Carbohydrates metabolism Flashcards

(46 cards)

1
Q

steps of digestion of carbohydrates

A

(1) Digestion of carbohydrate in the form of starch or glycogen starts in
the mouth by action of salivary amylase that partially digests them
into dextrins and few moles of maltose.
(2) In the stomach no digestion occurs for carbohydrate due to gastric
acidity.
(3) In the small intestine pancreatic amylase completely digests starch
and glycogen into maltose.
(4) The brush border of intestinal mucosa secretes enzymes maltase,
lactase and sucrase that split the disaccharides as follows:
Maltose maltase
2 glucose
Lactose lactase
glucose and galactose
Sucrose sucrase
glucose and fructose

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2
Q

enumerate non digestible carbohydrates

A

They include the dietery cellulose,
hemicellulose and pectins which are made of glucose unites linked by β1,4 glucosidic linkage. In humans, there is no β-1-4 glucosidase that can
digest such bond

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3
Q

define lactose intolerance

A

This is a deficiency of lactase enzyme, present in brush border of
enterocytes, which digests lactose into glucose and galactose.
b) It may be:
i. Congenital that occurs very soon after birth (rare).
ii. Acquired that occurs later on life (common).

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3
Q

effects of lactose intolerance

A

he presence of lactose in intestine causes:
a) Increased osmotic pressure: Water will be drawn from the tissue
(causing dehydration) into the large intestine (causing diarrhea).
b) Increased fermentation of lactose by bacteria with subsequent
production of CO2 gas that causes distention & abdominal cramps.

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4
Q

inherited sucrase deficiency

A

This is a deficiency of sucrase enzyme, present in brush
border of enterocytes, which digests sucrose into glucose and fructose. It
occurs later after few months of birth when sucrose is added to infant diet.

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5
Q

effects of inherited sucrase deficiency

A

The presence of sucrose in intestine cause abdominal
distension and colic

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6
Q

fate of glucose in tissues

A
  1. Oxidation:
    a) Glycolysis followed by Kreb’s cycle are the major pathways.
    b) Pentose phosphate pathway and uronic acid pathway are minor
    pathways.
  2. Storage in the form of glycogen and fat.
  3. Conversion to substances of biological importance for e.g.
    a) Ribose, deoxyribose used for synthesis of RNA and DNA.
    b) Lactose of milk.
    c) Glucosamine and galactosamine of mucopolysaccharides.
    d) Glucuronic acid glycosaminoglycans and mucopolysaccharides.
    e) Fructose in semen.
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7
Q

Carriers of glucose

A
  • Uptake by liver: Glucose uptake is affected by GLUT 2 insulin
    independent transporters. Galactose and fructose are converted into
    glucose
  • Glucose uptake in adipose tissue and skeletal muscles is affected by
    GLUT 4 insulin dependent transporters.
  • RBCs use GLUT 1 transporters for glucose uptake. Glucose reaches
    brain cells through GLUT 3 insulin independent transpporters.
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8
Q

define glycolysis

A

Glycolysis means oxidation of glucose to give pyruvate (in
the presence of oxygen) or lactate (in the absence of oxygen) with net gain of
8 or 2 ATPs moles respectively.

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9
Q

Location of glycolysis

A
  1. Organ location: it ocurrs in all tissue cells, but it is of physiological importance
    in:
    ❖ Tissues with no mitochondria e.g., mature RBCs.
    ❖ Tissues with few mitochondria e.g., testes and leucocytes.
    ❖ Tissues that undergo frequent oxygen lack e.g., skeletal muscles especially
    during exercise.
  2. Cellular location: it ocurrs in the cytosol.
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10
Q

effects of pyruvate kinase deficiency

A

leads to hemolytic anemia

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11
Q

mention inhibtors of glyceraldehydye 3 - phosphate

A

Arsenate and iodoacetate

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12
Q

mention inhibitors of enolase enzyme

A

fluoride irreversibly inhibts enolase

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13
Q

Fate of pyruvate in aerobic conditions

A

In aerobic conditions: Under that condition pyruvate is transported from
cytoplasm into the mitochondria by symport mechanism involving one
proton which is co-transported. Inside the mitochondria, pyruvate acts as
substrate for two enzymes, pyruvate dehydrogenase complex and
pyruvate carboxylase producing acetyl CoA and oxaloacetate respectively
for Kreb’s cycle initiation.

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14
Q

fate of pyruvate in anaerobic conditions

A

In anaerobic conditions: Pyruvate is reduced to lactate-by-lactate
dehydrogenase enzyme (LDH) with reoxidation of NADH+H to NAD+
.
- Lactate formation is an obligatory end product of the glycolytic pathway in
red blood cells, parts of the retina, and in skeletal muscle cells during
strenuous exercise.

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15
Q

importance of lactate formation by lactate dehydrogenase from pyruvate

A

1-Under anaerobic conditions NADH is re-oxidized. This allows glycolysis
to proceed in the absence of oxygen. The process generates enough NAD
needed for glyceraldehyde 3- phosphate dehydrogenase for another cycle of
glycolysis.
2- Wash out excess pyruvate which cannot pass membranes

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16
Q

energy produced under anaerboic condition

A
  • 2ATPs are gained by substrate level phosphorylation via the reaction
    catalysed by 1,3 diphosphoglycerate kinase.
  • 2ATPs are gained at substrate level via the reaction catalyzed by
    pyurvate kinase
  • 2ATPs are lost for the phosphorylation of glucose by hexokinase
    enzymes and for phosphorylation of fructose 6-phosphate by
    phosphofructokinase -1.
  • 2ATPs are the net gain under anaerobic condition.
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17
Q

energy production under aerboic conditions

A
  • 2ATPs are gained at substrate level via reaction catalyzed by 1,3
    diphosphoglycerate kinase.
  • 2ATPs are gained at substrate level via reaction catalyzed by pyurvate
    kinase.
  • Shuttling of the two cysolic NADH+ +H+
    to the mitochondria and their
    subsequent oxidation via ETC will produce 6 or 4 ATP molecules if
    malate or glycerol phosphate shuttles are used respectively.
  • 2ATPs are lost for the phosphorylation of glucose and fructose-6-P
  • 8 or 6 molecules of ATPs are the net gain under aerobic condition
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18
Q

when does substrate level phosphrylation occur in glycolysis

A

Substrate Level Phosphorylation in glycolysis ocurrs at the level of:
** Phosphoglycerate kinase [1,3 bisphosphoglycerate to 3 phosphoglycerates]
** Pyruvate kinase [phosphoenol pyruvate to pyruvate].

19
Q

importance of glycolysis

A
  1. Important source of energy (8 ATPs or 2 ATPs under aerobic or
    anaerobic).
  2. It is the main route for glucose metabolism.
  3. It is an important metabolic pathway for fructose and galactose.
  4. It connects between carbohydrate, lipid and protein metabolism.
  5. Its reversibility is important for gluconeogenesis.
  6. Production of important metabolic intermediates e.g:
    * Dihydroxy acetone phosphate (DAHP) which gives glycerol 3-
    phosphate that is used for synthesis of triacylglycerol and phospholipids.
    * 3 phosphoglycerates can give serine.
20
Q

give an account of short term regulation of glycolytic pathway

A

1- Hexokinase is allosterically inhibited by glucose-6-P (feedback
inhibition).
2- Phosphofructokinase-1 is the rate limiting enzyme of glycolysis and is:
* Allosterically activated by AMP (low energy signal) & fructose 2,6
bisphosphate
* Allosterically inhibited by ATP and citrate (high energy signals).
{Pasteur effect}
3- Pyruvate kinase is:
* Allosterically activated by fructose 1,6 bisphosphate.
* Allosterically inhibited by ATP.
* Regulated by phosphorylation and dephosphorylation (covalent
modification). The active form is dephosphorylated.

21
Q

effect of fructose 2,6 biphosphate

A

Fructose 2,6 bisphosphate stimulates
glycolysis by allosteric stimulation of phosphofructokinase-1. It also inhibits
gluconeogenesis by inhibiting fructose 1,6 bisphosphatase enzyme. This
substrate is produced from fructose-6-phosphate by phosphofructokinase-2
(PFK-2). This enzyme is a bifunctional enzyme that has two catalytic sites;
one of them acts as a kinase that converts fructose-6-phosphate into
fructose 2,6 bisphosphate. The other acts as phosphatase converting
fructose 2,6 bisphosphate into fructose-6-phosphate.
* Insulin activates the kinase moity of the enzyme while the phosphatase
is activated by glucagon.

22
Q

define pasteur effect

A

It means that aerobic oxidation of glucose via Kreb`s cycle inhibits the
anaerobic degradation of glucose via glycolysis and consequently
inhibiting phosphofructokinase-1 causing accumulation of G6P with
consequent allosetric inhibition of hexokinase. Low AMP level & high
citrte concenteration are the causes.

23
Q

give an account of long term regulation of glycolytic pathway ( effect of hormones )

A

a) Insulin:
It is secreted after meal in response to high blood glucose level. It
stimulates synthesis of all key enzymes of glycolysis except hexokinase
which is a constitutive enzyme.
Also, it stimulates pyruvate kinase by dephosphorylation.
b) Glucagon: It is secreted in response to low blood glucose level. It inhibits
the synthesis of all key enzymes of glycolysis except hexokinase. Also, it
inhibits pyruvate kinase by phosphorylation of the enzyme protein

24
importance of DPG cycle
* DPG Cycle Is Important For: i) Economy of cell energy. ii)It is the source of DPG which decreases the affinity of Hb to oxygen increasing oxygen release to tissues i.e., tissue oxygenation.
25
PDH enzyme complex location and structure
A) Location: PDH is located within the mitochondrial matrix. B) Structure: PDH complex is a multi-enzyme complex that contains 3 protein enzymes and 5 coenzymes (all are vitamin B complex derivatives) namely: 1) Thiamin pyrophosphate (TPP). 2) Lipoamide. 3) Coenzyme A (CoASH). 4) Flavin adenine dinucleotide (FAD). 5) Nicotinamide adenine dinucleotide (NAD+ )
26
inhibtors of pdh complex
Arsenate and iodoacetate
27
energy production from oxidative decarboxylation of pyruvate
Oxidative decarboxylation of pyruvate to acetyl CoA produces one molecule of NADH+H+ . This produces 3 ATP molecules through ETC.
28
importance of PDH complex
Glucose through this step is converted to acetyl CoA (committed and irreversible step towards complete oxidation of glucose) * Thiamine deficiency affects PDH, hence complete oxidation of glucose. * PDH defect can lead to Lactic Acidosis. * Fat cannot be converted to glucose because of the irreversible nature of PDH. * Acetyl CoA cannot be converted to glucose
29
causes and manifestations of lactic acidosis
Causes of Lactic acidosis : ❖Congenital deficiency of pyruvate dehydrogenase enzyme. This enzyme déficiency results in an inability to convert pyruvate to acetyl CoA, causing pyruvate to be shunted to lactic acid via lactate dehydrogenase. ❖Deficiency of thiamine (poor diet and alcoholism) Manifestations : Lactic acidosis and coma due to accumulation of lactate
30
carboxylation of pyruvate by pyruvate carboxylase to produce oxalacetate
- It is an example of CO2 fixation that needs biotin as a co-enzyme & ATP
31
define krebs cycle and location
Definition: It is the final common oxidative pathway that oxidizes acetyl CoA into CO2, H2O and energy. Location: All enzymes of citric acid cycle are located in the mitochondrial matrix except succinate dehydrogenae which is located on the inner mitochondrial membrane (complex II of respiratory chain).
32
mention irreversible enzymes of TCA cycle
Most TCA enzymes are reversible except for citrate synthase and αKetoglutarate dehydrogenase.
33
notes on TCA cycle
* Aconitase enzyme, which catalyzes conversion of citerate to isociterate, is inhibited by fluoroacetate, which in the form of fluoroacetyl COA that condenses with oxaloacetate forming fluorocitrate, the later inhibits aconitase preventing isocitrate synthesis & accumulation of citrate. * There are 3 isocitrate dehydrogenases; one is NAD specific present in mitochondria, the other two are NADP specific and found in mitochondria & cytosole. * Arsenate inhibits α-Ketoglutarate dehydrogenase complex blocking Kreb’s cycle. α-Ketoglutarate accumulates upon poisoning of the enzyme. * Addition of malonate or oxaloacetate inhibits succinate dehydrogenase competitively leading to succinate accumulation
34
energetics of citric acid cycle
1. Isocitate dehydrogenase produces 3ATP. 2. α-Ketoglutarate dehydrogenase produces 3ATP. 3. Succinate thiokinase produces one ATP at substrate level. 4. Succinate dehydrogenase produces 2ATP 5. Malate dehydrogenase produces 3ATP.
35
Role of vitamins in citric acid cycle
1- Niacin in the form of NAD that acts as a co-enzyme for isocitrate, α-ketoglutarate & malate dehydrogenases. 2- Riboflavin in the form of FAD that acts as a cofactor for αketoglutrate and for succinate dehydrogenases. 3- Thiamin pyrophosphate (TPP) and pantothenic acid in the form of COASH are needed as cofactors for α-ketoglutarte dehydrogenase enzyme complex
36
metabolic importance of citric acid cycle
1- It is the final common pathway for carbohydrate, lipid and protein metabolism. 2- It is the major energy source (except in cells with no mitochondria as RBCs). 3- It connects between carbohydrate, lipid and protein metabolism. 4- It is a major source of succinyl CoA which is important for hemoglobin synthesis, ketone bodies utilization and detoxication. 5- It is an amphibolic pathway i.e., the metabolites of TCA have more than one function and occur at the crossroads of catabolic and anabolic pathways. Therefore, citric acid cycle plays an important role in the process of gluconegenesis, transamination and lipogenesis.
37
discuss regulation of citric acid cycle
1- The respiratory control (availability of oxygen): It is the main regulatory mechanism. The activity of TCA depends on the activity of ETC which is dependent upon the availability of oxygen and ADP and the rate of ATP utilization. This affects TCA through regeneration of oxidized dehydrogenase co-factors as NAD and FAD. 2- Citric acid cycle can be also regulated at the level of individual enzymes: a. Control of Pyruvate dehydrogenase enzyme complex: 1- Allosteric regulation: - Activators: Pyruvate. - Inhibitors: Acetyl CoA & NADH+H+ (product inhibition). 2- Covalent modification: a. PDH exists in two forms: Phosphorylated (inactive form) and dephosphorylated (active form). b. Phosphorylation of pyruvate dehydrogenase occurs by Mg++ ATP dependent PDH kinase, which cause phosphorylation of serine residues of the enzyme and inactivate the PDH complex. c. PDH kinase is is activated by ATP, NADH and acetyl CoA and inhibited by dichloroacetic acid, pyruvate, NAD and ADP d. PDH is dephosphorylated by pyruvate dehydrogenase phosphatase, which is stimulated by Ca++, Mg++ and insulin b. Citrate synthase (in citric acid cycle proper) * It is stimulated by acetyl CoA, oxaloacetate, ADP and NAD+. * It is inhibited by long chain acyl CoA, citrate, succinyl CoA, ATP and NADH c. Isocitrate dehydrogenase is allosterically inhibited by ATP and NADH and activated by ADP & NAD. d. α-ketoglutarate dehydrogenase is similar to pyruvate dehydrogenase i.e., activated by ADP, NAD & inhibited with ATP, NADH & succinyl COA. e. Succinate dehydrogenase is comptetitively inhibited by malonate and also inhibited by oxaloacetate. The availability of oxaloacetate is controlled by malate dehydrogenase. Briefly, the main function of TCA is to supply the tissues with ATP. Therefore, high levels of ATP will inhibit the TCA and vice versa.
38
define gluconeogenesis
Gluconoegenesis is the process of formation of glucose or glycogen from non-carbohydrate precursors, such as glucogenic amino acids, pyruvate, lactate, glycerol and propionyl CoA. It occurs during fasting and starvation.
39
location of gluconeogenesis
1. Intracellular location: partly mitochondrial & partly cytoplasmic. 2. Organ location: mainly in the liver, and to a lesser extent in the kidney
40
substrates for gluconeogenesis
1-Lactate: Lactate which is formed in skeletal muscles and erythrocytes is transported to the liver where it reforms glucose. In the liver cell lactate dehydrogenase converts lactate to pyruvate. Pyruvate enters gluconeogenic pathway to form glucose (Cori's cycle) 2- Glucogenic Amino Acids: a) Glucogenic amino acids are (Alanine, glutamic acid, aspartic acid, etc). b) In starvation or DM, glucogenic amino acids are transaminated to the corresponding carbon skeletons. These then enter the TCA cycle & form oxaloacetate or pyruvate. c) Alanine released from the muscle is a major substrate d) Alanine is transported to liver, transaminated to pyruvate & converted to glucose. This glucose may again enter the glycolytic pathway to form pyruvate, which in turn, can be transaminated to alanine (alanine cycle). 3-Glycerol which is a product of lipolysis of TAG in adipose tissue metabolism is acted upon by glycerol kinase enzyme present in the liver & other tissues except adipose tissue and muscle. Glycerol 3-p formed is converted to DHAP. 3-Glycerol which is a product of lipolysis of TAG in adipose tissue metabolism is acted upon by glycerol kinase enzyme present in the liver & other tissues except adipose tissue and muscle. Glycerol 3-p formed is converted to DHAP.
41
regulation of gluconeogenesis
I. Long term regulation (at the level of gene expression) a) Hyperglycemic hormones e.g., glucocorticoids, glucagon and epinephrine stimulate synthesis of all key enzymes of gluconeogenesis. b) Insulin on the other hand is a hypoglycemic hormone that inhibits the gluconeogenic process by inhibiting phosphoenal pyruvate carboxykinase (PEPCK) at the level of gene transcription II. Short term regulation: a- Pyruvate Carboxylase: Acetyl CoA is an activator of pyruvate carboxylase so that generation of oxaloacetate is favored when acetyl CoA level is sufficiently high. b- Fructose-1,6-bisphosphatase: Citrate is an activator while fructose-2,6- bis-phosphate and AMP are inhibitors. All these three effectors have opposite effect on the phosphofructokinase-1 (PFK-1). c- ATP: Gluconeogenesis is enhanced by ATP
42
biomedical importance of gluconeogenesis
1-The process of gluconeogenesis is important for glucose supply to the body when carbohydrates are not available in the diet. 2- Continuous supply of glucose is especially important for: a) Nervous system. b) Erythrocytes. c) Skeletal muscle especially under anaerobic conditions d) Formation of lactose, the milk sugar, in mammary glands. e) Glucose is the only fuel for fetus. 3- When blood glucose level is decreased, there is brain dysfunction and severe hypoglycemic coma and death may occur. 4- Glucose is also important for maintaining citric acid cycle as it is the main source of pyruvate. 5- Gluconeogenic process is used to clear the body from lactate that is formed in skeletal muscle and erythrocytes (Cori,s cycle).
43
definition and location of glycogenensis
Definition: Glycogenesis is the process of formation of glycogen from glucose. B- Location: 1. Intracellular location: Cytosol. 2. Organ location: Mainly in liver and muscles, however all cells have the capability to store minimal amount of glycogen. A considerable amount is synthesized in kidney also
44
importance of glycogenesis
Glycogenesis is a very essential process since excess glucose is converted and stored as glycogen which could be utilized at the time of requirement.
45
substrates of glycogenesis
1. In liver: a) Blood glucose. b) other hexoses: fructose and galactose. c) Non-carbohydrate sources: glycerol and lactate. - These are converted first to glucose, then to glycogen. 2. In muscles: Blood glucose only.