BIOCHEMISTRY | Glycolysis

Glycolysis

is the process of glucose oxidation with formation of energy in form of ATP molecules with or without oxygen

Anaerobic glycolysis

(type of glycolysis)

is seen in RBCs and the contracting skeletal muscle

10

how many reactions of glycolysis

2

1 mol of glucose = __ pyruvate

1. preparative phase - 2ATP used

2. ATP-generating phase - 4 ATP produced, 2 pyruvate, 2 NADH

2 phases of glycolysis

Hexokinases

(enzyme)

glucose to Glucose 6-phosphate

Glucose 6-phosphate

a precursor for almost every pathway that uses glucose: glycolysis, the pentose phosphate pathway, and glycogen synthesis

phospho-hexose isomerase

(enzyme)

Glucose 6-phosphate to Fructose 6-phosphate

Phosphoructokinase 1 (PFK1)

(enzyme)

Fructose 6-phosphate to Fructose 1,6 bisphosphate

Fructose 6-phosphate to Fructose 1,6 bisphosphate

committed step of the glycolysis pathway

Step 1: Conversion of Glucose to Glucose 6-phosphate (irreversible)

Step 3: Conversion of Fructose 6-phosphate to Fructose 1,6 bisphosphate (irreversible)

in preparative phase 2 ATP is utilized. what are the steps that uses ATP

aldolase

(enzyme)

fructose 1,6 biphosphate to DHAP and Glyceraldehyde 3-P

aldolase A

type of aldolase

(Fructose 1,6 bisphosphate aldolase): Occurs in most tissues

aldolase B

type of aldolase

(Fructose-1-phosphate aldolase): Occurs in liver and kidney (involved into fructose metabolism,

Aldolase C

type of aldolase

: occurs in brain

Glyceraldehyde 3-phosphate Dehydrogenase

(enzyme)

Glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate

Arsenate

inhibits the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate by mimicking phosphate in the reaction

phosphoglycerate kinase

(enzyme)

1,3-biphosphoglycerate to 3-Phosphoglycerate

Phosphoglycerate mutase

(enzyme)

3-Phosphoglycerate to 2-phosphoglycerate

Enolase

(enzyme)

2-phosphoglycerate to Phosphoenol Pyruvate (PEP)

Fluoride

enolase is inhibited by __________ (used in blood collection tubes for blood glucose estimations)

Pyruvate kinase (PK)

(enzyme)

PEP to Pyruvate (irreversible)

1. 1,3-biphosphoglycerate - 2-phosphoglycerate

2. PEP to pyruvate

steps wherein ATP are formed

G3P to 1,3 biphosphoglycerate

steps wherein NADH are formed

Acetyl CoA (for TCA)

if AEROBIC pyruvate is converted to

Lactate

RBC, lens and cornea of the eye, kidney medulla, testes and leukocytes

if ANAEROBIC pyruvate is converted to

mostly happens in?

1. alanine (alanine aminotransferase)

2. oxaloacetate (pyruvate carboxylase)

3. acetyl coA (PDH) 

enumerate fates of pyruvate

Bisphosphoglycerate mutase

In erythrocytes, the reaction catalyzed by phosphoglycerate kinase may be bypassed to some extent by the reaction of______________________________, which catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate                                                                        

2,3-bisphosphoglycerate (2,3BPG)

binds to hemoglobin, decreasing its affinity for oxygen, so making oxygen more readily available to tissues

Step 1: Conversion of Glucose to Glucose 6-phosphate (Hexokinases/Glucokinase)

Step 3: Conversion of Fructose 6-phosphate to Fructose 1,6 bisphosphate (Phosphoructokinase 1 (PFK1))

Step 10: Conversion of 2 molecules of Phosphoenol Pyruvate to 2 molecules of Pyruvate (Pyruvate kinase)

3 rate limiting steps in glycolysis

activated by: Pi

inhibited by:Glucose-6-phosphate

Hexokinases regulators

activated by:AMP and fructose 2,6-bisphosphate

inhibited by: ATP and citrate

Phosphofructokinase-1(PFK-1) regulators

PFK2

Fructose 2,6-bisP is synthesized by 

1. kinase domain (Fructose 6-Phosphate to Fructose 2,6-Bisphosphate)

2. phosphate domain (Fructose 2,6-Bisphosphate back to Fructose 6-Phosphate)

PFK2 is a bifunctional enzyme with two separate domains:

insulin/Glucagon

High_________________ ration leads to increased concentration of fructose-2-6-biphosphate

activated by: fructose 1,6-bisP

inihibited by: (through phosphorylation) ATP, alanine

Pyruvate Kinase regulators

Pyruvate kinase deficiency

An inherited deficiency (an autosomal recessive trait, affecting males and females approximately equally) in pyruvate kinase leads to hemolytic anemia (an anemia caused by the destruction of red blood cells

hemolytic anemia

pyruvate kinase deficiency also manifests what kind of anemia

2,3-bisphosphoglycerate (2,3-BPG)

hemolytic anemia can be bypassed by elevation in ______________________________ since binds to hemoglobin, decreasing its affinity for oxygen, so making oxygen more readily available to tissues

1. Anemia

2. no heinz bodies

3. High concentration of 2,3BFG decreases affinity of Hb to O2

clinical presentation of pyruvate kinase deficiency

Lactic Acidemia (Lactic Acidosis)

lactic acid accumulates in blood to levels that significantly affect the pH

NADH/NAD+

Lactic acidosis generally results from a greatly increased __________________ ratio in tissues

lactic acidemia

• consumption of large amounts of alcohol → rapidly oxidized in the liver and increases NADH levels

• Hypoxia in any tissue increases lactate production

• Electron-transport chain defects

• Mitochondrial disorders

• Pyruvate oxidation defects (PDH complex defects)

anaerobic glycolysis

Most cancer cells paradoxically use __________  glycolysis as the main source of ATP. The cancer cells are more susceptible to glucose deprivation compared with normal cells.