønsted-Lowry definition, both Under the Brønsted-Lowry definition, both acids and and bases are related to the are related to the concentration of hydrogen concentration of hydrogen ions present. present. Acids increase the concentration of Acids increase the concentration of hydrogen ions, while bases decrease the hydrogen ions, while bases decrease the concentration of hydrogen ions (by concentration of hydrogen ions (by accepting them). The acidity or basicity of accepting them). The acidity or basicity of something therefore can be measured by something therefore can be measured by its hydrogen ion concentration.its hydrogen ion concentration.

► In 1909, the Danish biochemist Sören Sörensen invented In 1909, the Danish biochemist Sören Sörensen invented the the pH scale for measuring acidity. The pH scale is scale for measuring acidity. The pH scale is described by the formula:described by the formula:

► pH = -log [HpH = -log [H++]]

► Note: concentration is commonly abbreviated by using Note: concentration is commonly abbreviated by using square brackets, thus [Hsquare brackets, thus [H++] = hydrogen ] = hydrogen ion concentration. concentration. When measuring When measuring pH, [H+] is in , [H+] is in units of of moles of H+ per of H+ per litre of litre of solutionsolution..

The Scary Stuff

the equation

Acid-Base BiochemistryAcid-Base BiochemistryPhysiologyPhysiology

►What is Physiological pH range?What is Physiological pH range?

►Extracellular fluid Extracellular fluid

pH 7.35 – 7.46 (35-45 nmol/L)pH 7.35 – 7.46 (35-45 nmol/L)

Does this apply to whole body Does this apply to whole body

?any different pH ranges elsewhere?any different pH ranges elsewhere

More extreme/variable pH rangeMore extreme/variable pH range

Digestive tractDigestive tract

Gastric Juice 1.0-3.0Gastric Juice 1.0-3.0

Pancreatic Juice 8.0-8.3Pancreatic Juice 8.0-8.3

Intercellular organellesIntercellular organelles

Lysosomal pH 4-5Lysosomal pH 4-5

Digestive and lysosomal enzymes are Digestive and lysosomal enzymes are function optimally at these pH rangesfunction optimally at these pH ranges

ph examples

7.4 blood

►WHAT ARE THE SOURCES OF ACID IN THE WHAT ARE THE SOURCES OF ACID IN THE BODY?BODY?

►Sources of acidSources of acid

Metabolism of foodMetabolism of food

Metabolism of drugs Metabolism of drugs

Inborn errors of metabolismInborn errors of metabolism

►Acid production from metabolism of foodAcid production from metabolism of food

Sulphuric acid from metabolism of Sulphuric acid from metabolism of sulphur-containing amino acids of sulphur-containing amino acids of proteinsproteins

Lactic acid from sugarsLactic acid from sugars

Ketoacids from fatsKetoacids from fats

►Acid production from metabolism of drugsAcid production from metabolism of drugs

Direct metabolism of drug to more acidic Direct metabolism of drug to more acidic compound eg salicylates urates etccompound eg salicylates urates etc

Induction of enzymes which metabolise Induction of enzymes which metabolise other compounds (endogenous or other compounds (endogenous or exogenous) to acids exogenous) to acids

►Inborn errors of metabolism Inborn errors of metabolism

Organic acid disordersOrganic acid disorders

Lactic acidosisLactic acidosis

Homeostasis

• The dynamic that defines the distribution of water and the maintenance of pH and electrolyte concentrations

• Water distribution maintained by the kidneys, antidiuretic hormone, hypothalamic thirst response, respiration and perspiration

homeostasis

• Clinically, need to be aware of water depletion caused by decreased intake (coma, wandering the desert) or increased loss (diarrhea, renal malfunction, over-exercise), and excess body water due to increased intake (too much I.V.) or decreased excretion (renal failure)

• Water comprises approx 70% of human mass (45-60% intracellular, 25% extracellular/blood plasma)

Greatest potential source of acid Greatest potential source of acid

Carbon dioxideCarbon dioxide

(1)(1) COCO22 + H + H22O <=> HO <=> H22COCO33

(2) H(2) H22COCO3 3 <=> H<=> H++ + HCO + HCO33--

Potentially 15,000 mmol/24 hoursPotentially 15,000 mmol/24 hours

►Hydrogen ion homeostasisHydrogen ion homeostasis

►1. buffering1. buffering

►2. excretion2. excretion

The buffering system

Buffering of hydrogen ionsBuffering of hydrogen ions

In health as hydrogen ions are produced In health as hydrogen ions are produced they are buffered – limiting the rise in [Hthey are buffered – limiting the rise in [H++]]

Buffer solutions consist of a weak acid and Buffer solutions consist of a weak acid and its conjugate baseits conjugate base

As hydrogen ions are added some will As hydrogen ions are added some will combine with the conjugate base and combine with the conjugate base and convert it to undissociated acidconvert it to undissociated acid

Buffering

Bicarbonate – carbonic acid buffer systemBicarbonate – carbonic acid buffer system

HH++ + HCO + HCO33-- <=> H <=> H22COCO3 (bicar to carbonic acid)3 (bicar to carbonic acid)

►Addition of HAddition of H+ + drives reaction to the rightdrives reaction to the right

Conversely Conversely

►Fall in HFall in H+ + drives reaction to the left as drives reaction to the left as carbonic acid dissociates producing more carbonic acid dissociates producing more HH+ +

►Buffering systems in bloodBuffering systems in blood

Bicarbonate ions-most importantBicarbonate ions-most important

Proteins including intracellular proteinsProteins including intracellular proteins

Haemoglobin Haemoglobin

►Buffer solutions operate most efficiently at Buffer solutions operate most efficiently at [H[H++] that result in approximately equal ] that result in approximately equal concentration of undissociated acid and concentration of undissociated acid and conjugate base conjugate base

►But at normal extracellular fluid pH But at normal extracellular fluid pH

[H[H22COCO33] ] ≅≅ 1.2 mmol 1.2 mmol

whereas [HCOwhereas [HCO33--] is twenty times greater] is twenty times greater

Acid-Base BiochemistryAcid-Base Biochemistry Physiology Physiology

► The bicarbonate system is enhanced by The bicarbonate system is enhanced by the fact that carbonic acid can be formed the fact that carbonic acid can be formed from COfrom CO22 or disposed of by conversion to or disposed of by conversion to COCO22

COCO22 + H + H22O <=> HO <=> H22COCO33

►For every hydrogen ion buffered by For every hydrogen ion buffered by bicarbonate – a bicarbonate ion is bicarbonate – a bicarbonate ion is consumed.consumed.

►To maintain the capacity of the buffer To maintain the capacity of the buffer system, the bicarbonate must be system, the bicarbonate must be regenerated regenerated

►However, when bicarbonate is formed from However, when bicarbonate is formed from carbonic acid (COcarbonic acid (CO22 and H and H22O) equimolar O) equimolar amounts of [Hamounts of [H++] are formed] are formed

►Bicarbonate formation can only continue if Bicarbonate formation can only continue if these hydrogen ions are removedthese hydrogen ions are removed

►This process occurs in the cells of the renal This process occurs in the cells of the renal tubules where hydrogen ions are secreted tubules where hydrogen ions are secreted into the urine and where bicarbonate is into the urine and where bicarbonate is generated and retained in the body and generated and retained in the body and also in the lungs (see next slide)also in the lungs (see next slide)

Some Examples

Questions?

About acids, bases, buffers...

enzymes

Enzymes are protein catalysts for chemical reaction in biological systems. They increase the rate of chemical reactions taking place within living cells with out changing themselves.

Nature of enzymes

Nature of Enzymes

Most enzymes are protein in nature. Depending on the presence and absence of a non- protein component with the enzyme enzymes can exist as, simple enzyme or holoenzyme

Nature of enzymes

Simple enzyme: It is made up of only protein molecules not bound to any non- proteins. Example: Pancreatic Ribonuclease.

Holoenzyme is made up of protein groups and non-protein component. The protein component of this holoenzyme is called apoenzyme

The non-protein component of the holo enzyme is called a cofactor

COenzymes

Coenzymes are derivatives of vitamins without which the enzyme cannot exhibit any reaction. One molecule of coenzyme is able to convert a large number of substrate molecules with the help of enzyme.

Coenzyme accepts a particular group removed from the substrate or donates a particular group to the substrate

Coenzymes are called co substrate because the changes that take place in substrates are complimentary to the changes in coenzymes.

Overview

more terms

ZYMOGENS:Some enzymes are produced in nature in an inactive form which can be activated when they are required, called zymogens

Oxidoreductases

Enzymes catalyzing oxidation reduction reactions. Example: Lactate-dehydrogenase

Lactic acid + NAD+ ---> Pyruvic acid + NADH+H+

transferases

Enzymes catalyzing a transfer of a group other than hydrogen (methyl, acyl, amino or phosphate groups)

hydrolase

Hydrolases: Enzymes catalyzing hydrolysis of ester, ether, peptido, glycosyl, acid-anhydride, C-C, C-halide, or P-N-bonds by utilizing water.

Enzymes that catalyze removal of groups from substances by mechanisms other than hydrolysis, leaving double bonds.

Enzymes acting on C-C, C-O, C-N, C-S and C-halide bonds.

isomerase

Includes all enzymes catalyzing interconversion of optical, geometric, or positional isomers.

Example: Enzymes catalyzing interconversion of aldose and ketoses

ligases and synthetases

Enzymes catalyzing the linking together of 2 compounds coupled to the breaking of a pyrophosphate bond in ATP or similar trinucleotides: GTP, UTP etc. included are enzymes catalyzing reactions forming C-O, C-S, C-N, and C-C bonds,

relevance in medicine

relevance

condensed

activation energy

• For a reaction to proceed from starting material to product, the chemical transformations of bond-making and bond-breaking require a minimal threshold amount of energy, termed activation energy. Generally, a catalyst serves to lower the activation energy of a particular reaction.

transition state

A chemical reaction S-->P (where S is the substrate and P is the product or products) will take place when a certain number of S molecules at any given instant posses enough energy to attain an activated condition called the “transition state”, in which the probability of making or breaking a chemical bond to form the product is very high.

The transition state is the top of the energy barrier separating the reactants and products.

what it looks like

factors affecting enzyme activity

Physical and chemical factors are affecting the enzyme activity. These include

1. Temperature (increases total activity)

2. pH (all enzymes have optimum pH)

3. Substrate/enzyme concentration, etc.(vmax, active site is saturated)

**michaelis menton/lineweaver-burke, fun but not for us this time...

enzyme inhibition

Any substance that can diminish the velocity of an enzyme-catalyzed reaction is called an inhibitor and the process is known as inhibition. There are two major types of enzyme inhibition:

Irreversible

Reversible.

irreversible inhibition

The type of inhibition that can not be reversed by increasing substrate concentration or removing the remaining free inhibitor is called Irreversible inhibition.

Irreversible Inhibitors form strong covalent bonds with an enzyme. These inhibitors may act at, near, or remote from the active site. Consequently, they may not be displaced by the addition of excess substrate. In any case, the basic structure of the enzyme is modified to the degree that it ceases to work.

Penicillin - a suicide substrate

Several drugs in current medical use are mechanism-based

enzyme inactivators.

For example, the antibiotic penicillin exerts its effects by

covalently reacting with an essential serine residue in the

active site of glycoprotein peptidase, an enzyme that acts to

cross-link the peptidoglycan chains during synthesis of

bacterial cell walls.

Once cell wall synthesis is blocked, the bacterial

cells are very susceptible to rupture by osmotic lysis, and

bacterial growth is halted.

reversible inhibition

This type of inhibition can be Competitive, Non-competitive and uncompetitive Competitive Inhibition: This type of inhibition occurs when the inhibitor binds reversibly to the same site that the substrate would normally occupy, therefore, competes with the substrate for that site.

inhibitors, continued

example

General properties

• The biochemical pathways that you will soon be studying are composed of groups of coordinated enzymes that perform a specific metabolic process. In general, these enzyme groups are composed of many enzymes, only a few of which are regulated by the mechanisms described in this lecture.

Allosteric modulation

In addition to simple enzymes that interact only with substrates and inhibitors, there is a class of enzymes that bind small, physiologically important molecules and modulate activity in ways other than those described above called allosteric enzymes

The small regulatory molecules to which they bind are known as effectors.

Allosteric effectors bring about catalytic modification by binding to the enzyme at distinct allosteric sites, well removed from the catalytic site, and causing conformational changes that are transmitted through the bulk of the protein to the catalytically active site(s).

Example of Allosteric modulation

the pathways

• Regulatory enzymes are usually the enzymes that are the rate-limiting, or committed step, in a pathway, meaning that after this step a particular reaction pathway will go to completion.

regulatory enzymes

• Frequently, regulatory enzymes are at or near the initial steps in a pathway, or part of a branch point or cross-over point between pathways (where a metabolite can be potentially converted into several products in different pathways).

general properties

• Recall that when acting as catalysts, enzyme mediated-reactions should be reversible. However, regulatory enzymes frequently catalyze thermodynamically irreversible reactions, that is, a large negative free energy change (-ΔG) greatly favors formation of a given metabolic product rather than the reverse reaction.

where does it happen?

• Thus, regulation of enzyme activity, usually at the committed step of the pathway, is critical for supplying and maintaining cellular metabolitic and energy homeostasis.

how does it happen?

Enzymes in Clinical diagnosis

Plasma enzymes can be classified into two major groups

1. Those relatively small group of enzymes secreted into the plasma by certain organs

2. Those large enzyme species released from cells during normal cell turnover.

In healthy individuals the levels of these enzymes are fairly constant and represent steady state in which the rate of release from cells into the plasma is balanced by an equal rate or removal from the plasma.

When too much is present...

Many diseases that cause tissue damage result in an increased release of intracellular enzymes into the plasma.

The level of specific enzyme activity in the plasma frequently correlates with the extent of tissue damage. Thus, the degree of elevation of a particular enzyme activity in plasma is often useful in evaluating the diagnosis and prognosis for the patient.

LIPASE

It is an enzyme catalyzing the hydrolysis of fats. It is secreted by pancreas and Liver. The plasma lipase level may be low in liver disease, Vitamin A deficiency, some malignancies, and diabetes mellitus. It may be elevated in acute pancreatitis and pancreatic carcinoma.

alpha amylase

α- amylase is the enzyme concerned with the break down of dietary starch and glycogen to maltose. It is present in pancreatic juice and saliva as well as in liver fallopian tubes and muscles. The enzyme is excreted in the Urine. The main use of amylase estimations is in the diagnosis of acute pancreatitis. The plasma amylase level may be low in liver disease and increased in high intestinal obstruction, mumps, acute

trypsin

Trypsin is secreted by pancreas. Elevated levels of trypsin in plasma occur during acute pancreatic disease.

Alk Phos (ALP)

The alkaline phosphates are a group of enzymes, which hydrolyze phosphate esters at an alkaline pH. They are found in bone, liver, kidney, intestinal wall, lactating mammary gland and placenta. In bone the enzyme is found in osteoblasts.

The level of these enzymes may be increased in rickets and osteomalacia, hyperparathyroidism, paget's disease of bone, obstructive jaundice, and metastatic carcinoma. Serum alkaline phosphatase levels may be increase in congestive heart failure result of injury to the liver.

Acid Phosphatases (ACP)

Acid phosphatases catalyzing the hydrolysis of various phosphate esters at acidic pH is found in the prostate, liver, red cells, platelets and bone. It may be elevated in metastatic prostatic carcinoma.

Transaminases

Two transaminases are of clinical interest.

1. AspartateTransaminase, AST,catalyzes the transfer of the amino group of aspartic acid to α- ketoglutarate forming glutamate and oxaloacetate. AST is widely distributed, with high concentration, in the heart, liver, skeletal muscle, kidney and erythrocytes, and damage to any of these tissues may cause raised levels.

2. Alanine Transaminase, ALT, Transfer the amino group of alanine to α- ketoglutarate, forming glutamate and pyruvate. It is present in high concentration in liver and to a lesser extent in skeletal muscle, kidney and heart.

Lactate Dehydrogenase (LDH)

It catalyzes the reversible interconversion of lactate and pyruvate. It is widely distributed with high concentrations in the heart, skeletal muscle, liver, kidney, brain and erythrocytes. The enzyme is increased in plasma in myocardial infarction, acute leukemias, generalized carcinomatosis and in acute hepatitis. Estimation of it isoenzymes is more useful in clinical diagnosis to differentiate hepatic disease and myocardial infarction.

CK, CPK

Creatine kinase (CK) or creatine phosphokinase (CPK) is found in heart muscle brain and skeletal muscle. Measurement of serum creatine phosphokinase activity is of value in the diagnosis of disorders affecting skeletal and cardiac muscle. The level of CPK in plasma highly increased in myocardial infarction.

Is everyone ok??

Biochemistry and Foundations of Western Medical Sciences

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