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CLINICAL CHEMISTRY (MLT 301)CARBOHYDRATE

LECTURE ONE

Dr. Essam H. Jiffri

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Introduction

Carbohydrates are distributed widely in the body, and have:

- Metabolic functions - Glucose (the principal form and the major fuel for

cellular metabolism)

- Structural functions: - the precursor of other sugars, such as ribose

which is found in: • nucleic acids, and of the • carbohydrate moieties of glycoproteins

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Introduction

Man can synthesize some carbohydrate from substrates such as:

- Glycerol and,

- Amino acids but most is derived from plant sources

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Blood glucose homeostasis

Sources:Blood glucose is maintained from several sources

including:

- Diet- Ingested carbohydrate includes both:

- Digestible form (starch or disaccharides-after digestion are absorbed as glucose, galactose or fructose)

- Nondigestible forms (dietary fibre)

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Blood glucose homeostasis-THE LIVER

The liver is an important organ in blood glucose homeostasis

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Blood glucose homeostasis

-THE LIVER• After feeding (stores some excess glucose as

glycogen)• In the fasted state (through glycogenolysis and

gluconeogenesis, maintains blood levels)• The hepatic uptake and output of glucose is

controlled by: o the concentration of key intermediates, and o The activity of enzymes.

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Blood glucose homeostasis

-THE LIVER• In hepatocytes, glucose phosphorylation is

promoted by glucokinase which has a lower affinity than hexokinase.

• The activity of glucokinase increases with high blood glucose levels and the liver removes glucose from the portal blood after a meal.

• After uptake and phosphorylation, excess glucose is stored in the liver as glycogen.

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Blood glucose homeostasis

Glycogenolysis

- The process by which glucose is released from the liver (phosphorylase the key

regulatory enzyme )

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Blood glucose homeostasis

Glycogenolysis

-In well-fed individuals hepatic glycogen stores can account for up to 10% of organ

weight.

-It forms a buffer which maintains blood glucose levels between meals.

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Blood glucose homeostasisGluconeogenesis

- Other compounds are also converted to glucose in the liver

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Blood glucose homeostasis

Gluconeogenesis

- lactate, glycerol and amino acids, particularly alanine, are gluconeogenic substrates.

- Lactate is continually produced by partial oxidation of glucose in muscle and erythrocytes and is reconverted to glucose in the liver by the (Cori cycle )

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Cori cycle

Liver

Glucose

Lactate

Blood Muscle (glycogen(

Glucose-6-phosphate

Lactate

CO2 + H2O

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Blood glucose homeostasis

Hormonal regulation-carbohydrate-rich meal also affects the release of several hormones:

-Insulin is the major hypoglycaemic hormone

-Other hormones, including glucagon, growth hormone, cortisol and adrenaline are counter-regulatory; these antagonize the effects of: insulin and have gluconeogenic effects.

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Blood glucose homeostasis

Insulin

-Insulin is synthesized by the B (or β) cells in the islets of Langerhans of the pancreas.

-Glucose stimulates insulin release

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Blood glucose homeostasis

Insulin-Insulin is an anabolic hormone whichstimulates: - glucose uptake by muscle and adipose

tissue, and increases:• protein synthesis, • glycogen synthesis• lipogenesis.

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Blood glucose homeostasis

Glucagon

-Glucagon is synthesized in the A (or α) cells of the pancreas.

-Inhibited by glucose and insulin

-Glucagon stimulates:

• glycogenolysis and

• gluconeogenesis (raising blood glucose concentrations).

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Blood glucose homeostasis

Growth Hormone

-Growth hormone secretion is stimulated by hypoglycaemia

-Actions include:

• increased hepatic glucose production, and

• increased lipolysis and raising plasma NEFA levels.

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Blood glucose homeostasis

Adrenaline

-Hypoglycaemia is a potent stimulus for adrenaline secretion.

• Inhibits insulin secretion

• stimulates adipose tissue lipolysis,

• increasing NEF A production

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Blood glucose homeostasis

Cortisol

-Cortisol stimulates:

• hepatic gluconeogenesis

• promotes adipose tissue lipolysis and NEFA release

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INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE

BODY METABOLISM

-Muscle has a higher rate of fuel utilization than other organs during exercise.

-The brain, kidney and intestine utilize a higher percentage of available glucose at rest.

-Alternative fuels are required during prolonged fasting or starvation

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INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE

BODY METABOLISM

-The ketone bodies derived from fatty acid metabolism in the liver :

• acetone

• acetoacetate, and

• β-hydroxybutyrate,

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INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE

BODY METABOLISM

- NEFA from adipose tissue is controlled by:

- the activity of hormon-sensitive lipase.

• Insulin inhibits this enzyme (anti-lipolytic)

• adrenaline, growth hormone, glucagon and cortisol are lipolytic.

- Greater fluxes of NEFAs occur if carbohydrate availability is limited.

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INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE

BODY METABOLISM

-NEFAs are transported in blood bound to albumin; about 30% is extracted by the liver.

-In the liver, NEFAs are either:

• reesterified to form triglycerides or,

• metabolized by Beta-oxidation in mitochondria to form acetyl CoA

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KEY POINTS

Ketone bodies are produced from NEFA in the liver

Ketone bodies are a alternative fuel for brain metabolism

In the starvation many organs utilizeketones, sparing glucose