Carbohydrates 1 & 2 Flashcards

1
Q

Describe the general structures and functions of carbohydrates and how they are digested and absorbed

A

General formula (CH2O) n
Can either be monosaccharides, disaccharides, oligosaccharides and polysaccharides.
They are the body’s primary source of energy
Breakdown of carbohydrates:
-Saliva contains amylase that breaks down starch and glycogen
-The pancreas contains amylase
-The small intestine contains disaccharidases attached to the brush border membrane of epithelial cells.

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2
Q

Explain the biochemical basis of lactose intolerance

A

Lactose intolerance is when too little of the enzyme that digests lactose is produced (lactase)
Primary lactase deficiency
Due to the absence of lactase persistence allele. It only occurs in adults and its highest prevalence is in Northwest Europe.
Secondary lactase deficiency
Cased by injury to the small intestine. Occurs in both infants and adults and is generally reversible.

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3
Q

Why can’t cellulose be digested in the GI tract

A

Cellulose is made up of beta glucose which are joined by 1-4 glycosidic bonds. Since the enzymes required to break down these bonds are not present in humans, we cannot breakdown cellulose.

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4
Q

Describe the glucose dependency of some tissues

A

All tissues can metabolise glucose, but some cells have an absolutes requirement such as red blood cells and the lens of the eye which lack mitochondria and the neutrophils which is in an environment where there is little/no oxygen.
The brain prefers to use glucose as a fuel but can use ketone bodies for some energy requirement in times of starvation but needs time to adapt.

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5
Q

Describe the key functions of glycolysis

A

-Oxidation of glucose
-NADH production (2 per glucose)
-Synthesis of ATP from ADP (2 net ATP per glucose)
-Provides biosynthetic precursors for FA, amino acids and nucleotides

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6
Q

Describe key features of glycolysis

A

-Central pathway of CHO catabolism
-Occurs in all tissues (cytosolic)
-Exergonic (energy producing), oxidative
-Irreversible pathway
-C6 —> 2C3 (No loss of CO2)
-With one additional enzyme (LDH) it is the only pathway that can operate anaerobically

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7
Q

Describe the key features of glycolysis and its control in muscles

A

Control of glycolysis in muscles
-One of the major functions of glycolysis is to generate ATP from ADP by phosphate level phosphorylation. Also, muscles contain myokinase that enables the high energy of hydrolysis phosphate bond in ADP to be used to drive ATP synthesis under emergency conditions
2 ADP <–> ATP + AMP
Therefore, it is appropriate for glycolysis to be
-inhibited when ATP is high and ADP + AMP is low
-Stimulated when ATP is low and ADP + AMP is high
This is because ATP is a high energy signal and ADP, and AMP are low energy signals

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8
Q

Explain how metabolic pathways are regulated

A

Some steps are reversible whilst some are irreversible. The irreversible steps are potential sites of regulation. Reduced activity reduces the flux of substrates through the pathway directly.
The most important rate limiting step is step 3 catalysed by the enzyme phosphofructokinase (PFK). PFK is subject to various forms of regulation including:
-Allosteric regulation (muscle) - inhibited by high ATP stimulated by high AMP
-Hormonal regulation (liver) - insulin stimulates and glucagon inhibits.

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9
Q

Explain the key role of pyruvate dehydrogenase in glucose metabolism

A

Pyruvate dehydrogenase connects the citric acid cycle and oxidative phosphorylation to glycolysis. Pyruvate dehydrogenase converts pyruvate to acetyl coA and increases the influx of acetyl coA from glycolysis into the TCA cycle.
In the mitochondrial matrix, (pyruvate from cytoplasm across mitochondrial membrane).
PDH is a large multi-enzyme complex.

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10
Q

Explain why lactate production is important in anaerobic glycolysis

A

When the supply of oxygen is inadequate and in cells without mitochondria, pyruvate is reduced to lactate, by lactate dehydrogenase
2 Pyruvate + 2 NADH –> 2 lactate + 2 NAD+
The NAD goes back into glycolysis and produces energy and the overall equation for anaerobic glycolysis is
Glucose + 2 pi + 2 ADP –> 2 lactate + 2 ATP + 2 H20

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11
Q

How is the blood concentration of lactate controlled

A

The lactate produced by tissues such as red blood cells (usually 50g), are released into the circulation and transported to the liver and heart muscle (and kidney) where it is converted back to pyruvate and oxidised to CO2 (heart muscle), or converted to glucose (liver and kidney)

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12
Q

Explain the biochemical basis of galactosaemia

A

Galactosaemia is when you are unable to utilise galactose. There are two types:
Galactokinase deficiency (rare) - galactose accumulates
Transferase deficiency (common) - galactose and galactose 1-P accumulate
This can be a problem as galactose enters other pathways such as aldose reductase where galactose is converted to Galactitol.

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13
Q

Explain the importance of the pentose phosphate pathway

A

Not all the glucose 6-phosphate produced in cells enters glycolysis, some is metabolised via the pentose phosphate pathway. This is an important pathway in tissues such as the liver, red blood cells, and adipose tissue. The major functions are to:
-Produce NADPH in the cytoplasm (NADPH has a number of functions such as provision of reducing power for anabolic processes, maintaining free -SH groups in red blood cells, involved in detoxification mechanisms that protects the cell against toxic chemicals).
-Produce the C5- sugar ribose for the synthesis of nucleotides. The pathway has high activity in dividing tissues.

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14
Q

Describe the clinical condition of glucose 6-phosphate dehydrogenase and explain the biochemical basis of the signs and symptoms.

A
  • X-linked gene defect caused by a mutation in the gene coding for glucose 6-phosphate dehydrogenase that results in reduced activity of the enzyme and therefore low levels of NADPH.
    Structural integrity and functions activity of some proteins depends on free -SH groups. Glutathione (GSH) protects cell from oxidative damage and in order to do this, NADPH is required to recycle GSH to its active reduced form. In G6PD deficiency, the NADPH levels are sometimes insufficient to prevent damage from occurring.
    Red blood cells are particularly affected as G6PDH in pentose pathway is only source of NADPH. Haemoglobin becomes cross-linked from oxidative damage and forms Heinz bodies. This leads to Haemolytic anaemia
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15
Q

What are the 3 enzymes involved in the initial stages of galactose metabolism

A
  • Galactokinase
  • Galactose 1 phosphate
  • UDP - galactose
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16
Q

What are the 2 key control enzymes in glycolysis

A

Hexokinase (glucokinase in liver) - Used in step 1 to catalyse the conversion of glucose to glucose 6-P
Phsphofructokinase-1 - Used in step 3 to catalyse the conversion of fructose 6-P to fructose 1,6 bis-P.
These 2 steps have large negative G so they are irreversible. Also step 3 is the first step that commits glucose to metabolism via glycolysis

17
Q

What are the metabolic consequences of an absence of galactose 1-P uridyl transferase

A

Accumulation of galactose 1-phosphate. Enters abnormal metabolic pathways. Causes irreversible damage to tissues. Interferes with ATP synthesis.

18
Q

What is Galactitol and how is it formed

A

Galactitol is formed when galactose enters a different pathway due to a build-up of galactose. The process in which Galactose is converted to Galactitol is known as aldose reductase

19
Q

Why do galactosaemic patients develop cataracts

A

The production of galactitol from aldose reductase also produces NADP+. This depletes the lens of NADPH, (which is an antioxidant), which causes the structure to be damages as thiol groups form disulphide bonds which is in the crystallin proteins in the lens. This cause folds in the proteins causing cataracts.

20
Q

Why is an absence of galactokinase less severe than an absence of galactose 1-P uridyl transferase.

A

It is less severe as only galactose is affected, whilst with an absence of galactose 1-P uridyl transferase, both galactose and galactose 1-P are affected.