Nutritional biochemistry-Nutrition and the Cells

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營養生化學(0070210)

Nutritional biochemistry

保健營養學系三年級

授課教師：保健營養學系趙振瑞(Jane Chao)教授

Tel: 2736-1661 ext.6548; E-mail: [email protected]

Nutrition and the Cells

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Learning Objectives

• Components of typical cells

(0.5 h)

• Cell structures and functions

(1 h)

• Metabolism in the organelles

(1 h)

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References

• Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism, 5th ed. Wadsworth: Belmont, 2009.

• Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism, 4th ed. Wadsworth: Belmont, 2005.

• Linder MC. Nutritional Biochemistry and Metabolism: with Clinical Applications, 2nd ed. Elsevier: New York, 1991.

• Pike RL, Brown ML. Nutrition: An Integrated Approach, 3rd ed. MacMillan Publishing Company: New York, 1984.

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Cell types

• mono

cellular organisms:

pro

karyotic cells

• multi

cellular organisms:

eu

karyotic cells

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5 Mitochondria Plasma membrane Glycogen Nuclear envelope Nucleus Rough endoplasmic reticulum Cisternae of endoplasmic reticulum Nucleolus Golgi apparatus Smooth endoplasmic reticulum Lysosome Lipid droplet Gropper et al. 2005

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Plasma membrane

• lipids

• proteins

• hold together by

non-covalent

interaction

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Membrane lipids

• phospholipids

phosphoglycerides

phosphingolipids (phosphate-containing

sphingolipids)

• cholesterol

http://kentsimmons.uwinnipeg.ca/cm1504/Image127.gif

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Phosphoglycerides

• phosphoglycerides

glycerol + 2 fatty acid chains + 1 phosphate group

• phosphate group links to

glycerol (phosphatidic acid)

ethanolamine (phosphatidylethanolamine) choline (phosphatidylcholine; lecithin)

serine (phosphatidylserine)

threonine (phosphatidylthreonine) inositol (phosphatidylinositol)

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Phosphoglycerides

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11 Wolfe 1993

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Phosphingolipids

• sphingolipids

built on a

sphingosine

backbone

• phosphate-containing sphingolipids

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choline Sphingolipids

sphingosine ceramide sphingomyelin

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14 A B C D

(27C)

slightly polar http://www.people.vcu.edu/~urdesai/ahlp.h1.gif

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Membrane proteins

• integral proteins

• peripheral proteins

http://tonga.usip.edu/gmoyna/biochem341/membrane.jpeg

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(IP)

(PP)

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PP

IP

IP IP

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18 Gropper et al. 2005

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19 simple diffusion channel diffusion facilitated diffusion active transport Gropper et al. 2005

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nuclear envelope

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centrifuge

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Functions of ER

• RER: protein synthesis in ribosomes • SER: lipid and lipoprotein synthesis

• SER in the skeletal muscles: sarcoplasmic reticulum calcium ATPase (or pump)

• SER in the liver: a system for detoxification and

metabolism of drugs

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23 Ribosome Cristae DNA Outer membrane Inner membrane Matrix space Respiratory stalks Gropper et al. 2005

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Reactions in mitochondrial matrix

• decarboxylation of pyruvate pyruvate acetyl CoA

• Krebs (tricarboxylic acid, TCA) cycle • transamination

• amino acid oxidation via TCA cycle • Urea cycle (beginning)

• NEAA synthesis

• fatty acid oxidation

fatty acid acetyl CoA • polyamine synthesis

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Reactions in mitochondrial inner

membrane

• respiration

• electron transport chain and oxidative

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26 β-oxidation glucose glycolysis matrix oxidative phosphorylation ATP synthase Gropper et al. 2005

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27 http://cellbio.utmb.edu/cellbio/mitochondria_1.htm

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Functions of Golgi apparatus

• package into zymogen granules

• carbohydrate group modification

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Functions of

lysosomes

_lysosomes

• abundant in macrophages and leukocytes

• present in greatest numbers in kidney cells

• contains hydrolytic enzymes

hydrolyze proteins, nucleic acids, polysaccharides, phospholipids

• bone resorption (mineral removal)

lysosomes of osteoclasts promote dissolution of minerals and digest collagen

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Dysfunctions of

lysosomes

_lysosomes

• Type II glycogen storage disease (Pompe’s disease) missing lysosomal hydrolase (α-glucosidase)

accumulation of glycogen in vacuoles

glycogen can not be mobilized for metabolism proteolytic destruction of muscles

• Rheumatoid arthritis

associated with incomplete cellular autolysis

failure of lysosomal enzymes to perform their function of digesting dead cells and debris

lysosomal enzymes released from cells of synovial lining infecting organisms to cause membrane and cartilage damage

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Functions of

peroxisomes

_peroxisomes

• contains catabolic oxidative enzymes

• absence of acid phosphatase (different from lysosomes)

• In plants and microorganisms: gluconeogenesis

• H₂O₂ metabolism

H₂O₂ H₂O + ½ O₂

• degradation of purines

urate oxidase, xanthine dehydrogenase • oxidation of ethanol (detoxification)

CH₃-CH₂-OH + NAD+ CH₃-CHO + NADH + H+ ethanol acetaldehyde

• β-oxidation of unsaturated fatty acids

catalase

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Functions of

peroxisomes

_peroxisomes

• deamination of D-amino acid

D-amino acid + H₂O

α-keto acid + H₂O₂

FAD FADH₂

D-amino acid oxidase

H₂O + ½ O₂

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Liver

• processor and distributor in metabolism

• primarily responsible for the synthesis of urea,

creatine, plasma proteins, triacylglycerol,

phospholipids, and bile acids

• Blood enters liver: 65~75% from

portal vein

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Functions of liver

1. Regulation of blood glucose level

maintenance of normal [blood glucose]

rate of glucose entry into blood ≈ rate of glucose withdrawal

withdraw glucose from the blood for synthesis of glycogen (glycogenesis) for storage

supply glucose derived from its readily available store of glycogen through glycogenolysis

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Functions of liver

• Postabsorptive state

maintain blood glucose concentration: 80~100 mg/dL by glycogenolysis and gluconeogenesis

i.e. overnight fasting glycogenolysis/gluconeogeneis (75% vs 25%)

blood glucose in normal individuals: 60~160 mg/dL (remain constant)

normal control of glycosylation to proteins: blood glucose < 180 mg/dL

normal brain function requires ~ 6 g glucose/h

which can be delivered only if arterial blood contains

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Glucose transporters (GLUT)

• GLUT-1~GLUT-13

• GLUT-1: in most tissues during gestation

• GLUT-2

: primarily in liver, intestine, and

kidney,

insulin-independent

• GLUT-3: in the intestine and neurons

• GLUT-4

: in

skeletal muscles

, heart, and

adipose tissue,

insulin-sensitive

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Functions of liver

2. Gluconeogenesis

in liver and kidney during fasting or heavy

exercise

when carbohydrate intake is limited and body

glycogen stores are depleted

sources: lactate

(60%), glucogenic amino acids

(25%), glycerol

(10%), pyruvate

(5%)

proves for recycling of lactate (Cori cycle) and

glycerol accumulated in muscles

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Gluconeogenesis

lactate pyruvate alanine glycerol

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• in skeletal muscles and adipose tissue:

∵ lack of glucose-6-phosphatase (G-6-Pase)

glucose-6-phosphate glucose

lactate glucose

gluconeogenesis G-6-Pase

Gluconeogenesis

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3. Cori cycle

• oxygen supply is limiting (exercising muscles)

• in the absence of mitochondria (in RBC)

(1)early 12-h fasting: between

liver

and

muscles

,

liver

and

RBC

(2)24~48-h fasting: between

liver

and

RBC

(3)pregnancy: between

liver

and

placenta

(4)heavy exercise: between

liver

and

muscles

Functions of liver

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Cori cycle

liver blood muscles lactate lactate

glucose glucose

gluconeogenesis

anaerobic glycolysis

lactate accumulation oxygen debt acidosis

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4. Alanine cycle (glucose-alanine shuttle)

• a mechanism for

skeletal muscle

to eliminate

nitrogen

while replenishing its energy supply

(1) fasting

(2) exercise

Functions of liver

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45 Skeletal muscles gluconeogenesis deamination urea cycle transamination glycolysis amino acid α-keto acid

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5. Ketogenesis

• as an important fuel for brain, heart, and

skeletal muscles

(1) starvation

(2) lack of carbohydrate (a very low

carbohydrate diet)

(3)diabetes

high rate of

fatty acid oxidation

(

↓

glucose ox.

)

accumulation of

acetyl CoA

(exceeds the

capacity of TCA cycle)

Functions of liver

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Functions of liver

• ketone bodies:

acetoacetate

β-hydroxybutyrate

acetone

• occurs in liver mitochondria

• ∵ fatty acids can not pass blood-brain barrier

to brain

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Functions of liver

• acetone is difficult to oxidize in vivo

• if ↑↑ acetoacetate formed is faster than it can

be oxidized

→ ↑ [ketone bodies] in the blood

→ ketonemia

• if blood level exceeds the renal threshold

→ ketone bodies (H₂O-soluble) are excreted in urine

→ ketonuria

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49 2 acetyl CoA thiolase CoASH _{HMG CoA} synthase HMG CoA lyase breathe out (sweet smell) nonenzymatic decarboxylation β-hydroxybutyrate dehydrogenase NADH+H+ NAD+ NADH+H+ NAD+

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Utilization of

ketone

_ketone

bodies

_bodies

in extrahepatic cells (brain, heart, and skeletal muscles):

β-hydroxybutyrate

dehydrogenase CoA transferase

thiolase

TCA cycle

NAD+ _NADH+H+

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Ketogenesis

cytoplasm

NADH+H+ _NAD+

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6. Plasma protein synthesis

• albumin 150~250 mg/kg bw is synthesized daily in

adult humans

• synthesis and release of one albumin: ~30 min

• during fasting and malnutrition: ↓ albumin synthesis

malnutrition children: 100~148 mg albumin/kg/d well nourished children: 222~233 mg albumin /kg/d

Functions of liver

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7. Creatine synthesis

• occurs in liver and kidney

• precursors: glycine, arginine, ornithine, methionine

• after synthesis, creatine is transported to muscles

• in muscles: creatine phosphocreatine

Functions of liver

creatine kinase

spontaneously creatinine

0.3~0.5% muscle mass (by wt) can not be metabolized and is excreted in urine

indicator of amount of existing muscle mass

creatinine clearance:

estimates kidney function

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54 liver creatine kinase phosphocreatine; creatine phosphate spontaneously muscles

excreted into urine

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8. Urea synthesis (detoxication)

• occurs in liver, kidney, intestine

• disposal of ammonia arising from deamination and

from absorbed ammonia synthesized by intestinal

bacteria from urea and other sources

• glutamine serves as a major transport form for amino groups from peripheral tissues to liver

Functions of liver

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ammonia

mitochondria

cytosol

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9. Plasma lipid synthesis

• fatty acid synthesis

• plasma triacylglycerol, phospholipids, lipoproteins

(VLDL, HDL)

Functions of liver

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10. Cholesterol synthesis and degradation

• synthesis occurs in liver, adrenal cortex, skin,

intestine, testis, aorta

• in cytoplasmic matrix

• rate-limiting enzyme: HMG CoA reductase

Functions of liver

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59 (2C) thiolase (4C) HMG CoA synthase (6C) HMG CoA reductase 2NADPH+2H+ 2NADP+ (6C) polar +CoASH

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11. Bile acid synthesis

• bile salts: promote solubilization of lipids and

lipid-soluble materials for absorption through mucosal membrane

• primary (including conjugated) and secondary bile

acids

Functions of liver

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12. Bile pigment formation

• derived from heme breakdown

degraded porphyrin ring

Functions of liver

biliverdin (dark green)

bilirubin (orange-yellow)

reduction

+ albumin

to liver for clearance

diglucuronide derivative

digestive tract

in bile

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Summary

• Functions of organelles in eukaryotic cells are

complicated.

• A variety of metabolic pathways occur in different

organelles.

• Liver is responsible for a variety of synthesis,