OVERVIEW OF METABOLIC

FUNCTIONS OF LIVER

Brajesh Lahri

Final Professional MBBS ,All India Institute of Medical Sciences(AIIMS),Bhopal

METABOLIC FUNCTIONS OF LIVER

Carbohydrate metabolism

Fat metabolism

Protein metabolism

Vitamin Storage

Maintaining iron reserves (Ferritin storage) and production of anti-coagulants

Detoxification

CARBOHYDRATE METABOLISM

Storage of glycogen

Conversion of galactose and fructose to

glucose

Gluconeogenesis

GLYCOGEN STORAGE

GLUCOSE BUFFER FUNCTION

Elevated blood glucose

LiverGlycogen formation

Normal blood glucose

Fall in blood glucose

Liver GlycogenlysisNormal blood

glucose

CARBOHYDRATE METABOLISM

Conversion of galactose and fructose to

glucose

Gluconeogenesis

IF YOU REMEMBER?

CARBOHYDRATE METABOLISM

Gluconeogenesis

GLUCONEOGENESIS

Brain depends on glucose as its primary fuel and red

blood cells use glucose as their only fuel.

Daily requirement=160 g

Glycogen stores= 190 g of glucose

Fall in blood glucose

Liver GlycogenlysisNormal blood

glucose

PROLONGED STARVATION

Depletion of glycogen stores

Fall in glucose levels

Non carbohydrate substances

lactate, amino acids, and glycerol

Gluconeogenesis in the liver and kidney helps to maintain the glucose level in the blood so that brain and muscle can extract sufficient glucose from it to meet their metabolic demands

LIPID METABOLISM

OVERVIEW OF ROLE OF LIVER IN LIPID

METABOLISM

Metabolism of Lipids

Anabolism

Synthesis of de novo cholesterol and fatty acids

Synthesis of fat from proteins and

carbohydrates

Catabolism

Oxidation of fatty acids to supply energy for body

functions

DE NOVO SYNTHESIS OF CHOLESTEROL AND

FATTY ACIDS

Occurs in Liver as well as in peripheral tissues.

For fatty acid synthesis as well as cholesterol synthesis immediate substrate is Acetyl CoA .

SYNTHESIS OF FATS FROM CARBOHYDRATES

AND PROTEINS

• Acetyl CoA from metabolism of Carbon skeleton of proteins

• Acetyl CoA from metabolism of carbohydrates

Acetyl CoA enters lipogenesis

pathway.

BETA OXIDATION OF FATTY ACIDS

OXIDATION OF FATTY ACIDS TO PROVIDE

ENERGY

PROTEINMETABOLISM

MOST IMPORTANT FUNCTIONS OF LIVER

IN PROTEIN METABOLISM

Deamination of amino acids

Formation of urea for removal of ammonia

Formation of plasma proteins

Interconversions of the various amino acids and

synthesis of other compounds from amino acids.

DEAMINATION OF AMINO ACIDS

Required before amino acids can be used for

energy or converted to carbohydrates or fats.

Small amount of deamination occurs in other

tissues especially in kidney

Most important site - liver.

UREA FORMATION

• Deamination

• In gut, by bacteria(small amounts)

Ammonia Formation

• Ammonia enters urea cycle

Urea Formation• Hepatic coma

• Death avoided

Avoids ammonia intoxication

Note: Ammonia freely permeable across blood brain barrier

Ammonia intoxication occurs in

• Severely impaired hepatic function

• Cirrhosis(Collaterals between portal and systemic veins)

UREA FORMATION

FORMATION OF PLASMA PROTEINS

Essentially all plasma proteins, except gamma globulins.

Serum albumin quantitatively the most important

protein synthesized by the liver.

In all chronic liver diseases, serum albumin level is

decreased.

Reversal in A/G ratio occurs in liver cirrhosis, due to

hypoalbuminemia and associated

hypergammaglobulinemia.

Other plasma proteins

Acute phase proteins

Clotting factors

Transport proteins eg. For steroids, hormone transport

AMINO ACID METABOLISM

Synthesis of non-essential amino acids.

Keto acid having same chemical composition as that of the amino acid to be formed is synthesized.

Transamination from an available amino acid is done.

Pyruvat

e

Alanine

Glu or Asp α-ketoglutarate or

oxaloacetete

Eg.

AMINO ACIDS

Essential amino acids

• Arginine

• Histidine

• Isoleucine

• Leucine

• Lysine

• Methionine

• Phenylalanine

• Threonine

• Tryptophan

• Valine

Non Essential Amino Acids

• Alanine

• Asparagine

• Aspartate

• Cysteine

• Glutamate

• Glutamine

• Glycine

• Hydroxyproline

• Hydroxylysine

• Proline

• Serine

• Tyrosine

STORAGE OF VITAMINS IN LIVER

VITAMINS STORED IN LIVER

Vitamin-A

Vitamin-D

Vitamin-B12

VITAMIN-A

Vitamin A is stored in greatest quantity

Maintains blood plasma levels of vitamin A

Prevents vitamin A deficiency for 10 months

MECHANISM OF UPTAKE,STORAGE AND RELEASE OF VITAMIN A

o Vitamin A (Retinol) is transported in chylomicrons as ester of fatty

acids

o Chylomicrons enter circulation;acted on by lipoprotein lipase

o Triglyceride part is reduced;retinyl ester remains unchanged

o Receptors in liver mediate uptake of chylomicron remnants.

o Chylomicron remnants are degraded and retinyl ester is stored

o Liver mobilizes vitamin A by hydrolyzing retinyl ester

o Retinol formed will be bound to retinol binding

protein(RBP),synthesized by liver

HYPERVITAMINOSIS- A

Develops when massive quantities of vitamin A is

consumed

Hepatotoxicity is often associated with

hypervitaminosis A

Eventually leads to portal hypertension and

cirrhosis

VITAMIN- D AND B12

Liver also stores vitamin D and vitamin B12

Liver helps in the activation of vitamin D.

Prevents vitamin D deficiency for 3 to 4 months.

Enough vitamin B12 can be stored in liver for

atleast 1 year.

LIVER: A STORAGE SITE FOR IRON

IRON STORAGE IN LIVER

Liver stores iron mainly in the form of ferritin.

Iron from transferrin in blood transfers to liver and

combines with apoferritin to form ferritin.

WHEN BLOOD IRON LEVEL IS HIGH

Transferriniron in blood

liverFree iron (Fe3+)

Fe3+Fe2+

Fe2+ + apoferritin

ferritin

WHEN BLOOD IRON IS LOW

Transferrin-iron in blood

liver Release of

iron

Fe3+Fe2+

Fe2+ + apoferritin

ferritin

Thus apoferritin-ferritin system of liver acts as

blood iron buffer as well as

iron storage medium.

LIVER: A SITE OF PRODUCTION OF CLOTTING

FACTORS

XIIXIIa

XIXIa

IXIXa

XXa

ProthrombinThrombin

Fibrinogen Fibrin

VIIAIIa

Liver produces :

1)Factor VII

2)Factor IX

3)Factor X

4)Fibrinogen

5)Prothrombin

Extrinsic System

ROLE OF LIVER IN DETOXIFICATION

Liver detoxifies blood of substances originating

from gut or elsewhere in the body

Can be through physical methods or biochemical

reactions

Metabolites are secreted into bile and eliminated

through GIT

Liver detoxification

Physical methods

Kupffer cells

Biochemical reactions

Cyt P450 enzymes mediated

Phase I

oxidation

hydroxylation

Cyt P450 mediated

Phase II

esterification

HEPATIC ENCEPHALOPATHY

Increased level of circulating ammonia due to liver

failure.

Cause-

Loss of functional hepatocytes

Shunting of portal blood

Symptoms-

Confusion

Coma and irreversible change in cognition if untreated