BIOCHEMISTRY | Pentose Phosphate Pathway

• Hexose monophosphate (HMP) shunt

• 6-phosphogluconate pathway/shunt

Alternative names for PPP

anabolic

anabolic or catabolic

HMP is primarily __________ pathway that utilizes 6 carbons of glucose

1. generate NADPH

2. generate ribose 5-P

3. metabolize dietary pentose

Main function of PPP

cellular: cytoplasm

tissues: 

1. rapidly dividing cells

2. tissues that actively synthesized

3. tissue exposed to oxygen

main location of PPP in cell and tissue

none, only NADPH

are there consumed or produced ATP in PPP?

3

how many irreversible steps in PPP

Glucose-6-phosphate

intermediate in Glycolysis, Gluconeogenesis, Glycogen pathways, monosaccharides pathway, and the Pentose Phosphate Pathway

1. oxidative phase (2 NADPH)

2. nonoxidative phase (ribulose 5-P)

phases of PPP

Glucose 6-Phosphate

enzyme

dehydrogenation of glucose 6-phosphate

activated by: increased demand for NADPH, high Insulin

inhibited by: NADPH

Glucose 6-Phosphate regulators

Gluconolactonase

enzyme

Hydrolysis of 6-phosphogluconolactone

6-Phosphogluconate dehydrogenase

enzyme

Formation of Ribulose 5-phosphate

1. Ribose 5-phosphate in rapidly dividing cells

2. Intermediates of glycolysis: in non-dividing cells

Ribulose 5-phosphate is converted mainly to:

Phosphopentose Isomerase

enzyme

ribulose 5-phosphate → ribose 5-phosphate

Epimerase

enzyme

ribulose 5-phosphate → xylulose 5-phosphate

Transketolase

transfers a keto-group. requires thiamine pyrophosphate (TPP) as a co-factor

Transaldolase

transfers aldehyde-group

1. Pyruvate Dehydrogenase - Vit B1 dependent

2. a-KG Dehydrogenase - Vit B1 dependent

3. BCKD

4. Transketolase

TPP dependent reax

Wernicke-Korsakoff Syndrome (WKS)

• is caused by thiamine deficiency

• usually due to alcoholism and malnutrition

Wernicke's encephalopathy

• severe acute deficiency. Triad of symptoms:

• Ocular disturbances (ophthalmoplegia, horizontal nystagmus),

• Changes in mental state (confusion), Unsteady stance and gait (ataxia).

Korsakoff's psychosis

• chronic neurologic sequel after Wernicke's

• Confabulation,

• Personality change,

• Encephalopathy.

wet beriberi, and dry beriberi

Thiamine deficiency (beriberi) - two main types:

Dry beriberi

Dry beriberi

Dry beriberi

• Difficulty in walking

• Tingling or loss of sensation (numbness) in hands and feet

• Loss of tendon reflexes

• Loss of muscle function or paralysis of the lower legs

• Mental confusion/speech difficulties

• Pain, Vomiting

• Involuntary eye movements (nystagmus)

Wet beriberi

• affects the heart and circulatory system

• Increased heart rate

• Vasodilation leading to decreased systemic vascular resistance, and high output cardiac failure

• Elevated jugular venous pressure

• Dyspnea on exertion

• Paroxysmal nocturnal dyspnea

• Peripheral edema (swelling of lower legs)

Glutathione (glutamylcysteinylglycine)

is one of the body's principal means of protecting against oxidative damage

Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency

• X-linked recessive (mainly affects males)

• In heterozygotes (female carriers) G6PD deficiency provides an advantage in survival - advantage

Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency

• Hemolytic anemia

• Heinz Bodies

• Bite cells

Heinz bodies

are clumps of denatured hemoglobin