Albumin 52203z

ALBUMIN

Group : 1. Kadija Andrews 2. Kimberly Daniels 3. Yonessa Fredricks 4. Jamal Joseph 5. Keisha Kellman 6. Bernard Mc David 7. Faila Ndjelekulu 8. Shekila Isaacs 9. Safiya Victorine 10. Shannon Wright

OBJECTIVES Structure of albumin Biochemical function of albumin Disorders in relation to structure and function Treatment of the disorder

WHAT IS ALBUMIN? 

Protein produced by the liver

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Most abundant protein found in blood plasma

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Involved in multiple function such as transport of small molecules, binding to toxins, maintenance of osmotic or oncotic pressure, etc.

PRIMARY STRUCTURE 

Protein is a single polypeptide chain comprising of 585 amino acids residues

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Contains 17 pairs of disulphide bridges, one free thiol group (cysteine 34) and a single tryptophan (tryptophan 214)

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There are no prosthetic groups

SECONDARY STRUCTURE 

67% of the proteins consists of consist of alpha helices

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There are no beta pleated sheets

TERTIARY STRUCTURE o o o o o

The protein consist of 3 structurally similar globular domains Each domain consists of 2 subdomains; there are six subdomains in all: IA, IB, IIA, IIB, IIIA and IIIB. There are two high binding sites for small heterocyclic or aromatic compounds (on subdomains IIA and IIIA). There are two to three dominant long-chained fatty acids binding site (on subdomains IB and IIIB) There are two distinct metal binding sites, involving cys 34 and the other N terminus, making a total of six ligand binding sites on albumin.

PICTURE SHOWING THE THREE DOMAINS AND SUBDOMAINS OF ALBUMIN

BIOCHEMICAL FUNCTIONS OF ALBUMIN Human serum albumin (HSA), performs multiple functions, including; • Ligand binding • Anti- oxidant • Maintenance of Oncotic pressure • Protective colloid- protein that stabilizes other proteins • Anti- inflammatory

LIGAND BINDING • Binds

and transports many exogenous and endogenous molecules; • Includes transport of fatty acids, metal ions, pharmaceuticals, and metabolites; • Implications for drug delivery and efficacy, detoxification, and antioxidant protection. • Low and High affinity Ligand Binding Sites responsible for binding of most pharmaceuticals • Site 1: large and flexible; tends to bind relatively large heterocyclic compounds(drugs, pesticides, vitamins, antibiotics) or dicarboxylic acids. It also binds to bulky endogenous substances like bilirubin and porphyrins • Site2 (indole-benzodiazepine site) : smaller, less flexible; binding is more stereospecific.

LIGAND BINDING • • • •

Metal Binding; N- terminal binds with high affinity- Cu, Ni, and Co; Au, Ag, and Hg ions bind to cysteine-34 Has relatively weak, nonspecific, latent iron-binding capacity

Antioxidant • An antioxidant is a substance which when present in low or high concentrations prevents the oxidation of oxidizable substrates. • Pro- oxidants-heme; redox- active transition metals like iron and copper(catalyze formation of Reactive Oxygen Substances( ROS), that are toxic) • Primary Antioxidants prevents ROS formation e.g. iron binding antioxidant transferrin • Secondary Antioxidant- scavenge pre- formed ROS. • Albumin reduces their pro- oxidant effect • Prevents damage that toxins may cause to cells by being sacrificed

Maintenance of "osmotic or oncotic pressure” • Functions to maintain  the distribution of extracellular fluid between the vascular and extravas-cular  compartments. •

Oncotic pressure becomes osmotic pressure as the negative charges surrounding the protein molecules attract sodium, thus holding water.

ANTI- INFLAMMATORY •

Accessible thiol group communicates with inflammatory cells depending on its redox state

•

25% albumin has been shown to modulate neutrophil/endothelial cell interactions after shock and resuscitation and to attenuate lung injury.

DISORDER IN RELATION TO STRUCTURE Main Cause of disorder: • Glycation- (sometimes called non-enzymatic glycosylation) is the result of typically covalent bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. This causes impairment of the function of biomolecules and hence alters the structure of the molecules. • serum albumin may undergo a slow non-enzymatic glycation, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction). • Glycation can result in the formation of Advanced Glycation EndProducts (AGE). Accumulation of AGEs leads to tissue damage, stimulation of cellular responses, through receptors specific for AGE-proteins, and generation of reactive oxygen intermediates. AGEs also react with DNA, thus causing mutations and DNA transposition.

DISORDER IN RELATION TO STRUCTURE Glycation gives rise to most functional impairment e.g. failure to function as an antioxidant(becomes oxidative), Binding and transportation of Tryptophan, mutation of genes etc. • The acute loss of albumin in the nephrotic syndrome leads to severe generalized peripheral edema and difficulties in maintenance of normal blood pressure as well as hypocalcemia. • Persons with impaired albumen may incur sleeping disorders. N.B Persons with diabetes are more proned to having glycation of proteins. •

Impaired structure

Normal Albumin structure

DISORDER IN RELATION TO STRUCTURE Biological Impact of Glycation Glycated Albumen has some clinical implications since: • It is involved in the damages associated with Diabetes mellitus, such as Retinopathy, Nephropathy, Neuropathy and Coronary artery disease. • Several in vitro studies have shown the implication of glycated albumin in Platelet activation and aggregation • The lowering aggregation effects of glycated albumin have also been demonstrated in Erythrocytes • Another pathogenic implication of glycated albumin can also be observed in glucose metabolism of both skeletal muscle and adipocyte cells

Disorders in relation to Structure Cont’d • While for some studies glycated albumin is suggested as an alternative marker for glycemic control in many diabetes complications

such

as

Nephropathy,

Retinopathy,

and

Alzheimer’s disease and also in the case of Hemodialysis patients or gestational diabetes. NOTE: It should be noted that in some cases such as Thyroid dysfunction, Nephrotic syndrome or liver cirrhosis in which the amount of albumin is affected then glycerated albumen will no longer be a suitable indicator.

DISORDERS IN RELATION TO FUNCTION What causes the level of albumin to change • The normal level of albumin in adults is 3.5 to 5 g/dL and for children, 4 to 5.9 g/dL. • Plasma levels of albumin may be increased or decreased depending on the disease state. Elevations of serum albumin concentration occur infrequently. Increases resulting from dehydration can be seen when plasma water decreases. Upon rehydration, the albumin level usually returns to normal. • An example of disruption of these pressures is edema. There are several causes of extracellular edema, such as a decrease in plasma proteins that includes albumin. The cause may be an increased loss of proteins (ie, nephrosis, wounds, etc) or failure to produce proteins (ie, liver disease or malnutrition).

DISORDER IN RELATION TO FUNCTION CONT’D A decrease in the albumin level may be the result of decreased synthesis, increased catabolism (use and loss), or combinations of these. A deficiency known as analbuminemia is possible. • The most common cause of decreased plasma albumin levels is related to inflammatory processes (i.e. acute-phase response and chronic inflammatory disorders) • Urinary loss of albumin may lead to decreased levels. What happens if there is a deficit? • Hypoalbuminemia • Hyperalbuminemia

DISORDERS IN RELATION TO FUNCTION CONT’D Hyperalbuminemia • • • • 1.

An increased concentration of human serum albumin in the blood above the normal range of 3.5 and 5 g/dL. Condition is a sign of severe dehydration. Hyperalbuminemia is also linked to Vitamin A deficiency. Also associated with high protein diets. Contributing factors for hyperalbuminemia include: 1. Severe infections 2. Hepatitis 3. Kidney diseases 4. HIV/AIDS 5. Cancer 6. Chronic inflammatory diseases 7. Amyloidosis High levels of albumin in the blood, is actually a symptom of dysfunction within the body.

DISORDERS IN RELATION TO FUNCTION CONT’D Hypoalbuminemia What is hypoalbuminemia? Hypoalbuminemia also known as low albumin is a medical condition where the levels of albumin in the blood are extremely low. Underlying causes of Hypoalbuminemia Some causes of Low albumin levels in the body are: • Renal Dysfunction • Liver Diseases • Certain Heart Conditions • Problems with your stomach • Infections • Side effects of some medication Signs and symptoms of hypoalbuminemia: 1. Swelling all over the body or swelling in a specific part of the body for e.g. in your legs 2. The patient may experience muscle fatigue , weakness or cramps 3. They may experience poor appetite. 4. Specifically patients that have liver problems may notice that the abdomen is swollen with fluids.

TREATMENT OF DISORDER Hypoalbuminemia In order to restore the normal levels of albumin in the body, it is important to treat the underlying cause of the condition. Hypoalbuminemia may be caused by: •

Inadequate nutrition- follow a diet plan that provides the required amount of proteins eg. Milk, eggs,meat,beef,beans and peanut.

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Renal dysfunction- medication, exercise and diet

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Chronic Liver failure- the use of alcohol should be put to an end

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Heart Condition-colchine is useful because it redues inflamination

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Stomach Ailments- conditions such as lymphoma can be treated by chemo radiation or surgery is done based on the stage of the cancer

Lung Infection - people suffering from latent tuberculosis may need one antibiotic, whereas people with active TB(particularly MDR-TB) will often require a prescription of multiple drugs. Hyperalbuminemia In order to treat hyperalbuminemia, the following treatment procedures may be used: •

Chronic dehydration- replacement of fluid orally by consuming water

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Regulating diet.

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Retinol (Vitamin A) deficiency use of artificial tear drops and ointments.

TREATMENT OF THE DISORDER Albumin may be used for treating a variety of conditions, including: • Shock due to blood loss in the body • Burns • Low protein level due to surgery or liver failure • Additional medicine for by surgery Note: Albumin (human) is a concentrate of plasma proteins from human blood. It works by increasing plasma volume or serum albumin levels.

SUMMARY

REFERENCES •

http://www.buzzle.com/articles/high-albumin-levels.html

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http://medicinemosul.uomosul.edu.iq/files/pages/page_2072206.pdf

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http://www.tandurust.com/health-faq-7/albumin-high-levels-causes.html