BASIC METABOLIC BASIC METABOLIC PATHWAYSPATHWAYS

METABOLISMMETABOLISM

Term used to describe the Term used to describe the interconversion of chemical interconversion of chemical compounds in the bodycompounds in the body

It includes;It includes;– Pathways taken by the individual Pathways taken by the individual

moleculesmolecules– Their interrelationships Their interrelationships – Mechanisms that regulate the flow of Mechanisms that regulate the flow of

metabolites through the pathways metabolites through the pathways

Categories of Categories of metabolic pathwaysmetabolic pathways(1) ANABOLIC PATHWAYS(1) ANABOLIC PATHWAYS Involved in the synthesis of larger Involved in the synthesis of larger

and more complex compounds and more complex compounds from smaller precursorsfrom smaller precursors

Eg., synthesis of proteins from Eg., synthesis of proteins from amino acids; synthesis of reserves amino acids; synthesis of reserves of triacylglycerol and glycogenof triacylglycerol and glycogen

EndothermicEndothermic

Categories of Categories of metabolic pathwaysmetabolic pathways(2) CATABOLIC PATHWAYS(2) CATABOLIC PATHWAYS Involved in the breakdown of larger Involved in the breakdown of larger

moleculesmolecules Commonly involving oxidative Commonly involving oxidative

reactionsreactions ExothermicExothermic Producing reducing equivalentsProducing reducing equivalents Mainly via the respiratory chain, Mainly via the respiratory chain,

ATPATP

Categories of Categories of metabolic pathwaysmetabolic pathways

(3) AMPHIBOLIC PATHWAYS(3) AMPHIBOLIC PATHWAYS ““cross roads” of metabolismcross roads” of metabolism Acting as links between the Acting as links between the

anabolic and catabolic pathwaysanabolic and catabolic pathways Example is the citric acid cycleExample is the citric acid cycle

aerobicanaerobic

Source of reducing equivalents (NADPH)

GLUCONEOGENESIS- is the process of

forming glucose from non-carbohydrate precursors (e.g,

lactate, amino acids, and glycerol)

1

2

3

4

Source of fatty acid

Body’s main fuel reserve

1

2

3

Acetoacetate and 3-hydroxybutyrate – important

fuels in prolonged fasting

Essential/nonessential amino acids

1

Gluconeogenesis

32

THE LIVER Glycogenesis Glycogenolysis Gluconeogenesis

Only fuel

 

hydrolysis

Lipogenesis

Largest plasma lipoproteins

Main fuel reserve in the body

Transported to extrahepatic tissues (acting as a fuel in prolonged fasting

Alteration of membrane permeability

GLUCONEOGENESISGLUCONEOGENESIS

Lactate and pyruvate are the Lactate and pyruvate are the substrates which are formed in the substrates which are formed in the cytosol and enter the mitochondrion to cytosol and enter the mitochondrion to yield yield oxaloacetateoxaloacetate (precursor) (precursor)

GLUCOGENIC – amino acids that yield GLUCOGENIC – amino acids that yield pyruvate and 4- and 5- C pyruvate and 4- and 5- C intermediates of the TCA cycleintermediates of the TCA cycle

KETOGENIC – amino acids that give KETOGENIC – amino acids that give rise to acetyl-CoArise to acetyl-CoA

INSULININSULIN Secreted by the Secreted by the -islet cells in response to -islet cells in response to

increased blood glucose concentration (fed state)increased blood glucose concentration (fed state) Controls glucose uptake into the muscle and Controls glucose uptake into the muscle and

adipose tissue adipose tissue GLUT-4 migrate to the cell surface in response to GLUT-4 migrate to the cell surface in response to

insulininsulin Acts to stimulate Acts to stimulate glycogen synthaseglycogen synthase and inhibit and inhibit

glycogen phosphorylaseglycogen phosphorylase (liver and skeletal (liver and skeletal muscles)muscles)

In adipose tissue, it stimulates glucose uptake, its In adipose tissue, it stimulates glucose uptake, its conversion to FA and their esterification to TGconversion to FA and their esterification to TG

Glucose uptake in the liver is insulin independentGlucose uptake in the liver is insulin independent

GLUCAGONGLUCAGON

Secreted by the Secreted by the -cells in -cells in response to the fall in blood response to the fall in blood glucose concentrationglucose concentration

Inhibits Inhibits glycogen synthaseglycogen synthase and and activates activates glycogen phosphorylaseglycogen phosphorylase

In adipose tissue, increase in In adipose tissue, increase in glucagon results to inhibition of glucagon results to inhibition of lipogenesislipogenesis

CLINICAL ASPECTSCLINICAL ASPECTS

Death occurs when essential tissue Death occurs when essential tissue protein are catabolized and not protein are catabolized and not replaced (due to prolonged starvation)replaced (due to prolonged starvation)

KETOSIS results due to high demand for KETOSIS results due to high demand for glucose by the fetus, and lactose glucose by the fetus, and lactose synthesis in lactationsynthesis in lactation

TYPE 1 DIABETES MELLITUS – due to TYPE 1 DIABETES MELLITUS – due to lack of insulin or absence of insulin to lack of insulin or absence of insulin to stimulate glucose uptake and utilization stimulate glucose uptake and utilization