CHO metabolism PART 1 from P.121 to P.130

Where are absorbed monosaccharides transported via circulation?

They are transported via portal circulation to the liver.

What happens to pentoses in the body?

Pentoses are excreted in the urine as the body doesn't utilize them.

What is the fate of hexoses such as galactose, mannose, and fructose?

Hexoses are converted into glucose.

What are the three pathways that glucose can undergo?

1. Anabolic pathway (e.g., Glycogenesis and gluconeogenesis). 2. Catabolic pathway (e.g., Glycogenolysis and minor pathways for glucose oxidation like HMP and uronic acid pathway). 3. Amphibolic pathway, which is both anabolic and catabolic (e.g., Glycolysis and Krebs cycle).

What is glycolysis?

Glycolysis is the oxidation of glucose or glycogen into pyruvic acid.

Where does glycolysis occur?

It occurs in the cytoplasm of all tissues.

What happens in glycolysis in the presence of oxygen and mitochondria?

It leads to the production of pyruvic acid.

What occurs in glycolysis in the absence of oxygen and mitochondria?

It results in the production of lactic acid.

In which tissues is glycolysis of physiological importance?

Glycolysis is of physiological importance in muscle during exercise (due to lack of oxygen) and in tissues like R.B.Cs, retina (fovea centralis), cornea, and lenses (due to lack of mitochondria).

Why is the activation of glucose into glucose-6-phosphate considered irreversible?

This reaction is irreversible because glucose-6-phosphate is at a higher energy level than glucose, and the products as a whole are at a lower energy level than the reactants as a whole.

What enzymes catalyze this reaction?

This reaction is catalyzed by either glucokinase or hexokinase.

What is the site of Hexokinase?

Hexokinase is found in all tissues except the liver.

What is the substrate for Hexokinase?

Hexokinase primarily acts on hexoses, mainly glucose.

Describe the affinity of Hexokinase.

Hexokinase has a high affinity and can function even in low blood glucose concentrations, which is indicated by its low Km value.

Is Hexokinase inducible by insulin?

No, Hexokinase is not inducible by insulin, meaning its synthesis is not affected by insulin.

How is Hexokinase inhibited?

Hexokinase is allosterically inhibited by glucose-6-phosphate.

What is the primary function of Hexokinase?

Hexokinase provides glucose-6-phosphate for glycolysis, enabling the production of energy regardless of blood glucose concentration.

What is the site of action for glucokinase?

In the liver and pancreas.

What is the primary substrate for glucokinase?

Hexoses, mainly glucose.

Describe the affinity of glucokinase for glucose.

It has low affinity and primarily acts in the presence of high blood glucose concentrations, characterized by a high Km.

How is the synthesis of glucokinase regulated?

It is induced by feeding and insulin while it decreases during fasting and in cases of diabetes mellitus (D.M.).

How is glucokinase inhibited, and what doesn't affect it?

It is not affected by glucose-6-phosphate and is not inhibited by it.

What are the key functions of glucokinase?

It provides glucose-6-phosphate for both lipogenesis and glycogenesis. It also plays a crucial role in regulating blood glucose levels after a meal, helping remove excess blood glucose.

What catalyzes the conversion of glucose-6-P into Fructose-6-P?

Phospho-hexose isomerase (aldose-ketose isomerase).

On which form of glucose-6-P does phospho-hexose isomerase act?

It acts only on the α-anomer of glucose-6-P.

What catalyzes the conversion of fructose-6-P into fructose 1,6-diphosphate?

Phosphofructokinase-I (PFK-I).

Why is the conversion of fructose-6-P into fructose 1,6-diphosphate considered irreversible?

It is irreversible because fructose 1,6-diphosphate has a higher energy level than fructose-6-phosphate, and the products as a whole have lower energy than the reactants as a whole.

Where is Phosphofructokinase-II found, and what is its role?

Phosphofructokinase-II is found in the liver and converts fructose-6-P into fructose 2,6 diphosphate.

What enzyme catalyzes the cleavage of fructose 1,6-diphosphate into two phosphotrioses?

Aldolase A or B can catalyze this cleavage.

Which phosphotrioses are formed from the cleavage of fructose 1,6-diphosphate?

Dihydroxyacetone phosphate and glyceraldehyde-3-P are formed, and they are interconvertible by phosphotriose isomerase.

Where is Aldolase A found and on what substrate does it act?

Aldolase A is found in all tissues and acts on fructose 1,6-diphosphate.

Where is Aldolase B found and on what substrates does it act?

Aldolase B is found in the liver, intestine, and kidneys and acts on fructose 1-P and fructose 1,6-diphosphate.

What favors the formation of glyceraldehyde-3-P in glycolysis?

Withdrawal of glyceraldehyde-3-P into glycolysis favors the reaction in its formation.

What is the enzyme responsible for the conversion of two molecules of glyceraldehyde-3-P into two molecules of 1,3 diphosphoglycerate?

Glyceraldehyde-3-P dehydrogenase catalyzes this conversion.

What is the byproduct of this conversion?

The conversion of glyceraldehyde-3-P into 1,3 diphosphoglycerate produces two molecules of NADH.

What enzyme catalyzes the conversion of two molecules of 1,3 DPG into two molecules of 3-phosphoglycerate?

Phosphoglycerate kinase catalyzes this conversion.

What type of phosphorylation is exemplified by this reaction?

It is an example of substrate-level phosphorylation, where ATP is produced directly from ADP and the energy liberated from the hydrolysis of a high-energy bond in the substrate, without intermediates.

What enzyme catalyzes the conversion of two molecules of 3-phosphoglycerate into two molecules of 2-phosphoglycerate?

Phosphoglycerate mutase catalyzes this conversion.

What enzyme catalyzes the conversion of two molecules of 2-phosphoglycerate into two molecules of phosphoenol pyruvate?

Enolase catalyzes this conversion by removing a water molecule from 2-phosphoglycerate, resulting in the redistribution of energy within the molecule and the formation of a high-energy phosphate bond.

What enzyme catalyzes the conversion of two molecules of phosphoenol pyruvate into two molecules of enol pyruvate?

Pyruvate kinase catalyzes this conversion, using two molecules of water, one for each molecule.

Why is the conversion of phosphoenol pyruvate into enol pyruvate considered irreversible?

It is irreversible because phosphoenol pyruvate has a higher energy level than enol pyruvate, and the products as a whole have lower energy than the reactants as a whole. This reaction is another example of substrate-level phosphorylation.

How does enol pyruvate spontaneously convert into pyruvate?

Enol pyruvate spontaneously converts into pyruvate.

Under anaerobic conditions, what enzyme catalyzes the conversion of pyruvate into lactate, and why is this necessary?

Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate into lactate. This is necessary to re-oxidize NADH when oxygen is absent and mitochondria are not functioning.

Under aerobic conditions, where does pyruvate go, and what process does it undergo?

Under aerobic conditions, pyruvate enters the mitochondria, where it undergoes oxidative decarboxylation into acetyl CoA.

What happens to acetyl CoA after it is produced in the mitochondria during aerobic conditions?

Acetyl CoA enters the Krebs' cycle for further oxidation.

How are the 2 NADH molecules produced during glycolysis oxidized under aerobic conditions, and what is the ATP yield?

The 2 NADH molecules are oxidized through the mitochondrial respiratory chain, producing either 4 ATP (2 ATP per reduced NAD) or 6 ATP (3 ATP per reduced NAD), depending on the shuttle system used.

What are the shuttles of glycolysis, and why are they necessary?

The shuttles of glycolysis are mechanisms for oxidizing extramitochondrial NADH produced in the cytoplasm during glycolysis. They are necessary because NADH can't penetrate the mitochondrial membrane under aerobic conditions to be oxidatively phosphorylated by the mitochondrial respiratory chain for energy production.

How many types of shuttles are there in glycolysis?

There are two types of shuttles in glycolysis.

What is the first type of shuttle?

The first type of shuttle is the phosphoglycerate shuttle.

What is the second type of shuttle?

The second type of shuttle is the malate aspartate shuttle.

Where is the phosphoglycerate shuttle primarily found?

The phosphoglycerate shuttle is primarily found in muscles and nerves.

How many ATP molecules are produced as a result of the phosphoglycerate shuttle, and how is this achieved?

The phosphoglycerate shuttle produces 4 ATP (2 ATP per reduced NAD) by converting cytoplasmic NADH+H+ into FADH2 in the mitochondrial matrix. The oxidation of FADH2 in the mitochondrial respiratory chain produces 2 ATP for each NADH converted, resulting in a total of 4 ATP.

What is the process by which cytoplasmic NADH+H+ is converted into FADH2 in the mitochondrial matrix?

Cytoplasmic NADH+H+ is converted into FADH2 in the mitochondrial matrix.

How many ATP molecules are produced from 2 cytoplasmic NADH molecules through the phosphoglycerate shuttle?

2 cytoplasmic NADH molecules are converted into 2 mitochondrial FADH2 molecules, which ultimately produce 4 ATP (2 ATP per FADH2).

Where is the malate aspartate shuttle primarily found?

The malate aspartate shuttle is primarily found in the liver and heart.

How many ATP molecules are produced as a result of the malate aspartate shuttle, and how is this achieved?

The malate aspartate shuttle produces 6 ATP (3 ATP per reduced NAD). Cytoplasmic NADH+H+ remains unchanged when passing into the mitochondrial matrix. The oxidation of NADH in the mitochondrial respiratory chain produces 3 ATP for each NADH converted, resulting in a total of 6 ATP.

What happens to cytoplasmic NADH+H+ when it enters the mitochondrial matrix in the malate aspartate shuttle?

Cytoplasmic NADH+H+ remains unchanged when passing into the mitochondrial matrix in the malate aspartate shuttle.

How many ATP molecules are produced from 2 cytoplasmic NADH molecules through the malate aspartate shuttle?

2 cytoplasmic NADH molecules are converted into 2 mitochondrial NADH molecules, which ultimately produce 6 ATP (3 ATP per NADH).

Under anaerobic conditions, how many ATP molecules are produced and lost during glycolysis?

Anaerobic glycolysis produces 4 ATP and loses 2 ATP, resulting in a net gain of 2 ATP.

Under aerobic conditions, how many ATP molecules are produced and lost during glycolysis?

Aerobic glycolysis produces 8 or 10 ATP and loses 2 ATP, depending on the shuttle used for NADH oxidation, resulting in a net gain of 6 or 8 ATP.

How many ATP molecules are spent in the activation of glucose into glucose-6-P and the conversion of fructose-6-P into fructose diphosphate?

1 ATP is spent in the activation of glucose into glucose-6-P, and 1 ATP is spent in the conversion of fructose-6-P into fructose diphosphate.

What is the total ATP loss in glycolysis, and how is it calculated?

The total ATP loss in glycolysis is 2 ATP, which is calculated by subtracting the ATP spent in activation and conversion (2 ATP) from the ATP produced (4 ATP in anaerobic and 8 or 10 ATP in aerobic conditions).

What are the end products of aerobic glycolysis?

The end product of aerobic glycolysis is pyruvate.

What are the end products of anaerobic glycolysis?

The end product of anaerobic glycolysis is lactate.

Is pyruvate available to the TCA cycle in aerobic glycolysis?

Yes, pyruvate is available to the TCA cycle in aerobic glycolysis.

Is lactate available to the TCA cycle in anaerobic glycolysis?

No, lactate is not available to the TCA cycle in anaerobic glycolysis as it is a cytosolic substrate.

How is NAD regenerated in aerobic glycolysis?

In aerobic glycolysis, NAD is regenerated by mitochondrial respiratory chain oxidation.

How is NAD regenerated in anaerobic glycolysis?

In anaerobic glycolysis, NAD is regenerated by lactate formation.

How many ATP molecules are produced in aerobic glycolysis?

Aerobic glycolysis produces 6 or 8 ATP, depending on the shuttle used for NADH oxidation.

How many ATP molecules are produced in anaerobic glycolysis?

Anaerobic glycolysis produces 2 ATP.

What is the role of 2-deoxy glucose in the inhibition of glycolysis?

2-deoxy glucose inhibits glucokinase or hexokinase.

How does arsenate affect glycolysis, and what is the consequence?

Arsenate resembles inorganic phosphorus "Pi" and replaces it in the reaction catalyzed by glyceraldehyde-3-P dehydrogenase. This results in the formation of 1-arseno-3-phosphoglycerate, which rapidly decomposes into heat and 3-phosphoglycerate. Glycolysis continues in the presence of arsenate but with a loss of 2 ATP due to bypassing one of the two substrate-level phosphorylations.

What is the impact of iodoacetate on glycolysis?

Iodoacetate inhibits glyceraldehyde-3-P dehydrogenase.

How does fluoride influence glycolysis, and why is it used for accurate glucose measurement in a blood sample?

Fluoride inhibits enolase, which is a glycolytic enzyme. It is used for the accurate measurement of glucose in a blood sample by fluorinating it to inhibit glycolysis in red blood cells (R.B.Cs).

Which enzyme catalyzes the conversion of glucose into glucose-6-P in glycolysis, and what is its function?

Enzyme: Glucokinase or hexokinase. Function: Catalyzes the conversion of glucose into glucose-6-P, initiating glycolysis.

Which enzyme catalyzes the conversion of fructose-6-P into fructose 1,6 diphosphate in glycolysis, and what is its function?

Enzyme: Phosphofructokinase-I (PFK-I). Function: Catalyzes the conversion of fructose-6-P into fructose 1,6 diphosphate, a key regulatory step in glycolysis.

Which enzyme catalyzes the conversion of phosphoenol pyruvate into enol pyruvate in glycolysis, and what is its function?

Enzyme: Pyruvate kinase. Function: Catalyzes the conversion of phosphoenol pyruvate into enol pyruvate, the final step in glycolysis, producing ATP.

What is the effect of insulin on the three key glycolytic enzymes?

Insulin activates the three enzymes: glucokinase/hexokinase, PFK-I, and pyruvate kinase.

What is the effect of glucagon on the three key glycolytic enzymes?

Glucagon inhibits the three enzymes: glucokinase/hexokinase, PFK-I, and pyruvate kinase.

What is the effect of adrenaline on glycolysis enzymes?

Adrenaline inhibits pyruvate kinase only.

What activates phosphofructokinase-I (PFK-I) and pyruvate kinase in terms of energy regulation?

High levels of ADP & AMP activate PFK-I and pyruvate kinase.

What inhibits phosphofructokinase-I (PFK-I) and pyruvate kinase in terms of energy regulation?

High levels of ATP inhibit PFK-I and pyruvate kinase.

What substrates activate glucokinase and hexokinase in terms of substrate regulation?

Glucose activates glucokinase, while glucose-6-P allosterically inhibits hexokinase.

What substrate inhibits phosphofructokinase-I (PFK-I) in terms of substrate regulation?

Citrate inhibits PFK-I.

What substrate activates pyruvate kinase in terms of substrate regulation?

Fructose 1,6 diphosphate activates pyruvate kinase.

What substrates inhibit pyruvate kinase in terms of substrate regulation?

Alanine, fatty acids, and acetyl CoA inhibit pyruvate kinase.

What substrate activates phosphofructokinase-I (PFK-I) in terms of substrate regulation?

Fructose 2,6 diphosphate activates PFK-I.

What is the major source of energy in certain tissues, such as R.B.Cs and muscles?

Glycolysis is the major source of energy in certain tissues, including R.B.Cs and muscles.

What does glycolysis produce that is essential for the Krebs' cycle?

Glycolysis produces pyruvic acid, which is needed for the Krebs' cycle.

What is the biochemical importance of the reversal of glycolysis?

The reversal of glycolysis is an essential source of glucose through gluconeogenesis.

How does glycolysis contribute to oxygen dissociation and tissue oxygenation, especially in cases of hypoxia?

Glycolysis produces 2,3 DPG (2,3-diphosphoglycerate), which decreases hemoglobin's affinity for oxygen, facilitating oxygen dissociation and tissue oxygenation, particularly in cases of hypoxia.

How does glycolysis link carbohydrate metabolism with amino acid metabolism?

Glycolysis links carbohydrate metabolism with amino acid metabolism through intermediates. For example, pyruvate is converted into alanine by transamination, and 3-phosphoglycerate is converted into serine.

What role does glycolysis play in linking carbohydrate metabolism with lipid metabolism?

Glycolysis provides dihydroxyacetone phosphate, a major source for glycerol-3-P needed for lipogenesis in adipose tissue.

What is the main pathway for the metabolism of fructose taken in the diet?

Glycolysis is the main pathway for the metabolism of fructose ingested in the diet.

How is glycolysis targeted in cancer therapy, and why is it effective for cancer cells?

Cancer therapy involves the administration or injection of inhibitors of glycolysis for cancer cells, which heavily rely on glycolysis as a major source of energy.

What are some genetic diseases resulting from deficiency in glycolytic enzyme activity, and how are they manifested?

A small number of genetic diseases result from deficiencies in glycolytic enzyme activity, such as hexokinase or pyruvate kinase deficiencies, which are manifested as hemolytic anemia.

What is the major source of energy in red blood cells (R.B.Cs), considering they lack mitochondria?

In R.B.Cs, anaerobic glycolysis is the major source of energy, and lactate is always the end product due to the absence of mitochondria.

Is glucose uptake by R.B.Cs dependent on insulin or blood glucose concentration?

No, glucose uptake by R.B.Cs is not dependent on insulin or blood glucose concentration.

What is the role of 2,3 DPG as a cofactor in glycolysis?

2,3 DPG serves as a cofactor for phosphoglycerate mutase, catalyzing the conversion of 3-phosphoglycerate to 2-phosphoglycerate.

Where is 2,3 DPG found in higher concentrations compared to other cells?

2,3 DPG is found in higher concentrations in red blood cells (R.B.Cs) compared to other cells, where it is present in traces.