Ergonomía, materialidad y adaptabilidad

In the diet carbohydrates are present as complex polysac- charides (starch, glycogen) and to a minor extent, as di- saccharides (sucrose and lactose). They are hydrolyzed to monosaccharide units in the gastrointestinal tract.

The process of digestion starts in the mouth. Steps are given in Table 3.1.

Table 3.1: Digestion of carbohydrate Enzyme Site of action Function

Salivary amylase Mouth Starch/Glycogen Maltose, oligosaccharides, isomaltose Pancreatic

amylase

Small intestine Oligosaccharides Maltose, isomaltose Disaccharidases Small intestine

Sucrase Lactase Maltase Isomaltase Sucrose Glucose + Fructose Lactose Glucose + Galactose Maltose Glucose Isomaltose Glucose

After digestion by the action of various enzymes, di- etary carbohydrates are released and absorbed as mono- saccharides, which are almost completely absorbed from the small intestine.

Amongst the various monosaccharides, galactose and glucose are absorbed from the small intestine very rapidly, by the active process, which is linked to the transport of sodium and requires energy, in the form of hydrolysis of a high energy phosphate bond of adenosine triphosphate (ATP). A sodium-dependent glucose transporter, called sodium glucose transporter or SGLT-1 (Table 3.2), binds both glucose and sodium at separate sites and transports them through the plasma membrane of the intestinal cells.

Clinical Correlation: Lactose Intolerance

It is a condition resulting from a deficiency of intestinal lac- tase so that the individual is unable to digest the milk sugar.

Table 3.2: Glucose transporters (GLT) Transporter Locations Properties

Glu T1 RBC, kidney, brain,

retina, placenta Glucose uptake in most of cells Glu T2 Intestine, liver, pancreas Glucose uptake in liver (low affinity) Glu T3 Neurons, brain High affinity, glucose

uptake in brain Glu T4 Skeletal, heart muscles,

adipose tissue Insulin-mediated glucose uptake Glu T5 Small intestine, sperms,

kidney Fructose transporter Glu T7 Liver endoplasmic

reticulum Glucose from ER to cytoplasm SGLT Intestine, kidney Cotransport from

lumen to cell

Lactase deficiency results in the accumulation of un- digested lactose. Lactose moves to the colon where its bacterial fermentation generates CO₂ and organic acids. The symptoms include abdominal cramps, diarrhea and flatulence. Secondary lactase deficiency may result from damage to villi caused by drugs, prolonged diarrhea and malnutrition. Cheese is well tolerated since lactose gets removed during manufacturing. The management strat- egy is to gradually increase the intake of milk products, to take them with other foods and to spread their intake over the day. ‘Acidophilus milk’, i.e. milk pretreated with the bacteria Lactobacillus acidophilus is commercially available.

GLYCOLYSIS (EMBDEN-MEYERHOF-

PARNAS PATHWAY)

Oxidation of glucose is known as glycolysis. Glucose is oxidized to either lactate or pyruvate. Under aerobic con- ditions, the dominant product in most tissues is pyruvate and the pathway is known as aerobic glycolysis. When oxygen is depleted, as for instance during prolonged vig- orous exercise, the dominant glycolytic product in many tissues is lactate and the process is known as anaerobic glycolysis (Tables 3.3 and 3.4).

The pathway of glycolysis can be seen as consisting of two separate phases. The first is the chemical priming phase requiring energy in the form of ATP, and the second is considered the energy-yielding phase. In the first phase, two equivalents of ATP are used to convert glucose to fruc- tose-1,6-bisphosphate (F1,6BP) (Fig. 3.8). In the second phase F1,6BP is degraded to pyruvate, with the production of four equivalents of ATP and two equivalents of nicotin- amide adenine dinucleotide (NADH) (refer Fig. 3.8).

Fig. 3.8: Glycolysis (ADP, adenosine diphosphate; ATP, adenosine

triphosphate; Pi, inorganic phosphate; DHAP, dihydroxyacetone phosphate; NAD, nicotinamide adenine dinucleotide).

Table 3.3: Energetics of aerobic glycolysis

Step ATP (used –) (produced +)

1 –1

3 –1

5—NADH to ETC to FAD = 2 step

5 (twice) 2 × 2 = +4 6 (twice) 1 × 2 = +2 9 (twice) 1 × 2 = +2

Net 6 ATP

Table 3.4: Energetics of anaerobic glycolysis

Step ATP (used –) (produced +)

1 –1

3 –1

5—NADH to pyruvic acid to lactic acid ETC not used 0

6 (twice) 1 × 2 = +2 9 (twice) 1 × 2 = +2

Net 2 ATP

Glycolysis step mnemonic

“Goodness Gracious Father Franklin Did Go By Picking

Pumpkins (to) PrEPare Pies”:

• Glucose • Glucose-6-P • Fructose-6-P • Fructose-1,6-diP • Dihydroxyacetone-P • Glyceraldehyde-P • 1,3-Biphosphoglycerate • 3-Phosphoglycerate • 2-Phosphoglycerate • Phosphoenolpyruvate (PEP) • Pyruvate

Glycolytic enzymes mnemonic

“High Profile People Act Too Glamorous, Posing Every Place”: • Hexokinase

• Phosphoglucose isomerase • Phosphofructokinase (PFK) • Aldolase

• Triose phosphate isomerase

• Glyceraldehyde-3-phosphate dehydrogenase • Phosphoglycerate mutase

• Enolase • Pyruvate kinase

Irreversible Enzymes of Glycolysis

The ‘irreversible’ enzymes of glycolysis are those that in- volve ATP.

Hexokinase

• Irreversible

• Uses 1 ATP per glucose

• Low km (high affinity for glucose)

• Hexokinase is in all cells, and its isozyme glucokinase (aka hexokinase IV) is found in the liver. Glucokinase has a higher Km

• Active after meals (high glucose concentration in liver) • Allosteric inhibition by product (glucose-6-phosphate).

Phosphofructokinase-1

• Irreversible

• Uses 1 ATP per glucose

• Major rate regulator: At this point, the product has to continue in glycolysis (glucose and glucose-6-phosphate

Chapter 3: Carbohydrates 21

can have other fats until this point, i.e. glycogen synthe- sis or pentose phosphate pathway)

• Allosteric regulation • Negative—ATP, citrate

• Positive—AMP, ADP, fructose-2,6-bisphosphate.

Pyruvate Kinase

1. Irreversible.

2. Makes 2 ATP per glucose (1 per PEP): Transfers phos- phoryl group from PEP to ADP, producing ATP. 3. Allosteric regulation: a. Negative: • ATP • Acetyl-CoA • Fatty acids • Alanine 2. b. Positive: • Fructose-1,6-bisphosphate.

Energy Yield from Glycolysis Net reaction: As given below:

Glucose + 2NAD+ _{+ 2 Pi + 2 ADP 2 pyruvate + 2ATP}

+ 2 NADH + 2H₂O

Regulation of Glycolysis

Regulatory mechanisms controlling glycolysis include al- losteric and covalent modification mechanisms.

Glycolysis is regulated reciprocally from gluconeogen- esis. Molecules, such as F2, 6BP, that turn on glycolysis, turn off gluconeogenesis. Conversely, acetyl-CoA turns on gluconeogenesis, but turns off glycolysis.

The principle enzymes of glycolysis involved in regu- lation are hexokinase (reaction 1), phosphofructokinase (reaction 3) and pyruvate kinase (reaction 10):

1. Hexokinase is allosterically inhibited by glucose- 6-phosphate. That is, the enzyme for first reaction of glycolysis is inhibited by the product of first reaction. As a result, glucose and ATP (in reactions 1 and 3) are not committed to glycolysis unless necessary.

2. Phosphofructokinase (PFK) is a major control point for glycolysis. The PFK is allosterically inhibited by ATP and citrate, allosterically activated by AMP, ADP and F2, 6BP. Thus, carbon movement through glycoly- sis is inhibited at PFK when the cell contains ample stores of ATP and oxidizible substrates. Additionally, PFK is activated by AMP and ADP because they indi- cate low levels of ATP in the cell. The F2,6BP is the ma- jor activator, though, because it reciprocally inhibits F1,6BP bisphosphatase, which is the gluconeogenic enzyme that catalyzes the reversal of this step.

3. Pyruvate kinase is allosterically inhibited by acetyl-CoA, ATP and alanine, allosterically activated by F1,6BP.