METABOLIC PATHWAYS

PATHWAYS

- Enzymatic reactions organized into multi step sequences (e.g Glycolysis)

- product of one reaction serves as the substrate of the subsequent reaction

- Can intersect → integrated and purposeful network of chemical reactions → collectively called METABOLISM

 sum of all the chemical changes occurring in a cell, a tissue, or the body

- can be classified as either catabolic (degradative) or anabolic (synthetic)

METABOLIC MAP

Each pathway is composed of multienzyme sequences, and each enzyme, in turn, may exhibit important catalytic or regulatory features

- Provides a bigger picture

- Contains the important central pathways of energy metabolism

- useful in

 tracing connections between pathways

 visualizing the purposeful “movement” of metabolic intermediates

 picturing the effect on the flow of intermediates if a pathway is blocked

CATABOLIC PATHWAYS

- serve to capture chemical energy in the form of adenosine triphosphate (ATP) from the

- allows molecules in the diet (or nutrient molecules stored in cells) to be converted into building blocks needed for the synthesis of complex molecules

- typically oxidative, and require coenzymes such as NAD+

ANABOLIC PATHWAYS

- combine small molecules, such as amino acids, to form complex molecules, such as proteins

- require energy (are endergonic)

- often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH

GLYCOLYSIS

- also referred to as the Embden-Meyerhof pathway (Germans)

 occurs in cytoplasm

- [in the presence of oxygen] metabolic pathway by which a 6-carbon glucose molecule is oxidized to two molecules of a 3-carbon sugar called pyruvate

- [In the absence of oxygen] pyruvate is converted to Lactate in humans

Embden-Meyerhof pathway

GLYCOLYSIS

generation of ATP and NADH

Production of pyruvate

Production of a variety of six- and three-carbon intermediate compounds

3 principal functions: OF GLYCOLYSIS

Facilitated Transport: GLUT-1 to GLUT-5

 movement of glucose is from high (outside cell) to low (inside) glucose concentration

GLUT-4

: in adipose tissue and skeletal muscle

GLUT-1

: high in RBC but low in muscle cells

CHEMICAL PRIMING PHASE

ENERGY-YIELDING PHASE

PHASES OF GLYCOLYSIS

CHEMICAL PRIMING PHASE

 requires ATP

 also called the preparatory phase or energy investment phase

ENERGY-YIELDING PHASE

 energy-yielding phase which produces ATP

 The 2 trioses are degraded to pyruvate

 NADH can be converted to ATP later

 Production of:

 4 ATP

 NADH

Catalyzed by: Hexokinase, PFK, Pyruvate kinase

all proceed with relatively large free energy decrease

Rate limiting step in Glycolysis

 reaction catalyzed by Phosphofructokinase-1 (PFK1)

 Activated by: AMP, Fructose-6-phosphate and Fructose 2,6 – bisphosphate

 Inhibited by: Citrate, ATP and Glucagon

I. KREBS CYCLE

II. INHIBTORS OF TCA

III. OXIDATIVE PHASE

IV. NON-OXIDATIVE PHASE

V. PENTOSE PHOSPHATE PATHWA

GLUCONEOGENESIS

KREBS CYCLE

 Or Citric Acid Cycle, Tricarboxylic acid (TCA) cycle

 a central driver of cellular respiration (aerobic metabolism)

 Amphibolic: serves in both catabolic and anabolic reactions

 Acetyl CoA → series of redox rxns → harvests much of of its bond E from NADH, FADH2 , and ATP

 Produces reduced electron carriers – NADH and FADH2

Citric Acid Cycle, Tricarboxylic acid (TCA) cycle

KREBS CYCLE

 3 NADH

 1 FADH2

 2 CO2

 1 GTP/ATP per Acetyl-CoA

 4 ATP  NADH

Products OF KREBS CYCLE

Fluoroacetate

 inhibits aconitase; lethal if it accumulates

 is NOT ITSELF TOXIC to cells.

 highly toxic

 Blocks citrate transport in and out of the

 mitochondria

Arsenite (AsO3 3-) and organic compounds

 Binds with dihydrolipoamide and inhibits α ketoglutarate and pyruvate dehydrogenase

Lipoamide

is a factor of α-ketoglutarate and pyruvate dehydrogenase

Oxidation

: breakdown of a molecule as it loses - at least one of its electrons - 2 irreversible steps

STEP 1

 Glucose-6-phosphate is oxidized to form lactone

 NADPH is produced

STEP 2

 Carbon is removed (cleaved)

 CO2 is released

 electrons released from this cleavage is used to reduce NADP+ to NADPH

Ribulose-5-phosphate is produced

NON-OXIDATIVE PHASE

- Reversible reactions

- Ribulose-5-phosphate

: precursor to the sugar that makes up DNA and RNA

STEP 3

 Ribulose-5-phosphate

 Ribose-5-phosphate: used to make up DNA and RNA

 Xylulose-5-phosphate

STEP 4

 produces

 ribose-5-phosphate (from step 3) + another ribose-5-phosphate → 10-carbon molecule

 Excess ribose-5-phosphate → converted into other sugars that can be used by the cell for metabolism

10-Carbon Molecule

o interconverted to create  3-carbon molecule → glycolysis

 From glycolysis → ribose-5-phosphate → DNA/ RNA production

o 7-carbon molecule

STEP 5

 3-C and 7-C molecules:

 4-Carbon molecule: precursor for amino acids

 6-Carbon molecule: used in glycolysis

 Reversible

4-Carbon molecule

precursor for amino acids

6-Carbon molecule

: used in glycolysis

PENTOSE PHOSPHATE PATHWAY (OXIDATIVE PHASE)

-1 H20

+2 NADPH

+1 CO2

PENTOSE PHOSPHATE PATHWAY (NON-OXIDATIVE PHASE)

Ribose 5-phosphate for DNA/RNA building

GLYCOGENESIS

build up, requires ATP

add branching

insulin

Fed state

Glycogenolysis

breakdown of glycogen

debranching enzyme

glucagon, epinephrine

fasting

GLYCOGENOLYSIS

is the production of glucose-6 phosphate by splitting a glucose monomer from glycogen by adding inorganic phosphate

catabolic process

less amount of ATP is consumed

occurs in liver

GLUCONEOGENESIS

is the metabolic process by which glucose is formed from non-carbohydrate precursors in the liver

anabolic process

six ATPS are used in the production of one glucose molecule

occurs in liver and tissues where there is high demand for glucose