Metabolic

Pathways

Kyoto Encyclopedia

Stages of Catabolism

MET. OF CARBOHYDRATE

(NADPH + PENTOSE)

PPP
UAP

GLIKOGEN

GLIKOGENESIS

GLIKOGENOLISIS

GLUKOSA

URONIC ACID

GLUKONEOGENESIS

GLIKOLISIS

PIRUVAT

ASETIL-KoA

OXALOACETAT
TCA cycle

SITRAT

Glucose metabolism

Hexokinase Traps Glucose in the Cell and Begins Glycolysis

Kinases are enzymes that catalyze the transfer of a phosphoryl

group from ATP to anacceptor.

(AEROBIC)

(ANAEROBIC)

Isomerization of glucose 6-phosphate to fructose 6-phosphate.

Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6-bisphosphate

(F-1,6-BP).

Regulation of Glycolysis

Phosphofructokinase is the key enzyme in the regulation of glycolysis.

The Six-Carbon Sugar Is Cleaved into Two Three-Carbon Fragments by

Aldolase

Isomerase Salvages a Three-Carbon Fragment

Mechanism of oxidation of glyceraldehyde 3phosphate

Formation of ATP from 1,3-Bisphosphoglycerate

Generation of Additional ATP and the Formation of Pyruvate

H2O

ANAEROBIC CONDITION

The reduction of pyruvate by NADH to form lactate occurs

when the amount of oxygen is limited.

Summary of Glycolysis

(AEROBIC)

(ANAEROBIC)

Tissues That Function Under Hypoxic

Circumstances Tend to Produce Lactate
skeletal muscle (particularly the white fibers)
erythrocytes (lack mitochondria)
brain
gastrointestinal tract
renal medulla
retina
skin

In Erythrocytes, the First Site in Glycolysis

for ATP Generation May Be Bypassed

Generation of high-energy phosphate in the catabolism

of glucose

Entry Points in Glycolysis for Galactose and Fructose

Fructose Metabolism. Fructose enters the glycolytic

pathway in the liver through the fructose 1-phosphate
pathway.

Galactose Metabolism

Metabolism of Glycogen
BIOMEDICAL IMPORTANCE
Glycogen is the major storage carbohydrate in
animals
Mainly in liver and muscle
Muscle glycogen : source of glucose for glycolysis
within the muscle itself
Liver glycogen : store and export glucose to
maintain blood glucose

biosynthesis of glycogen

UDPglucose
pyrophosphorylase

glycogen synthase

Steps in glycogenolysis

Glycogen
phosphorylase

Glycogen metabolism

Control of glycogen synthase in muscle

INSULIN

+
EPINEPHRINE
NOR-EPINEPHRINE
GLUCAGON
THYROXINE

Control of phosphorylase in muscle

INSULIN

+
EPINEPHRINE
NOREPINEPHRINE
GLUCAGON
THYROXINE

Pathway of Glycogenesis and of Glycogenolysis in the Liver

GLYCOGENESIS

GLYCOGENOLYSIS

Coordinated control of glycogenolysis and glycogenesis by cAMPdependent protein kinase

Glycogen balance

Glycogen storage diseases

Diabetes mellitus
(absolute or relative insulin deficiency)
affects carbohydrate and lipid metabolism
occurs in two forms :
type 1 diabetes (insulin-dependent diabetes
mellitus, IDDM)
the insulin-forming cells are destroyed in young individuals by an
autoimmune reaction

type 2 diabetes (noninsulin-dependent diabetes

mellitus, NIDDM)
usually has its first onset in elderly individuals
(causes have not yet been explained in detail in this type)

GLUCONEOGENESIS

Gluconeogenesis in the liver (major

site) and kidney (small amount)
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.

Reciprocal Regulation
of Gluconeogenesis
and Glycolysis in the
Liver.

Glycerol may enter either the gluconeogenic or the glycolytic

pathway at dihydroxyacetone phosphate.

Cooperation between Glycolysis and Gluconeogenesis

THE CONCENTRATION OF BLOOD GLUCOSE IS

REGULATED WITHIN NARROW LIMITS
postabsorptive state
blood glucose = between 4.5 and 5.5 mmol/L.
after a carbohydrate meal = rise to 6.57.2 mmol/L
starvation = fall to 3.33.9 mmol/L
insulin overdose
sudden decrease in blood glucose
convulsions
(immediate dependence of the brain for glucose)

BLOOD GLUCOSE IS DERIVED FROM :

THE DIET
GLUCONEOGENESIS,
GLYCOGENOLYSIS

The lactic acid (Cori) cycle and glucosealanine cycle

Metabolic Interchanges between Muscle and Liver

Glucose transporters

Insulin Plays a Central Role in

Regulating Blood Glucose
hyperglycemia

(B islet cells)

glucose

insulin

GLUT 2 transporter

glucose

glycolysis
the citric acid cycle

[ATP]
inhibits ATP-sensitive K+ channels
depolarization of the B cell membrane
voltage-sensitive Ca2+ channels

exocytosis of insulin
amino acids
free fatty acids
ketone bodies
glucagon
secretin
sulfonylurea drugs
tolbutamide
glyburide.

increases Ca2+ influx

The Bodys Ability to Utilize Glucose May Be Ascertained by

Measuring Its Glucose Tolerance

The Pentose Phosphate Pathway

two major functions:
(1) The formation of NADPH for synthesis of fatty
acids and steroids.
(2) the synthesis of ribose for nucleotide and nucleic
acid formation.
(No ATP is generated in the pentose phosphate pathway)

THE PENTOSE PHOSPHATE PATHWAY

GENERATES NADPH & RIBOSE PHOSPHATE
CYTOSOL

The Oxidative Phase Generates NADPH

The Nonoxidative
Phase Generates
Ribose Precursors

PPP
The pathway consists of
(1) an oxidative phase
that generates NADPH
and (2) a nonoxidative
phase that interconverts
phosphorylated sugars.

Regulation of the Pentose Phosphate Pathway

The dehydrogenation of glucose 6phosphate is the committed step in

the pentose phosphate pathway.

Role of the PPP in the glutathione peroxidase reaction

of erythrocytes
PPP & GLUTATHIONE PEROXIDASE PROTECT
ERYTHROCYTES HEMOLYSIS

A major cause of hemolysis of red blood cells, resulting in

hemolytic anemia Genetic deficiency of glucose 6-phosphate
dehydrogenase (G6PD).

Tissues with active pentose phosphate pathways

URONIC ACID PATHWAY

BLOCK IN PRIMATES
AND GUINEA PIGS
2-Keto-L-gulonolactone

L-Gulonolactone
O2

D-Glucuronate

L-Gulonate

Metabolism of fructose

(A) Conversion of Galactose to Glucose in the Liver

(B) Glucose to Lactose in the Lactating Mammary Gland