BCH 202 Carbohydrate Metabolism Flashcards
The principal sites of carbohydrate digestion are the
mouth and the small intestine
Enzyme that begins digestion of starch in the mouth
salivary alpha amylase.
What are the enzymes that hydrolyze disaccharides into monosaccharides in the small intestine
sucrase, maltase, isomaltase and lactase.
What are the mechanisms of carbohydrate absorption?
•1. Active transport against a concentration gradient, i.e. from a low glucose concentration to a higher concentration.
•2. Facilitative transport, with concentration gradient i.e. from a higher concentration to a lower one.
The process of transport of carbohydrates is mediated by what?
Transporters
SGluT-1
SGluT-2
GLUT-1
GLUT-2
GLUT-4
Location and properties of SGlut
Intestine and kidney
Co-transport from lumen into cell
Location and properties of GLUT1
RBC, Kidney, brain, retina and placenta
Glucose uptake in most of the cells
Location and properties of GLUT2
Intestinal cells, liver, beta cells of the pancreas
Low affinity, glucose uptake in liver, glucose sensor in beta cells
Location and properties of GLUT3
Neurons, brain
High affinity, glucose into brain cells
Location and properties of GLUT4
Skeletal, heart
Insulin-mediated muscle, adipose tissue glucose uptake
How does insulin increase globose uptake
Insulin induces the movement of intracellular GluT4 molecules to the cell surface and thus increases glucose uptake.
How does type 2 diabetes mellitus affect absorption of glucose?
In type 2 diabetes mellitus, membrane GluT4 is reduced, leading to insulin resistance in muscle and fat cells. In diabetes, entry of glucose into muscle is only half of normal cells.
Normal fasting plasma glucose level
70-110mg/dl
plasma glucose level after a carb heavy meal
Under 150mg/dl
What is glycolysis?
Glycolysis is the sequence of reactions that converts glucose into pyruvate in the presence of oxygen (aerobic) or lactate in the absence of oxygen (anaerobic) with the production of ATP.
Glycolysis is also known as
Embden Meyerhof pathway.
Site of glycolysis reaction
Cytoplasm of cells
Enumerate the significance of glycolysis
It is the only pathway that is taking place in all the cells of the body
•Glycolysis is the only source of energy in erythrocytes
•The glycolytic pathway may be considered as the preliminary step before complete oxidation of glucose
•In strenuous exercise, when muscle tissue lacks enough oxygen, anaerobic glycolysis forms the major source of energy for muscles.
SGlut stands for
Sodium glucose link transporter
What is diabetes mellitus?
diabetes mellitus, disorder of carbohydrate metabolism characterized by impaired ability of the body to produce or respond to insulin and thereby maintain proper levels of sugar (glucose) in the blood.
Difference between hexokinase and glucokinase
Hexokinase
Present in extra-hepatic tissue
High affinity for its substrate glucose (low Km)
Inhibited by its product glucose-6-phosphate
Its function is to ensure supply of glucose for the tissues irrespective of blood glucose concentration
Its activity is not affected by insulin
Catalyze the phosphorylation of other hexoses like fructose galactose, etc.
Glucokinase
Present in liver
Low affinity for its substrate glucose (high Km)
No inhibition by its product glucose-6-phosphate
Its function is to remove glucose from the blood when the blood glucose level increases (following meal)
It is an inducible enzyme that increases its synthesis in response to insulin
Specific for glucose
Briefly describe the 9 stages of glycolysis
- Glucose is phosphorylated to glucose-6-phosphate by hexokinase or glucokinase and ATP is required as a phosphate donor. Hexokinase and glucokinase are isoenzymes.
- Conversion of glucose-6-phosphate to fructose-6-phosphate by an enzyme phosphohexose isomerase which involve isomerization and is freely reversible reaction.
- Fructose-6-phosphate to fructose 1, 6-bisphosphate, second phosphorylation reaction requiring ATP catalyzed by an enzyme phosphofructokinase-I. This step is irreversible under physiological conditions. Phosphofructokinase-I is regulatory enzyme of glycolysis.
- Fructose-1,6-bisphosphate is cleaved by aldolase to two three carbon compounds, glyceraldehyde-3-phosphate and dihydroxy acetone phosphate (DHAP)
DHAP is isomerized to glyceraldehyde-3-phosphate by the enzyme phosphotriose isomerase, so that, 2-molecules of glyceraldehyde-3-phosphate are formed from one molecule of glucose. - Oxidation of glyceraldehyde-3-phosphate to 1,3- bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase, is a NAD dependent reversible reaction. The reducing equivalents NADH+ H+ formed, are re-oxidized by electron transport chain, to generate 3 ATP molecules per NADH+H+.
- 1,3-bisphosphoglycerate to 3-phosphoglycerate is catalyzed by phosphoglycerate kinase. This is the step in glycolysis that generates ATP at substrate level phosphorylation. Since two molecules of glyceraldehyde-3-phosphate are formed per molecule of glucose undergoing glycolysis, two molecules of ATP are generated at this stage per molecule of glucose.
- 3-phosphoglycerate to 2-phosphoglycerate is a reversible reaction catalyzed by phosphoglycerate mutase.
- 2-phosphoglycerate to phosphoenol pyruvate. This reaction is catalyzed by enolase. Enolase is inhibited by fluoride, a property that can be used
when it is required to prevent glycolysis in blood prior to the estimation of glucose. - Phosphoenol pyruvate to pyruvate is an irreversible reaction catalyzed by pyruvate kinase. This is the second step in glycolysis that generates ATP at substrate-level phosphorylation. Enol pyruvate formed in this reaction is converted spontaneously to the keto form of pyruvate.
Under aerobic condition, pyruvate is taken up into mitochondria and after conversion to acetyl-CoA, it is then oxidized to CO2 and H2O by citric acid cycle.
What is substrate-level phosphorylation?
Substrate level phosphorylation is a reaction process that involves the trapping of energy directly from the substrate, without the help of the complicated electron transport chain reactions. When energy is trapped by oxidation of reducing equivalents such as NADH, it is called oxidative phosphorylation.
Briefly describe Anaerobic glycolysis
In anaerobic condition, pyruvate is reduced to lactate by lactate dehydrogenase (LDH). LDH has 5 isoenzymes. The cardiac isoenzymes will be increased in myocardial infarction.
In red blood cells, there are no mitochondria. Hence RBCs derive energy only through glycolysis, where the end product is lactic acid.
Describe the lactic acid or Cori’s cycle
Carl Cori and Gerty Cori described this process for which they were awarded a nobel prize in 1947.
It is a process in which glucose is converted to lactate in the muscle and in the liver, this lactate is reconverted into glucose.
In an actively contracting muscle, pyruvate is reduced to lactic acid which may tend to accumulate in the muscle.
The muscle cramps often associated with strenuous muscular exercise are thought to be due to lactate accumulation.
To prevent the lactate accumulation, body utilizes Cori’s cycle. This lactic acid from muscle diffuses into the blood.
Lactate then reaches the liver, where it is oxidized to pyruvate. Thus , it is channeled to gluconeogenesis and then regenerated glucose can enter the blood and then muscle.
This is the explanation for oxygen debt after vigorous exercise.
Which enzymes regulate glycolysis?
Glycolysis is regulated at 3 steps which are irreversible.
These reactions are catalyzed by:
1. Hexokinase and glucokinase (step 1)
2. Phosphofructokinase-I (step 3)
3. Pyruvate kinase. (step 9)
What is the energy yield of glycolysis?
ATP -1 ATP
GTP - ATP
NADH - 2.5 ATP
FADH - 1.5 ATP
How much ATP is produced from glycolysis?
2 ATP
Describe the conversion of pyruvate to acetyl CoA under aerobic conditions
Under aerobic conditions, pyruvate is converted to acetyl-CoA which enters the TCA cycle to be oxidized to CO2 and H2O. ATP is generated. Glycolysis is taking place in cytoplasm, so pyruvate is generated in cytoplasm. This is immediately transported into the mitochondria by a pyruvate transporter.
Pyruvate is converted to acetyl CoA by oxidative decarboxylation. This step occurs only in mitochondria.
This is an irreversible reaction catalyzed by a multienzyme complex known as pyruvate dehydrogenase complex (PDH)
Coenzymes of PDH
- Thiamine pyrophosphate (TPP)
- Coenzyme A (CoA)
- FAD
- NAD+
- Lipoic acid or lipoamide
Apoenzymes of PDH
- Pyruvate dehydrogenase- It catalyses oxidative decarboxylation.
- Dihydrolipoyl transacetylase.
- Dihydrolipoyl dehydrogenase.
Significance of PDH reaction
Significance
The conversion of pyruvate to acetyl-CoA is a central step, linking the glycolytic pathway with citric acid cycle.
Acetyl-CoA is also an important precursor in fatty acid biosynthesis and cholesterol biosynthesis.
It is a completely irreversible step or process. There is no pathway in the body to circumvent this step. Glucose through this step is converted to acetyl- CoA from which fatty acids can be synthesized.
Pyruvate may be channeled back to glucose through gluconeogenesis. But when pyruvate becomes acetyl-CoA, it cannot go back. Thus, PDH step is the committed step towards oxidation of glucose.
The NADH generated in this reaction enters the electron transport chain to produce 2.5 ATP molecules.
What is the Citric Acid Cycle
The citric acid cycle is a series of reactions in mitochondria that brings about the catabolism of acetyl-CoA to CO2 and H2O with the generation of ATP (formulated into a cycle by Sir Hans Krebs)
It is also known as tricarboxylic acid or TCA cycle, due to the involvement of the tricarboxylates—citrate and isocitrate.
Why is oxaloacetate an important junction point in metabolism?
Oxaloacetate may be viewed as a catalyst which enters into the reaction, causes complete oxidation of acetyl-CoA and comes out of it without any change. Oxaloacetate is an important junction point in metabolism.
Functions of Citric Acid Cycle
It is the final common oxidative pathway that oxidizes acetyl-CoA to CO2.
It is the source of reduced coenzymes that provides the substrate for the respiratory chain.
It acts as a link between catabolic and anabolic pathways (amphibolic role)
It provides precursors for synthesis of amino acids and nucleotides.
Describe the Amphibolic and Anaplerotic Role of TCA Cycle
Amphibolic Role of TCA Cycle
All other pathways such as beta oxidation of fat or glycogen synthesis are either catabolic or anabolic.
But TCA is truly amphibolic meaning it is both catabolic and anabolic in nature paving way for both breaking down processes and building up processes.
Anaplerotic Role of Tricarboxylic Acid Cycle
The citric acid cycle acts as a source of precursors of biosynthetic pathways e.g. heme is synthesized from Succinyl-CoA and Aspartate from oxaloacetate.
Anaplerotic reactions are metabolic pathways used to replenish oxaloacetate in the citric acid cycle after it has been consumed. The purpose of these reactions is to maintain adequate levels of ATP so that cellular respiration can carry on uninterrupted.
Describe the regulation of TCA Cycle
Regulation of TCA Cycle
The citric acid cycle is regulated in three steps. These are catalyzed by:
1. Citrate synthase
2. Isocitrate dehydrogenase
3. α-ketoglutarate dehydrogenase.
The activities of these enzymes are dependent on the energy status of the cycle.
Excess of ATP, NADH and succinyl-CoA, which signals the high energy status of the cell, inhibits these enzymes.
A high level of ADP which signals the low energy status of the cell stimulates the operation of the cycle.
Total generation of ATP from glucose metabolism
32 ATP
What is nitrogen fixation?
Reduction of Nitrogen to ammonia
Catalyzed by nitrogenase by nitrogen fixing bacteria in the soil to nitrites and nitrates
Plants utilize nitrites and nitrates
Nitrites and nitrates are converted to amino acids by plants.
Dietary proteins are consumed by animals and humans.
What is nitrogen balance (positive and negative)?
Ingestion of nitrogen per day is balanced by the amount excreted, resulting in no net change in the amount of body nitrogen.
O Negative Nitrogen Balance: nitrogen excretion exceeds ingestion ….occurs during Starvation, senescence, and some diseases
O Positive Nitrogen Balance: occurs in children etc.
What is digestion?
Digestion is the breakdown of complex nutrients to simple and soluble components.
What are the stages of protein digestion?
Gastric
Pancreatic
Intestinal
Describe protein digestion in the mouth
No enzyme in the mouth participates in protein digestion.
Saliva lubricates the food for the action of proteases.
Enzymes involved in protein digestion
Enzymes involved in protein
digestion
O Proteases
i. Endopeptidase ii. Exopeptidase
* Endopeptidases degrade proteins by hydrolyzing internal peptide bond and liberate large peptide fragments e,g, pepsin, renin, elastase. chymotrypsin.
Exopeptidases hydrolyze one amino acid at
a time from the C-terminus of proteins
(carboxypeptidases) and N-terminus
(aminopeptidases)
Describe the action and activation of pepsin
It is secreted in its zymogen form as pepsinogen by the chief cells of the stomach
O Activated by H ions in the gastric juice.
O Autoactivation to pepsin
O Catalyze gastric digestion of proteins to large peptide fragments and peptones.
Gastric juice is made up of HCl and enzymes
O HCl……….denaturation of proteins …….preparation for hydrolysis by proteases.
O It is acid stable (pH-sensitive)
List some pancreatic proteases
O Trypsin
O Chymotrypsin
O Elastase
O Carboxypeptidase
What are pancreatic proteases
They are secreted in the pancreas but activated in the small intestine
O Trypsin, Chymotrypsin, Elastase
* It is secreted as their individual zymogens
* Optimally active at pH 8
O Carboxypeptidase (exopeptidase)
O It is secreted as procarboxypeptidase.
Optimally active at pH 8
What are small intestine peptidases?
Small intestine peptidases
O Amino peptidases
O Dipeptidases
These lack a zymogen form and optimally active at pH 8
O Final digestion to free AA and small peptides
