Introduction & Biomedical importance

Importance Glucose is the most important-CHO. Glucose is the major fuel to mammalian tissues and to the fetus. Glucose is converted to other CHO e.g. glycogen for storage, ribose in Nucleic acid (DNA, ATP, NAD), Galactose in Lactose of milk, and in combination with proteins to form glycoprotein in cell members. Diseases associated with carbohydrates include diabetes mellitus, galactosemia, glycogen storage diseases and Lactose intolerance.

Glycolysis Glucose is metabolized to pyruvate in all mammalian cytosolic part of the cell. Glycolysis can proceed aerobically anaerobically to give ATP to skeletal muscle. Conversely, heart muscle which is poorly adapted to hypoxic conditions, so under anaerobic it cause is ischemia.

Glycolysis cycle 1G molecule splits into 2x3C - pyruvates. ATP used per 1G = -2 ATP ATP produced 1G= +2 x 2 = +4ATP NADH produced 1G= +2 x 3= +6 ATPs Net ATPS= 8ATPs

Control of Glycolysis By 3 irreversible reactions: A) HK B) PFK C) PK

INHIBITORS OF GLYCOLYSIS Iodoacitate. Arsenate. Flouride.

Oxidation of Pyruvate to Aetyl-coA Pyruvate + NAD + CoA pyruvate Dehydrogenase. Acetyl CoA + NADH + H + CO2 Acetyl CoA is point of entry into TCA cycle. Pyruvate dehydrogenase is inhibited by its end product acetyl CoA. 1 NADH ETC 3 ATP. 1 CO2 given off.

Anaerobic Glycolysis Glycolysis can proceed in the absence of oxygen, and end in lactate not pyruvate. When oxygen becomes available lactae is converted back to pruvate and pyruvate to acetyl-coA. In cancer cells, glycolysis proceeds much faster than TCA can utilize pyruvate. Pyruvate accumulation ending up in Lactate (anaerobic glycolysis). This acid environment which favors tumor growth. The Liver, kidney and heart take up Lactate and oxidize it but under hypoxic conditions they produce it.

Cori Cycle

Glycolysis in Erythrocytes Glycolysis in erythrocytes always terminate in Lactate because of lack of mitochondria. Produces less ATP, but synthesises 2,3,Biphosphoglycerate which is essential for releasing oxygen to the tissues – i.e. decreases the affinity of hemoglobin to oxygen. See next slide

Substrates for the TCA cycle is acetyl-coA sources which are: Fatty acids Amino acids Glucose They all give acetyl-coA.

TCA (Kreb’s) cycle TCA occur inside the mitochondrion. Oxaloacetate is driving force of cycle. 2 CO2 molecules released from one -2C acetyl CoA. 1 ATPs x 2= 2 ATPs produced per 1G. 3 NADH x 2= 6 NADH x 3 = 18 ATPs - per 1G. 1 FADH x 2= 2 FADH x 2= 4 ATPs - per 1G. G is completely oxidized.

3 Inhibitors: Fluoroacetate. Arsenate. Malonate (Competitive inhibition).