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Chapter 3
Carbohydrates

Carbohydrates
• Most abundant of the organic molecules
• Functions:
• Calories
• Energy storage
• Cell signaling [C(H2O)]n
• Structural components

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Biochemistry of Carbohydrates
• Carbohydrates can be classified using four
criteria:
• The number of carbons in the chain
• The size of the carbon chain
• The location of the carbonyl (CO) group
• Stereoisomers

Carbohydrates Carbonyl carbon

• Aldehydes or ketones

• C=O at the end of the carbon

chain = aldose

• C=O at an internal carbon =

ketose

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Cyclation
• Ring – predominate form
• Carbonyl carbon reacts with hydroxyl group – anomeric carbon

Monosaccharides
• Simple sugars that cannot be
hydrolyzed into a simpler form.

• Contain 3, 4, 5, 6 or more carbons.

• The most abundant and important: D-

glucose

• Others: fructose, galactose

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Disaccharides
• Consist of two monosaccharides joined by a covalent bond.

Lactose = glucose + galactose

Sucrose = glucose + fructose

Maltose = glucose + glucose

• Glycosyltransferases – form bonds

• Disaccharides are broken down into monosaccharides in
mouth and small intestines - glycosidases

Oligosaccharides/Polysaccharides
• Oligosaccharides have 3-10 monosaccharide units (includes disaccharides)

• Polysaccharides have >10 monosaccharide units

• Starch (plants)
• Amylose – Unbranched
• Amylopectin - Branched
• Cellulose (plants)
• Glycogen (animals)

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Carbohydrate Metabolism
• Start: MOUTH via salivary amylase (S-AMY). Hydrolysis of starch into maltose and
other small polymers of glucose.
• -amylase inhibitors being investigated as a potential means to impede digestion of dietary starch and
combat the overweight and obesity problem
• Gastric secretions in stomach inhibit salivary amylase.
• Digestions continues in the small intestines via pancreatic amylase (P-AMY).
• Enzymes lining the small intestines further break down disaccharides into
monosaccharides (lactase, sucrase, maltase, alpha-dextrinase)
• Monosaccharides are directly absorbed into the blood stream via the intestines
and taken to the liver.

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Digestion
• Disaccharidases
• Digestion primarily
in microvilli of
enterocytes
• Lactase, sucrase,
maltase, isomaltase,
and trehalase

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Monosaccharide Transporters
• SGLT-1
• Glucose, Galactose
• Sodium gradient
• GLUT-5
• Fructose
• GLUT-2
• Transport to hepatic portal circulation

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Absorption, Transport, & Distribution

• Facilitative Transport
• Stored in liver (glycogen),
glucose also will enter
bloodstream
• Glucose transporters
• As glucose is highly polar,
transport system to get in and
out of cells must be used
• Utilize protein carriers called
glucose transporters or “GLUT”

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Absorption, Transport, & Distribution

• Insulin
• Role in cellular glucose
absorption
• Binds to membrane
receptor
• Stimulates GLUT4 to
move to membrane
• Maintenance of blood
glucose levels

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Glycemic Response to Carbohydrates

• Glycemic index
• Increase in blood glucose during 2-hour period after consumption of a certain
amount of CHO compared with equal CHO from reference food
• Glycemic load
• Considers quantity and quality of CHO in a food
• GI x g of CHO in 1 serving of food

GI is a ranking of carbohydrate foods from 0 to 100 based

on how quickly they raise our blood sugar levels.

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Glycemic Index - Foods

Developed By: Glycemic Index Research Unit

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HOW TO SWITCH TO LOW GI MEALS

Check where most of your

carbohydrates come from –
rice, noodles, breads,
cereals & potatoes. Aim to
swap the high GI foods with
low GI foods at every meal.

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Table 3-03a p79

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Definitions
• Decreasing glucose levels in blood:
• Glycolysis: The metabolism of glucose for the production of energy (ATP)
• Glycogenesis: The synthesis of glycogen from glucose for later use.

• Increasing glucose levels in blood:

• Gluconeogenesis: The formation of glucose from non-carbohydrate sources.
• Glycogenolysis: The breakdown of glycogen to glucose.

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Glycolysis

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Glycolysis
• Divided into three
stages involving 10
total steps
• Energy-investment
stage

• Lysis stage

• Energy-conserving
stage

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First Steps – Phosphorylation

and Isomerization
• Unable to cross
membranes
• Enzymes (Irreversible)
• Hexokinase (3 isotypes)
– in most tissues
• Glucokinase – liver,
pancreas
• Storage, insulin
secretion

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Glycolysis Overview
• Pyruvate
• High energy molecule, feeds into
TCA cycle
• ATP
• 2 used, 4 gained
• Net yield: 2 ATP
• NADH
• Aerobic: Net gain of 2 NADH, feeds
into Electron Transport Chain
(reducing power)
• Anaerobic: No net gain of NADH

• Regulation: Glucagon, Insulin

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Hypoglycemia
• DECREASED plasma glucose concentration.

• ~50-55 mg/dL observable symptoms appear.

• Sx: mental confusion, chills, rapid heartbeat, weakness, trembling, nausea,

lightheadedness, hunger.

• Degree of Sx can vary

• Severe hypoglycemia can lead to seizures, coma and death.

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Hyperglycemia
• Elevated Blood Glucose
• Diabetes Mellitus
• Type I
• Insulin dependent
• Type II
• Non-insulin dependent
• Type III
• Other causes elevated blood glucose (pancreatitis, drug therapy, etc.)
• Type IV
• Gestational

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Type I Diabetes
• Accounts for 10-20% of all diabetes.

• Commonly occurs in childhood and adolescence.

• Formerly “juvenile diabetes”

• Cause may be genetic, autoimmune or infection

(virus)

• Leads to the destruction of pancreatic β cells and

therefore decreased/lack of insulin.

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Type 1 Diabetes Mellitus

• Clinical manifestations
• Hyperglycemia
• 80% to 90% of the function of the insulin-secreting beta
cells in the islet of Langerhans is lost
• Polydipsia, polyuria, polyphagia, weight loss, and
fatigue
• Require insulin replacement
• Diabetic ketoacidosis

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Type II Diabetes
• Formerly “adult-onset” diabetes.

• Characterized by hyperglycemia due to an individual’s resistance to

insulin with an insulin secretory defect.

• Onset after 40 years of age and often in the obese.

• Symptoms usually milder with ketoacidosis seldom occuring.

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Chronic Complications of
Diabetes Mellitus
• Hyperglycemia and nonenzymatic glycosylation
• Hyperglycemia and the polyol pathway
– Sorbitol and fructose increase intracellular osmotic
pressure (attracts water, leading to cell injury)
– Evident in the eye lens, nerves, RBCs
• Microvascular disease
– Retinopathy
– Diabetic nephropathy

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Gestational Diabetes
• Occurs in which women without previously diagnosed
diabetes.

• Women exhibit hyperglycemia during pregnancy

(especially during third trimester).

• Fetal insulin secretion is therefore stimulated.

• At birth, glucose supply is abruptly cut off, leading to

severe hypoglycemia.

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Laboratory Assessment for DM

From Sunheimer & Graves, Clinical Laboratory Chemistry, 1st Ed.

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DM - Glycosylated Hemoglobin
• Proteins in the blood can undergo glycosylation.
• Attachment of sugars to protein chains.
• The glucose attaches non-enzymatically to hemoglobin to the N-terminus of
both β-chains.
• Hemoglobin A1c (HbA1c) is most commonly detected glycosylated Hb

• The rate of formation is proportional to plasma glucose levels.

• RBC lifespan ~120 days reflects avg blood glucose over previous 2-3 months.
• For pts with DM, want to keep <7%

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Integrated Metabolism in Tissues

• The hexosemonophosphate shunt (pentose phosphate pathway)
• Pentose phosphates
• Reduced cosubstrate NADPH
• Gluconeogenesis
• Synthesis of glucose from non-CHO
• Reversal of glycolytic pathway

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Regulation of Metabolism
• 4 mechanisms:
• Negative or positive modulation of allosteric enzymes
• Hormonal activation by covalent modification/induction
• Directional shifts in reactions
• Translocation of enzymes within cells

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Tricarboxylic Acid Cycle

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Overview
• Convergence of Glycolysis, Proteolysis,
and Lipolysis
• Mitochondria
• Main Products: NADH, FADH2
• Aerobic
• Circular - balanced
• Some components used in other reactions

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•Main products of the

TCA cycle:
–Reduced NADH
and FADH2
–2 ATP produced

All reactions that occur in the Krebs cycle

happen twice for each glucose molecule
because two pyruvates are formed during
glycolysis.

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Net Gain
• Two carbons enter (acetyl-CoA), two leave (CO2)
• Three NAD+ -> NADH
• One FAD -> FADH2
• One GTP

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Glycolysis, TCA
• Glucose (C6H12O6) – Energy Rich
• Donate electrons to coenzymes
• NAD+ + 2e- + H+ -> NADH
• FAD + 2e- + 2H+ -> FADH2
• Electrons passed through Electron Transport
Chain
• Creates electron gradient – Proton Motive Force
• Coupled to ATP generation – Oxidative
Phosphorylation
• End Products: CO2 and H2O

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Mitochondria
• Double membrane organelle in eukaryotes
• DNA (circular), ribosomes
• Membranes
• Outer – Porins – permeable
• Inner
• Impermeable – special carriers
• Cristae (increase surface area)
• ATP Synthesizing Complex
• Matrix – gel like solution
• Many of the enzymes, precursors for ATP

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Electron Transport Chain - Carriers

• Five Protein Complexes – I, II, III, IV, V
• Accept e-, donate to carriers
• Coenzyme Q
• Cytochrome c
• Final Carrier – O2
• Terminal Electron Acceptor

FMN = Flavin mononucleotide, FAD = Flavin adenine dinucleotide

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Cyto a + a3

FMN Cyto bc1

FAD

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Energy Yield per

Glucose Molecule

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Sweeteners
Natural and Artificial

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Sweeteners

• Sucrose--benchmark of all sweeteners

• Caloric content (4 kcals/gm)
• Consumption ranges: 14-48 lbs/yr per person

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Fructose
• 10% of calories
• Sucrose
• cleaved in the intestine -> fructose and glucose
• Free monosaccharide in many fruits, honey
• High-fructose corn syrup
• 55% fructose and 45% glucose
• Transport is not insulin dependent
• Does not ↑ insulin

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High Fructose Corn Syrup

• Addition of unnatural amounts of fructose
• Increased steatohepatitis
• Increased weight gain
• Increased intake associated with:
• Diabetes
• Heart disease
• Inflammation
• Gout

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Artificial Sweeteners
• General recognized as safe (GRAS)
• Safety studies
• Animal dosing irregularities
• Long-term/high exposure

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Trehalose
• Naturally occurring (extraction
required)
• Disaccharide – trehelase
• Lower glycemic index than sucrose
(slower metabolism)
• Purported health benefits:
• Lower glucose/insulin spikes
• Decreased steatohepatitis
• Antioxidant
• Improved brain function

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Different Strokes For Different Folks

• One size does not fit all with weight loss diets --- we need a variety of
approaches to combat the obesity epidemic.

• It is possible that lower carbohydrate diets may be more effective for

people with Metabolic Syndrome.1-2
1. Samaha FF, Iqbal N, Seshadri P, et al. N Engl J Med. May 22 2003; 348 (21): 2074-2081.
2. Eckel RH, Drazin B. J. Investigative Med. 51:Suppl. 2.2003; S383.

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Metabolic Syndrome
• Causes
• Aging
• Obesity (truncal)
• High salt intake
• Genetics
• Lack of exercise
• Diet

• Can you be a healthy weight and still have metabolic syndrome?

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Popular Low Carbohydrate Diets

•The Dr. Atkins Diet (Has four levels):
–Induction (<20 g of carbs)
–Ongoing Weight Loss (Typically 25-45 grams carbs)
–Premaintenance (Typically 30-60 grams carbs)
–Maintenance (Typically 40-100 grams carbs)

•Carbohydrate Addicts’ Diet

•Protein Power RDA Carbohydrates: 130 g

•Cyclic Ketogenic

•The Zone Diet (30-40-30)

•Neanderthin

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The Three Most Common Low Carb Diets

2001 Low Carbohydrate Weight Loss Diet Survey)*

100.0%

80.0%
N= 5177
60.0%

40.0%

20.0%

0.0%

Dr. Atkins Protein Power Carb. Addicts

*Segal-Isaacson CJ, Segal-Isaacson AE, Wylie-Rosett, J. The Journal of The American

Dietetic Association. 2002. 102: S45.

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Typical Macronutrient Profile of

Low Carbohydrate Diets
Nutrient Percentage of Calories
Carbohydrate: 5-25%
Protein: 25-35%
Fat: 55-65%
Alcohol: <5% (metabolized mostly as fat)

• Due to increased satiety, less food may be eaten. Carbohydrate

intake is reduced while fat and protein intake may only moderately
increase. Calories are often substantially reduced.

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Typical Low Carbohydrate Dinner

Food Portion Size Calories Carbs Fat Protein
(g) (g) (g)
Roast Chicken 1/4 Chicken 306 0 19 31

Green Beans 3/4 Cup 102 9 9 3

with Sunflower
Seeds and Olive
Oil
Green Salad 2 Cups with 74 4 4 2
with Italian 1 Tablespoons
Dressing
Diet Gelatin 1 Cup with 70 2 6 3
with Whipped 1 Tablespoon
Cream
TOTALS : 550 15 38 39

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Short-Term Weight Loss Studies

• Early studies comparing low carb to low fat diets often used caloric
levels of <1000 cal/day. These very low calorie studies did not
show a weight loss difference between diets.*

• Most comparison studies today are using diets with moderate

calorie deficits of 500-700 kcal/day.

• The carbohydrate intake in current studies is usually about that of

the Atkins “Induction” Diet (most strict level) and is generally 30
g/day.

*Yang MU, Van Itallie TB. J Clin Invest. Sep 1976;58(3):722-730.

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Weight Loss Results

From p. 2085 of Foster et al., 2003 NEJM.

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Lipid Profile Changes

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Summary
• Low carb diets consistently produced more weight loss that
did not control the calorie levels between diets.
• When caloric content is controlled, near equal weight loss
over time.
• Low-carb diets improved Triacylglycerol and HDL Levels
• Low-carb diets did not improve total cholesterol or LDL
• Conventional diets did show improvement in these levels

Take home message?

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